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1. Missing Values in Longitudinal Proteome Dynamics Studies: Making a Case for Data Multiple Imputation.

Author: Yan, Yu, Sankar, Baradwaj, Mirza, Bilal, Ng, Dominic, Pelletier, Alexander, Huang, Sarah, Wang, Wei, Watson, Karol, Wang, Ding, and Ping, Peipei
Subjects: data imputation, longitudinal data, multiple imputation, protein turnover rate, Humans, Proteome, Proteomics, Animals, Mice, Longitudinal Studies, Data Interpretation, Statistical
Abstract: Temporal proteomics data sets are often confounded by the challenges of missing values. These missing data points, in a time-series context, can lead to fluctuations in measurements or the omission of critical events, thus hindering the ability to fully comprehend the underlying biomedical processes. We introduce a Data Multiple Imputation (DMI) pipeline designed to address this challenge in temporal data set turnover rate quantifications, enabling robust downstream analysis to gain novel discoveries. To demonstrate its utility and generalizability, we applied this pipeline to two use cases: a murine cardiac temporal proteomics data set and a human plasma temporal proteomics data set, both aimed at examining protein turnover rates. This DMI pipeline significantly enhanced the detection of protein turnover rate in both data sets, and furthermore, the imputed data sets captured new representation of proteins, leading to an augmented view of biological pathways, protein complex dynamics, as well as biomarker-disease associations. Importantly, DMI exhibited superior performance in benchmark data sets compared to single imputation methods (DSI). In summary, we have demonstrated that this DMI pipeline is effective at overcoming challenges introduced by missing values in temporal proteome dynamics studies.
Published: 2024

2. Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation

Author: Goodman, Shaun G, Steg, Philippe Gabriel, Szarek, Michael, Bhatt, Deepak L, Bittner, Vera A, Diaz, Rafael, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Manvelian, Garen, Pordy, Robert, Poulouin, Yann, Stipek, Wanda, Garon, Genevieve, Schwartz, Gregory G, Steg, Ph Gabriel, Tricoci, Pierluigi, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Hanotin, Corinne, Lecorps, Guillaume, Moryusef, Angèle, Sasiela, William J, Tamby, Jean-François, Aylward, Philip E, Drexel, Heinz, Sinnaeve, Peter, Dilic, Mirza, Lopes, Renato D, Gotcheva, Nina N, Prieto, Juan-Carlos, Yong, Huo, López-Jaramillo, Patricio, Pećin, Ivan, Reiner, Zeljko, Ostadal, Petr, Poulsen, Steen Hvitfeldt, Viigimaa, Margus, Nieminen, Markku S, Danchin, Nicolas, Chumburidze, Vakhtang, Marx, Nikolaus, Liberopoulos, Evangelos, Valdovinos, Pablo Carlos Montenegro, Tse, Hung-Fat, Kiss, Robert Gabor, Xavier, Denis, Zahger, Doron, Valgimigli, Marco, Kimura, Takeshi, Kim, Hyo Soo, Kim, Sang-Hyun, Erglis, Andrejs, Laucevicius, Aleksandras, Kedev, Sasko, Yusoff, Khalid, López, Gabriel Arturo Ramos, Alings, Marco, Halvorsen, Sigrun, Flores, Roger M Correa, Sy, Rody G, Budaj, Andrzej, Morais, Joao, Dorobantu, Maria, Karpov, Yuri, Ristic, Arsen D, Chua, Terrance, Murin, Jan, Fras, Zlatko, Dalby, Anthony J, Tuñón, José, de Silva, H Asita, Hagström, Emil, Landmesser, Ulf, Chiang, Chern-En, Sritara, Piyamitr, Guneri, Sema, Parkhomenko, Alexander, Ray, Kausik K, Moriarty, Patrick M, Chaitman, Bernard, Kelsey, Sheryl F, Olsson, Anders G, and Rouleau, Jean-Lucien
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Patient Safety, Clinical Research, 6.1 Pharmaceuticals, Good Health and Well Being, Humans, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents, Biomarkers, Cardiovascular Diseases, Cholesterol, LDL, Dyslipidemias, PCSK9 Inhibitors, Proprotein Convertase 9, Randomized Controlled Trials as Topic, Serine Proteinase Inhibitors, Time Factors, Treatment Outcome, ODYSSEY OUTCOMES Investigators, Alirocumab, Cholesterol, PCSK9, Safety, Cardiorespiratory Medicine and Haematology, Pharmacology and Pharmaceutical Sciences, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences
Abstract: The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.
Published: 2024

3. Characterizing Multimorbidity Prevalence and Adverse Outcomes in Ethnically and Culturally Diverse Sub-Populations in India: Gaps, Opportunities, and Future Directions.

Author: Zanwar, Preeti, Taylor, Robyn, Hill-Jarrett, Tanisha, Tsoy, Elena, Flatt, Jason, Mirza, Zunera, Hill, Carl, and Perianayagam, Arokiasamy
Subjects: India, LASI, chronic disease, multimorbidity, non-communicable diseases (NCDs), older adults, Humans, Aged, Multimorbidity, Prevalence, Comorbidity, Chronic Disease, Aging, India
Abstract: India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority populations in the United States (U.S.); however, limited studies have attempted to characterize multimorbidity among older adult sub-populations residing in India. To address this gap, we conducted a narrative review of studies on multimorbidity using the data from the Longitudinal Aging Study of India (LASI), the largest nationally representative longitudinal survey study of adults in India. Our definition of multimorbidity was the presence of more than two conditions in the same person. Our findings, based on 15 reviewed studies, aim to (1) characterize the definition and measurement of multimorbidity and to ascertain its prevalence in ethnically and culturally diverse sub-populations in India; (2) identify adverse outcomes associated with multimorbidity in the Indian adult population; and (3) identify gaps, opportunities, and future directions.
Published: 2024

4. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid‐Induced Osteoporosis

Author: Humphrey, Mary Beth, Russell, Linda, Danila, Maria I, Fink, Howard A, Guyatt, Gordon, Cannon, Michael, Caplan, Liron, Gore, Sara, Grossman, Jennifer, Hansen, Karen E, Lane, Nancy E, S., Nina, Magrey, Marina, McAlindon, Tim, Robinson, Angela Byun, Saha, Sumona, Womack, Charles, Abdulhadi, Basma, Charles, Julia F, Cheah, Jonathan TL, Chou, Sharon, Goyal, Itivrita, Haseltine, Katherine, Jackson, Lesley, Mirza, Reza, Moledina, Iram, Punni, Emma, Rinden, Tim, Turgunbaev, Marat, Wysham, Katherine, Turner, Amy S, and Uhl, Stacey
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Osteoporosis, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Management of diseases and conditions, 7.3 Management and decision making, Musculoskeletal, Good Health and Well Being, Adult, Child, Humans, United States, Rheumatology, Glucocorticoids, Bone Density, Public Health and Health Services, Psychology, Clinical sciences, Allied health and rehabilitation science
Abstract: ObjectiveThe objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily.MethodsAn updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations.ResultsFor adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included.ConclusionThis guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.
Published: 2023

5. Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Author: Dagar, Gunjan, Gupta, Ashna, Masoodi, Tariq, Nisar, Sabah, Merhi, Maysolun, Hashem, Sheema, Chauhan, Ravi, Dagar, Manisha, Mirza, Sameer, Bagga, Puneet, Kumar, Rakesh, Akil, Ammira S Al-Shabeeb, Macha, Muzafar A, Haris, Mohammad, Uddin, Shahab, Singh, Mayank, and Bhat, Ajaz A
Subjects: Humans, Neoplasms, Multiple Myeloma, Hematologic Neoplasms, Antigens, Neoplasm, Immunotherapy, Adoptive, Artificial Intelligence, Tumor Microenvironment, Cell- and Tissue-Based Therapy, Receptors, Chimeric Antigen, Antigen escape, CAR-T cell therapy, Cytokine release syndrome, Hematological malignancy, Immunotherapy, Solid tumor, Tumor antigens, Lymphoma, Biotechnology, Immunization, Hematology, Vaccine Related, Cancer, Rare Diseases, Genetics, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Medical and Health Sciences, Immunology
Abstract: Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.
Published: 2023

6. Stability of the gut microbiota in persons with paediatric-onset multiple sclerosis and related demyelinating diseases

Author: Liang, Geoffrey, Zhu, Feng, Mirza, Ali I, Bar-Or, Amit, Bernstein, Charles N, Bonner, Christine, Forbes, Jessica D, Graham, Morag, Hart, Janace, Knox, Natalie C, Marrie, Ruth Ann, O’Mahony, Julia, Van Domselaar, Gary, Yeh, E Ann, Zhao, Yinshan, Banwell, Brenda, Waubant, Emmanuelle, Tremlett, Helen, and Network, the Canadian Paediatric Demyelinating Disease
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Autoimmune Disease, Multiple Sclerosis, Neurodegenerative, Child, Gastrointestinal Microbiome, Humans, Syndrome, Multiple sclerosis, demyelinating disease, gut microbiota, stability, paediatric, monophasic acquired demyelinating syndrome, Canadian Paediatric Demyelinating Disease Network, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract: ObjectiveExamine if the gut microbiota composition changes across repeated samples in paediatric-onset multiple sclerosis (MS) or monophasic-acquired demyelinating syndromes (monoADS).MethodsA total of 36 individuals (18 MS/18 monoADS) with ⩾2 stool samples were included. Stool sample-derived DNA was sequenced. Alpha/beta diversities and genus-level taxa were analysed.ResultsMean ages at first sample procurement (MS/monoADS) = 18.0/13.8 years. Median time (months) between first/second samples = 11.2 and second/third = 10.3. Alpha/beta diversities did not differ between stool samples (p > 0.09), while one genus - Solobacterium did (p = 0.001).ConclusionsThe gut microbiota composition in paediatric-onset MS and monoADS exhibited stability, suggesting that single stool sample procurement is a reasonable first approach.
Published: 2022

7. SARS-CoV-2 Testing in the Community: Testing Positive Samples with the TaqMan SARS-CoV-2 Mutation Panel To Find Variants in Real Time

Author: Ashford, Fiona, Best, Angus, Dunn, Steven J, Ahmed, Zahra, Siddiqui, Henna, Melville, Jordan, Wilkinson, Samuel, Mirza, Jeremy, Cumley, Nicola, Stockton, Joanne, Ferguson, Jack, Wheatley, Lucy, Ratcliffe, Elizabeth, Casey, Anna, Plant, Tim, Aggarwal, Dinesh, Blane, Beth, Brooks, Ellena, Carabelli, Alessandro M, Churcher, Carol M, Galai, Katerina, Girgis, Sophia T, Gupta, Ravi K, Hadjirin, Nazreen F, Leek, Danielle, Ludden, Catherine, McManus, Georgina M, Palmer, Sophie, Peacock, Sharon J, Smith, Kim S, Allara, Elias, Bibby, David, Bishop, Chloe, Bosworth, Andrew, Bradshaw, Daniel, Chalker, Vicki, Chand, Meera, Dabrera, Gavin, Ellaby, Nicholas, Gallagher, Eileen, Groves, Natalie, Harrison, Ian, Hartman, Hassan, Hopes, Richard, Hubb, Jonathan, Hutchings, Stephanie, Lackenby, Angie, Ledesma, Juan, Lee, David, Manesis, Nikos, Manso, Carmen, Mbisa, Tamyo, Miah, Shahjahan, Muir, Peter, Myers, Richard, Osman, Husam, Patel, Vineet, Pearson, Clare, Platt, Steven, Pymont, Hannah M, Ramsay, Mary, Robinson, Esther, Schaefer, Ulf, Thornton, Alicia, Twohig, Katherine A, Vipond, Ian B, Williams, David, Hamilton, William L, Warne, Ben, Aigrain, Louise, Alderton, Alex, Amato, Roberto, Ariani, Cristina V, Barrett, Jeff, Bassett, Andrew R, Beale, Mathew A, Beaver, Charlotte, Bellis, Katherine L, Betteridge, Emma, Bonfield, James, Bronner, Iraad F, Chapman, Michael HS, Danesh, John, Davies, Robert, Dorman, Matthew J, Drury, Eleanor, Durham, Jillian, Farr, Ben W, Foulser, Luke, Goncalves, Sonia, Goodwin, Scott, Gourtovaia, Marina, Harrison, Ewan M, Jackson, David K, James, Keith, Jamrozy, Dorota, Johnston, Ian, Kane, Leanne, Kay, Sally, and Keatley, Jon-Paul
Subjects: Human Genome, Prevention, Biodefense, Genetics, Lung, Vaccine Related, Emerging Infectious Diseases, Good Health and Well Being, COVID-19, COVID-19 Testing, Humans, Mutation, SARS-CoV-2, COVID-19 Genomics UK (COG-UK) Consortium, PCR, SNPs, genome sequencing, genotyping, real time, variants of concern, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract: Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, is an excellent complement to genome sequencing, and has real clinical health value potential, allowing laboratories to report and take action on variants of concern much more quickly.
Published: 2022

8. Metagenomic Analysis of the Pediatric-Onset Multiple Sclerosis Gut Microbiome

Author: Mirza, Ali I, Zhu, Feng, Knox, Natalie, Forbes, Jessica D, Van Domselaar, Gary, Bernstein, Charles N, Graham, Morag, Marrie, Ruth Ann, Hart, Janace, Yeh, E Ann, Arnold, Douglas L, Bar-Or, Amit, O'Mahony, Julia, Zhao, Yinshan, Hsiao, William, Banwell, Brenda, Waubant, Emmanuelle, and Tremlett, Helen
Subjects: Pediatric, Neurodegenerative, Clinical Research, Autoimmune Disease, Digestive Diseases, Neurosciences, Brain Disorders, Genetics, Multiple Sclerosis, Neurological, Adolescent, Adult, Canada, Child, Female, Gastrointestinal Microbiome, Humans, Young Adult, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: Background and objectivesLittle is known of the functional potential of the gut microbiome in pediatric-onset multiple sclerosis (MS). We performed metagenomic analyses using stool samples from individuals with pediatric-onset MS and unaffected controls.MethodsPersons ≤21 years old enrolled in the Canadian Pediatric Demyelinating Disease Network providing a stool sample were eligible. Twenty patients with MS (McDonald criteria) with symptom onset 0.20), but metabolic pathways, gene annotations, and microbial taxonomy did. Individuals with MS (vs controls) exhibited higher methanogenesis prevalence (odds ratio 10, p = 0.044) and Methanobrevibacter abundance (log2 fold change [LFC] 1.7, p = 0.0014), but lower homolactic fermentation abundance (LFC -0.48, p = 0.039). Differences by DMD status included lower phosphate butyryl transferase for DMD-naive vs exposed patients with MS (LFC -1.0, p = 0.033).DiscussionThe gut microbiome's functional potential and taxonomy differed between individuals with pediatric-onset MS vs controls, including higher prevalence of a methane-producing pathway from Archaea and depletion of the lactate fermentation pathway. DMD exposure was associated with butyrate-producing enzyme enrichment. Together these findings indicate that the gut microbiome of individuals with MS may have a disturbed functional potential.
Published: 2022

9. Multimodal assessment of sustained threat in adolescents with nonsuicidal self-injury.

Author: Başgöze, Zeynep, Mirza, Salahudeen, Silamongkol, Thanharat, Hill, Dawson, Falke, Conner, Thai, Michelle, Westlund Schreiner, Melinda, Parenteau, Anna, Roediger, Donovan, Hendrickson, Timothy, Mueller, Bryon, Fiecas, Mark, Klimes-Dougan, Bonnie, and Cullen, Kathryn
Subjects: RDoC, adolescents, nonsuicidal self-injury, sustained threat, Adolescent, Humans, Female, Cross-Sectional Studies, Self-Injurious Behavior, Suicide, Attempted, Amygdala, Hydrocortisone
Abstract: Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala-mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala-mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.
Published: 2021

10. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

Author: Fraenkel, Liana, Bathon, Joan M, England, Bryant R, St.Clair, E William, Arayssi, Thurayya, Carandang, Kristine, Deane, Kevin D, Genovese, Mark, Huston, Kent Kwas, Kerr, Gail, Kremer, Joel, Nakamura, Mary C, Russell, Linda A, Singh, Jasvinder A, Smith, Benjamin J, Sparks, Jeffrey A, Venkatachalam, Shilpa, Weinblatt, Michael E, Al‐Gibbawi, Mounir, Baker, Joshua F, Barbour, Kamil E, Barton, Jennifer L, Cappelli, Laura, Chamseddine, Fatimah, George, Michael, Johnson, Sindhu R, Kahale, Lara, Karam, Basil S, Khamis, Assem M, Navarro-Millán, Iris, Mirza, Reza, Schwab, Pascale, Singh, Namrata, Turgunbaev, Marat, Turner, Amy S, Yaacoub, Sally, and Akl, Elie A
Subjects: Arthritis, Clinical Research, Management of diseases and conditions, 7.3 Management and decision making, Inflammatory and immune system, Good Health and Well Being, Antirheumatic Agents, Arthritis, Rheumatoid, Clinical Decision-Making, Consensus, Decision Support Techniques, Humans, Remission Induction, Rheumatology, Treatment Outcome, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: ObjectiveTo develop updated guidelines for the pharmacologic management of rheumatoid arthritis.MethodsWe developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.ResultsThe guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).ConclusionThis clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
Published: 2021

11. Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19.

Author: Shaefi, Shahzad, Brenner, Samantha, Gupta, Shruti, OGara, Brian, Krajewski, Megan, Charytan, David, Chaudhry, Sobaata, Mirza, Sara, Peev, Vasil, Anderson, Mark, Bansal, Anip, Hayek, Salim, Srivastava, Anand, Mathews, Kusum, Johns, Tanya, Leonberg-Yoo, Amanda, Green, Adam, Arunthamakun, Justin, Wille, Keith, Shaukat, Tanveer, Singh, Harkarandeep, Admon, Andrew, Semler, Matthew, Hernán, Miguel, Mueller, Ariel, Wang, Wei, and Leaf, David
Subjects: ARDS, COVID-19, Extracorporeal membrane oxygenation, Mortality, Severe respiratory failure, VV-ECMO, Adult, COVID-19, Cohort Studies, Extracorporeal Membrane Oxygenation, Female, Humans, Male, Middle Aged, Respiratory Distress Syndrome, Treatment Outcome
Abstract: PURPOSE: Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). METHODS: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2
Published: 2021

12. Association of low-frequency and rare coding variants with information processing speed

Author: Bressler, Jan, Davies, Gail, Smith, Albert V, Saba, Yasaman, Bis, Joshua C, Jian, Xueqiu, Hayward, Caroline, Yanek, Lisa, Smith, Jennifer A, Mirza, Saira S, Wang, Ruiqi, Adams, Hieab HH, Becker, Diane, Boerwinkle, Eric, Campbell, Archie, Cox, Simon R, Eiriksdottir, Gudny, Fawns-Ritchie, Chloe, Gottesman, Rebecca F, Grove, Megan L, Guo, Xiuqing, Hofer, Edith, Kardia, Sharon LR, Knol, Maria J, Koini, Marisa, Lopez, Oscar L, Marioni, Riccardo E, Nyquist, Paul, Pattie, Alison, Polasek, Ozren, Porteous, David J, Rudan, Igor, Satizabal, Claudia L, Schmidt, Helena, Schmidt, Reinhold, Sidney, Stephen, Simino, Jeannette, Smith, Blair H, Turner, Stephen T, van der Lee, Sven J, Ware, Erin B, Whitmer, Rachel A, Yaffe, Kristine, Yang, Qiong, Zhao, Wei, Gudnason, Vilmundur, Launer, Lenore J, Fitzpatrick, Annette L, Psaty, Bruce M, Fornage, Myriam, Arfan Ikram, M, van Duijn, Cornelia M, Seshadri, Sudha, Mosley, Thomas H, and Deary, Ian J
Subjects: Genetics, Brain Disorders, Aging, Human Genome, Adult, Cognition, Genome-Wide Association Study, Geroscience, Humans, Polymorphism, Single Nucleotide, Ubiquitin-Protein Ligases, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and clinical stroke. Linear regression models adjusted for age and gender were used for analysis of single genetic variants, and the T5, T1, and T01 burden tests that aggregate the number of rare alleles by gene were also applied. Secondary analyses included further adjustment for education. Meta-analyses to combine cohort-specific results were carried out separately for each ancestry group. Variants in RNF19A reached the threshold for statistical significance (p = 2.01 × 10-6) using the T01 test in individuals of European descent. RNF19A belongs to the class of E3 ubiquitin ligases that confer substrate specificity when proteins are ubiquitinated and targeted for degradation through the 26S proteasome. Variants in SLC22A7 and OR51A7 were suggestively associated with DSST scores after adjustment for education for African-American participants and in the European cohorts, respectively. Further functional characterization of its substrates will be required to confirm the role of RNF19A in cognitive function.
Published: 2021

13. Identifying temporal molecular signatures underlying cardiovascular diseases: A data science platform

Author: Chung, Neo Christopher, Choi, Howard, Wang, Ding, Mirza, Bilal, Pelletier, Alexander R, Sigdel, Dibakar, Wang, Wei, and Ping, Peipei
Subjects: Medical Biochemistry and Metabolomics, Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Heart Disease, Networking and Information Technology R&D (NITRD), Cardiovascular, Biotechnology, Human Genome, Bioengineering, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, Animals, Cardiovascular Diseases, Cluster Analysis, Cysteine, Data Science, Gene Expression Profiling, Humans, Protein Processing, Post-Translational, Time Factors, Temporal molecular signatures, Unsupervised clustering, Proteomics, Time-course, Data science, Oxidative post-translational modification, Cardiorespiratory Medicine and Haematology, Medical Physiology, Cardiovascular System & Hematology, Biochemistry and cell biology, Cardiovascular medicine and haematology, Medical physiology
Abstract: ObjectiveDuring cardiovascular disease progression, molecular systems of myocardium (e.g., a proteome) undergo diverse and distinct changes. Dynamic, temporally-regulated alterations of individual molecules underlie the collective response of the heart to pathological drivers and the ultimate development of pathogenesis. Advances in high-throughput omics technologies have enabled cost-effective, temporal profiling of targeted systems in animal models of human diseases. However, computational analysis of temporal patterns from omics data remains challenging. In particular, bioinformatic pipelines involving unsupervised statistical approaches to support cardiovascular investigations are lacking, which hinders one's ability to extract biomedical insights from these complex datasets.Approach and resultsWe developed a non-parametric data analysis platform to resolve computational challenges unique to temporal omics datasets. Our platform consists of three modules. Module I preprocesses the temporal data using either cubic splines or principal component analysis (PCA), and it simultaneously accomplishes the tasks on missing data imputation and denoising. Module II performs an unsupervised classification by K-means or hierarchical clustering. Module III evaluates and identifies biological entities (e.g., molecular events) that exhibit strong associations to specific temporal patterns. The jackstraw method for cluster membership has been applied to estimate p-values and posterior inclusion probabilities (PIPs), both of which guided feature selection. To demonstrate the utility of the analysis platform, we employed a temporal proteomics dataset that captured the proteome-wide dynamics of oxidative stress induced post-translational modifications (O-PTMs) in mouse hearts undergoing isoproterenol (ISO)-induced hypertrophy.ConclusionWe have created a platform, CV.Signature.TCP, to identify distinct temporal clusters in omics datasets. We presented a cardiovascular use case to demonstrate its utility in unveiling biological insights underlying O-PTM regulations in cardiac remodeling. This platform is implemented in an open source R package (https://github.com/UCLA-BD2K/CV.Signature.TCP).
Published: 2020

14. Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants

Author: Cunningham, Coleen K, McFarland, Elizabeth J, Morrison, R Leavitt, Capparelli, Edmund V, Safrit, Jeffrey T, Mofenson, Lynne M, Mathieson, Bonnie, Valentine, Megan E, Perlowski, Charlotte, Smith, Betsy, Hazra, Rohan, Purdue, Lynette, Muresan, Petronella, Harding, Paul A, Mbengeranwa, Tapiwa, Robinson, Lisa-Gaye, Wiznia, Andrew, Theron, Gerhard, Lin, Bob, Bailer, Robert T, Mascola, John R, Graham, Barney S, Aldrovandi, Grace, Bone, Frederic, Dayton, Dale, Johnston, Benjamin, Morgan, Patricia, Myers, Kathryn, Tobin, Nicole, Zimmer, Bonnie, Rossouw, Magdel, Rossouw, Lindie, Louw, Jeanne, Dobroszycki, Joanna, Burey, Marlene, Auguste, Raphaelle, Graham, Kathleen K, Major-Wilson, Hanna, Mhembere, Tsungai, Maturure, Sukunena, Bwakura-Dangarembizi, Mutsa, Barr, Emily, Dunn, Jennifer, Glenny, Carrie, Chambers, Carrie, Baig, Mahboobullah Mirza, Purswani, Murli, Deville, Jaime G, Nielsen-Saines, Karin, Shin, Christina, Carter, Michele F, Chahroudi, Ann, Ahonen, Alexis, Badell, Martina, Chakraborty, Rana, Agwu, Allison, Golden, W Christopher, Anderson, Thuy, Collinson-Streng, Aleisha, Diaz-Velasco, Rodrigo, Rosario, Nicolas, Pérez, Elvia, Marrero, Wanda I, Febo, Irma, Santos, Ruth, and Zorrilla, Carmen D
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Prevention, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric AIDS, HIV/AIDS, Pediatric, Clinical Research, Immunization, Vaccine Related, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Reproductive health and childbirth, Good Health and Well Being, Africa, Antibodies, Monoclonal, Broadly Neutralizing Antibodies, Female, HIV Antibodies, HIV Infections, HIV-1, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Injections, Subcutaneous, Linear Models, Male, United States, broadly neutralizing antibodies, mother-to-child transmission of HIV, neonates, VRC01, IMPAACT P1112 team, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundAlthough mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission.MethodsA Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis.ResultsForty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding.ConclusionsSubcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.
Published: 2020

15. Zika virus vertical transmission in children with confirmed antenatal exposure.

Author: Brasil, Patrícia, Vasconcelos, Zilton, Kerin, Tara, Gabaglia, Claudia Raja, Ribeiro, Ieda P, Bonaldo, Myrna C, Damasceno, Luana, Pone, Marcos V, Pone, Sheila, Zin, Andrea, Tsui, Irena, Adachi, Kristina, Pereira, Jose Paulo, Gaw, Stephanie L, Carvalho, Liege, Cunha, Denise C, Guida, Leticia, Rocha, Mirza, Cherry, James D, Wang, Lulan, Aliyari, Saba, Cheng, Genhong, Foo, Suan-Sin, Chen, Weiqiang, Jung, Jae, Brickley, Elizabeth, Moreira, Maria Elisabeth L, and Nielsen-Saines, Karin
Subjects: Humans, Communicable Diseases, Virus Diseases, Immunoglobulin M, Polymerase Chain Reaction, Pregnancy, Female, Zika Virus, Zika Virus Infection
Abstract: We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.
Published: 2020

16. α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

Author: Dodagatta-Marri, E, Meyer, DS, Reeves, MQ, Paniagua, R, To, MD, Binnewies, M, Broz, ML, Mori, H, Wu, D, Adoumie, M, Del Rosario, R, Li, O, Buchmann, T, Liang, B, Malato, J, Arce Vargus, F, Sheppard, D, Hann, BC, Mirza, A, Quezada, SA, Rosenblum, MD, Krummel, MF, Balmain, A, and Akhurst, RJ
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Cancer, Orphan Drug, Clinical Research, Immunization, Immunotherapy, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Antineoplastic Agents, Immunological, Biomarkers, CD4 Lymphocyte Count, Carcinoma, Squamous Cell, Cell Line, Tumor, Drug Synergism, Epithelial-Mesenchymal Transition, Humans, Immunohistochemistry, Lymphocyte Count, Lymphocytes, Tumor-Infiltrating, Programmed Cell Death 1 Receptor, Signal Transduction, Smad3 Protein, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Transforming Growth Factor beta, Checkpoint blockade, Squamous cell carcinoma, Tumor mutation load, -TGF, -PD-1 combinatorial immunotherapy, Tregs, pSmad signaling, Epithelial mesenchymal transition, α-TGFβ /α-PD-1 combinatorial immunotherapy, Oncology and carcinogenesis
Abstract: BackgroundCheckpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling.MethodsTo facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses.ResultsWe show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery.ConclusionsWe show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165).
Published: 2019

17. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, Claudia L, Adams, Hieab HH, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, and Schmidt, Helena
Subjects: Biological Sciences, Genetics, Brain Disorders, Mental Health, Neurosciences, Human Genome, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Animals, Brain, Cohort Studies, Drosophila melanogaster, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019

18. Machine Learning and Integrative Analysis of Biomedical Big Data.

Author: Mirza, Bilal, Wang, Wei, Wang, Jie, Choi, Howard, Chung, Neo Christopher, and Ping, Peipei
Subjects: Animals, Humans, Computational Biology, Machine Learning, Big Data, class imbalance, curse of dimensionality, data integration, heterogeneous data, machine learning, missing data, multi-omics, scalability, Genetics
Abstract: Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues.
Published: 2019

19. Integrated Dissection of Cysteine Oxidative Post-translational Modification Proteome During Cardiac Hypertrophy.

Author: Wang, Jie, Choi, Howard, Chung, Neo, Cao, Quan, Ng, Dominic, Mirza, Bilal, Scruggs, Sarah, Wang, Ding, Garlid, Anders, and Ping, Peipei
Subjects: biotin switch, cardiac hypertrophy, computational workflow, cubic spline, cysteine oxidative modification, redox proteomics, Calcium, Cardiomegaly, Creatine, Cysteine, Glucose, Humans, Oxidation-Reduction, Phosphorylation, Protein Processing, Post-Translational, Proteome, Time Factors
Abstract: Cysteine oxidative modification of cellular proteins is crucial for many aspects of cardiac hypertrophy development. However, integrated dissection of multiple types of cysteine oxidative post-translational modifications (O-PTM) of proteomes in cardiac hypertrophy is currently missing. Here we developed a novel discovery platform that encompasses a customized biotin switch-based quantitative proteomics pipeline and an advanced analytic workflow to comprehensively profile the landscape of cysteine O-PTM in an ISO-induced cardiac hypertrophy mouse model. Specifically, we identified a total of 1655 proteins containing 3324 oxidized cysteine sites by at least one of the following three modifications: reversible cysteine O-PTM, cysteine sulfinylation (CysSO2H), and cysteine sulfonylation (CysSO3H). Analyzing the hypertrophy signatures that are reproducibly discovered from this computational workflow unveiled four biological processes with increased cysteine O-PTM. Among them, protein phosphorylation, creatine metabolism, and response to elevated Ca2+ pathways exhibited an elevation of cysteine O-PTM in early stages, whereas glucose metabolism enzymes were increasingly modified in later stages, illustrating a temporal regulatory map in cardiac hypertrophy. Our cysteine O-PTM platform depicts a dynamic and integrated landscape of the cysteine oxidative proteome, through the extracted molecular signatures, and provides critical mechanistic insights in cardiac hypertrophy. Data are available via ProteomeXchange with identifier PXD010336.
Published: 2018

20. Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images.

Author: Lu, Donghuan, Popuri, Karteek, Ding, Gavin Weiguang, Balachandar, Rakesh, Beg, Mirza Faisal, and Alzheimer’s Disease Neuroimaging Initiative
Subjects: Alzheimer’s Disease Neuroimaging Initiative, Brain, Humans, Alzheimer Disease, Fluorodeoxyglucose F18, Radiopharmaceuticals, Positron-Emission Tomography, Magnetic Resonance Imaging, Early Diagnosis, Sensitivity and Specificity, Case-Control Studies, Aged, Aged, 80 and over, Middle Aged, Multimodal Imaging, Cognitive Dysfunction, Deep Learning, Neural Networks, Computer, Networking and Information Technology R&D, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Brain Disorders, Aging, Clinical Research, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease, Bioengineering, Neurodegenerative, Neurosciences, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Neurological
Abstract: Alzheimer's Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1-3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature.
Published: 2018

21. Understanding Disorder Within Variation: Production of English Grammatical Forms by English Language Learners

Author: Bedore, Lisa M, Peña, Elizabeth D, Anaya, Jissel B, Nieto, Ricardo, Lugo-Neris, Mirza J, and Baron, Alisa
Subjects: Allied Health and Rehabilitation Science, Education Systems, Health Sciences, Education, Pediatric, Clinical Research, Child, Child Language, Child, Preschool, Female, Hispanic or Latino, Humans, Language Development Disorders, Language Tests, Learning, Linguistics, Male, Multilingualism, Clinical Sciences, Specialist Studies in Education, Speech-Language Pathology & Audiology, Education systems, Allied health and rehabilitation science
Abstract: PurposeThis study examines English performance on a set of 11 grammatical forms in Spanish-English bilingual, school-age children in order to understand how item difficulty of grammatical constructions helps correctly classify language impairment (LI) from expected variability in second language acquisition when taking into account linguistic experience and exposure.MethodThree hundred seventy-eight children's scores on the Bilingual English-Spanish Assessment-Middle Extension (Peña, Bedore, Gutiérrez-Clellen, Iglesias, & Goldstein, 2008) morphosyntax cloze task were analyzed by bilingual experience groups (high Spanish experience, balanced English-Spanish experience, high English experience, ability (typically developing [TD] vs. LI), and grammatical form. Classification accuracy was calculated for the forms that best differentiated TD and LI groups.ResultsChildren with LI scored lower than TD children across all bilingual experience groups. There were differences by grammatical form across bilingual experience and ability groups. Children from high English experience and balanced English-Spanish experience groups could be accurately classified on the basis of all the English grammatical forms tested except for prepositions. For bilinguals with high Spanish experience, it was possible to rule out LI on the basis of grammatical production but not rule in LI.ConclusionsIt is possible to accurately identify LI in English language learners once they use English 40% of the time or more. However, for children with high Spanish experience, more information about development and patterns of impairment is needed to positively identify LI.
Published: 2018

22. Noncanonical hedgehog pathway activation through SRF–MKL1 promotes drug resistance in basal cell carcinomas

Author: Whitson, Ramon J, Lee, Alex, Urman, Nicole M, Mirza, Amar, Yao, Catherine Y, Brown, Alexander S, Li, Jiang R, Shankar, Gautam, Fry, Micah A, Atwood, Scott X, Lee, Eunice Y, Hollmig, S Tyler, Aasi, Sumaira Z, Sarin, Kavita Y, Scott, Matthew P, Epstein, Ervin H, Tang, Jean Y, and Oro, Anthony E
Subjects: Biomedical and Clinical Sciences, Health Sciences, Animals, Carcinoma, Basal Cell, Cell Line, Tumor, Cell Proliferation, Cell Survival, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Humans, Mice, Multiprotein Complexes, Serum Response Factor, Signal Transduction, Trans-Activators, Transcriptional Activation, Zinc Finger Protein GLI1, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract: Hedgehog pathway-dependent cancers can escape Smoothened (SMO) inhibition through mutations in genes encoding canonical hedgehog pathway components; however, around 50% of drug-resistant basal cell carcinomas (BCCs) lack additional variants of these genes. Here we use multidimensional genomics analysis of human and mouse drug-resistant BCCs to identify a noncanonical hedgehog activation pathway driven by the transcription factor serum response factor (SRF). Active SRF along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity. We show that cytoskeletal activation through Rho and the formin family member Diaphanous (mDia) is required for SRF-MKL-driven GLI1 activation and for tumor cell viability. Remarkably, nuclear MKL1 staining served as a biomarker in tumors from mice and human subjects to predict tumor responsiveness to MKL inhibitors, highlighting the therapeutic potential of targeting this pathway. Thus, our study illuminates, for the first time, cytoskeletal-activation-driven transcription as a personalized therapeutic target for combatting drug-resistant malignancies.
Published: 2018

23. Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers

Author: Popuri, Karteek, Dowds, Emma, Beg, Mirza Faisal, Balachandar, Rakesh, Bhalla, Mahadev, Jacova, Claudia, Buller, Adrienne, Slack, Penny, Sengdy, Pheth, Rademakers, Rosa, Wittenberg, Dana, Feldman, Howard H, Mackenzie, Ian R, and Hsiung, Ging-Yuek R
Subjects: Genetics, Clinical Research, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Rare Diseases, Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Frontotemporal Dementia (FTD), Acquired Cognitive Impairment, Biomedical Imaging, Aging, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Brain, C9orf72 Protein, Female, Frontotemporal Dementia, Gray Matter, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Organ Size, Progranulins, Frontotemporal dementia, Magnetic resonance imaging, C9orf72 mutation, Granulin mutation, Cortical thickness, Subcortical volumes
Abstract: Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72-) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN-) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subject's family. Mean age of C9orf72+ and C9orf72- were 42.6 ± 11.3 and 49.7 ± 15.5 years, respectively; while GRN+ and GRN- groups were 50.1 ± 8.7 and 53.2 ± 11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72- and GRN- combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease.
Published: 2018

24. Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children

Author: Jacobson, Denise L, Stephensen, Charles B, Miller, Tracie L, Patel, Kunjal, Chen, Janet S, Van Dyke, Russell B, Mirza, Ayesha, Schuster, Gertrud U, Hazra, Rohan, Ellis, Angela, Brummel, Sean S, Geffner, Mitchell E, Silio, Margarita, Spector, Stephen A, and DiMeglio, Linda A
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Clinical Research, Infectious Diseases, Osteoporosis, HIV/AIDS, Musculoskeletal, Good Health and Well Being, Adolescent, Bone Density, Bone Development, Child, Cohort Studies, Female, HIV Infections, Humans, Male, Parathyroid Hormone, Prevalence, Puberty, Randomized Controlled Trials as Topic, United States, Vitamin D, Vitamin D Deficiency, 25-hydroxy-vitamin D, parathyroid hormone, HIV infection, children, bone mineral density, Pediatric HIV/AIDS Cohort Study, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract: BackgroundPerinatally HIV-infected (PHIV) children have, on average, lower bone mineral density (BMD) than perinatally HIV-exposed uninfected (PHEU) and healthy children. Low 25-hydroxy vitamin D [25(OH)D] and elevated parathyroid hormone (PTH) concentrations may lead to suboptimal bone accrual.MethodsPHIV and PHEU children in the Pediatric HIV/AIDS Cohort Study had total body (TB) and lumbar spine (LS) BMD and bone mineral content (BMC) measured by dual-energy x-ray absorptiometry; BMD z-scores (BMDz) were calculated for age and sex. Low 25(OH)D was defined as ≤20 ng/mL and high PTH as >65 pg/mL. We fit linear regression models to estimate the average adjusted differences in BMD/BMC by 25(OH)D and PTH status and log binomial models to determine adjusted prevalence ratios of low 25(OH)D and high PTH in PHIV relative to PHEU children.ResultsPHIV children (n = 412) were older (13.0 vs. 10.8 years) and more often black (76% vs. 64%) than PHEU (n = 207). Among PHIV, children with low 25(OH)D had lower TB-BMDz [SD, -0.38; 95% confidence interval (CI), -0.60 to -0.16] and TB-BMC (SD, -59.1 g; 95% CI, -108.3 to -9.8); high PTH accompanied by low 25(OH)D was associated with lower TB-BMDz. Among PHEU, children with low 25(OH)D had lower TB-BMDz (SD, -0.34; 95% CI, -0.64 to -0.03). Prevalence of low 25(OH)D was similar by HIV status (adjusted prevalence ratio, 1.00; 95% CI, 0.81 to 1.24). High PTH was 3.17 (95% CI, 1.25 to 8.06) times more likely in PHIV children.ConclusionsPHIV and PHEU children with low 25(OH)D may have lower BMD. Vitamin D supplementation trials during critical periods of bone accrual are needed.
Published: 2017

25. A phase 3 trial of IV immunoglobulin for Alzheimer disease

Author: Relkin, Norman R, Thomas, Ronald G, Rissman, Robert A, Brewer, James B, Rafii, Michael S, van Dyck, Christopher H, Jack, Clifford R, Sano, Mary, Knopman, David S, Raman, Rema, Szabo, Paul, Gelmont, David M, Fritsch, Sandor, Aisen, Paul S, Ahern, Geoffrey, Yaari, Roy, Sabbagh, Marwan, Mirza, Nadeem, Bernick, Charles, Bell, Karen, Turner, R Scott, Obisesan, Thomas, Chertkow, Howard, Zabar, Yuval, Knopman, David, Mintzer, Jacobo, Grossman, Hillel, Sadowski, Martin, Wu, Chuang-Kuo, Quinn, Joseph, Borrie, Michael, Petrie, William, Ott, Brian, Keegan, Andrew, Grossberg, George, Bari, Moammed, Cohen, Sharon, Richter, Ralph, Lerner, Alan, Mulnard, Ruth, Potkin, Steven, Rafii, Michael, Brockington, John, Hsiung, Robin, Schultz, Susan, Burns, Jeffrey, Jicha, Gregory, Burke, William, Arnold, Steven, Porsteinsson, Anton, Smith, Amanda, Schneider, Lon, Quiceno, Mary, Zamrini, Edward, Asthana, Sanjay, Burgat, FT, Duara, Ranjan, and van Dyck, Christopher
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Clinical Trials and Supportive Activities, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Neurodegenerative, Clinical Research, Dementia, Acquired Cognitive Impairment, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Canada, Cognition, Double-Blind Method, Female, Humans, Immunoglobulins, Intravenous, Male, Middle Aged, Nootropic Agents, Peptide Fragments, Treatment Failure, United States, Alzheimer's Disease Cooperative Study, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveWe tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.MethodsIn a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.ResultsNo beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.ConclusionsParticipants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo.Clinicaltrialsgov identifierNCT00818662.Classification of evidenceThis study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.
Published: 2017

26. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: Adams, Hieab HH, Hibar, Derrek P, Chouraki, Vincent, Stein, Jason L, Nyquist, Paul A, Rentería, Miguel E, Trompet, Stella, Arias-Vasquez, Alejandro, Seshadri, Sudha, Desrivières, Sylvane, Beecham, Ashley H, Jahanshad, Neda, Wittfeld, Katharina, Van der Lee, Sven J, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beiser, Alexa, Bernard, Manon, Bis, Joshua C, Blanken, Laura ME, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chauhan, Ganesh, Chen, Qiang, Ching, Christopher RK, Cuellar-Partida, Gabriel, Braber, Anouk Den, Doan, Nhat Trung, Ehrlich, Stefan, Filippi, Irina, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Greven, Corina U, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Hass, Johanna, Haukvik, Unn K, Hilal, Saima, Hofer, Edith, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liao, Jiemin, Liewald, David CM, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, Mazoyer, Bernard, McKay, David R, McWhirter, Rebekah, Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Muetzel, Ryan L, Maniega, Susana Muñoz, Nho, Kwangsik, Nugent, Allison C, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pappa, Irene, Pirpamer, Lukas, Pudas, Sara, Pütz, Benno, Rajan, Kumar B, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, and Satizabal, Claudia L
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Human Genome, Biotechnology, Brain Disorders, Clinical Research, Aging, Prevention, Neurodegenerative, Genetics, 2.1 Biological and endogenous factors, Brain, Cognition, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Oncogene Protein v-akt, Parkinson Disease, Phenotype, Phosphatidylinositol 3-Kinases, Polymorphism, Single Nucleotide, White People, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016

27. Differences in Active and Passive Smoking Exposures and Lung Cancer Incidence Between Veterans and Non-Veterans in the Women’s Health Initiative

Author: Bastian, Lori A, Gray, Kristen E, DeRycke, Eric, Mirza, Shireen, Gierisch, Jennifer M, Haskell, Sally G, Magruder, Kathryn M, Wakelee, Heather A, Wang, Ange, Ho, Gloria YF, and LaCroix, Andrea Z
Subjects: Biomedical and Clinical Sciences, Epidemiology, Health Services and Systems, Public Health, Health Sciences, Lung, Prevention, Tobacco, Aging, Lung Cancer, Cancer, Tobacco Smoke and Health, Clinical Research, Aetiology, 2.2 Factors relating to the physical environment, Respiratory, Good Health and Well Being, Adenocarcinoma, Aged, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Female, Humans, Incidence, Lung Neoplasms, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors, Small Cell Lung Carcinoma, Smoking, Tobacco Smoke Pollution, United States, Veterans, Lung cancer, Women Veterans, Clinical Sciences, Gerontology
Abstract: IntroductionWomen Veterans may have higher rates of both active and passive tobacco exposure than their civilian counterparts, thereby increasing their risk for lung cancer.Purpose of the studyTo compare differences in active and passive smoking exposure and lung cancer incidence among women Veterans and non-Veterans using prospective data from the Women's Health Initiative (WHI).Design and methodsWe used data from the WHI, which collected longitudinal demographic, clinical, and laboratory data on 161,808 postmenopausal women. We employed linear and multinomial regression and generalized linear models to compare active and passive smoking exposure between Veterans and non-Veterans and Cox proportional hazards models to estimate differences in lung cancer incidence rates.ResultsAfter adjustment, Veterans had 2.54 additional pack years of smoking compared with non-Veterans (95% confidence interval [CI] 1.68, 3.40). Veterans also had a 1% increase in risk of any passive smoking exposure (95% CI 1.00, 1.02) and a 9% increase in risk of any workplace exposure (95% CI 1.07, 1.11) compared with non-Veterans. After adjustment for age and smoking exposures, Veterans did not have a higher risk of lung cancer compared with non-Veterans (relative risk = 1.06 95% CI 0.86, 1.30).ImplicationsWomen Veterans had higher rates of tobacco use and exposure to passive smoking, which were associated with a higher risk for lung cancer compared with non-Veterans. Clinicians who care for Veterans need to be aware that older women Veterans have more exposures to risk factors for lung cancer.
Published: 2016

28. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author: Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, deJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA, Palotie, A, Hsieh, Y-C, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, and Chasman, DI
Subjects: Biological Psychology, Clinical and Health Psychology, Psychology, Human Genome, Neurosciences, Genetics, Clinical Research, Aging, Aetiology, 2.1 Biological and endogenous factors, Aged, Aged, 80 and over, Cell Adhesion Molecules, Cognition, Cohort Studies, Executive Function, Female, Genetic Association Studies, Genetic Variation, Genome-Wide Association Study, Genomics, Humans, Introns, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Single Nucleotide, White People, gamma-Aminobutyric Acid, Generation Scotland, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
Published: 2016

29. Tumor-Derived Suppressor of Fused Mutations Reveal Hedgehog Pathway Interactions.

Author: Urman, Nicole M, Mirza, Amar, Atwood, Scott X, Whitson, Ramon J, Sarin, Kavita Y, Tang, Jean Y, and Oro, Anthony E
Subjects: NIH 3T3 Cells, Animals, Humans, Mice, Carcinoma, Basal Cell, Skin Neoplasms, Disease Progression, Repressor Proteins, Signal Transduction, Cell Proliferation, Protein Conformation, Mutation, Models, Molecular, Hedgehog Proteins, Young Adult, HEK293 Cells, Carcinogenesis, Zinc Finger Protein GLI1, General Science & Technology
Abstract: The Hedgehog pathway is a potent regulator of cellular growth and plays a central role in the development of many cancers including basal cell carcinoma (BCC). The majority of BCCs arise from mutations in the Patched receptor resulting in constitutive activation of the Hedgehog pathway. Secondary driver mutations promote BCC oncogenesis and occur frequently due to the high mutational burden resulting from sun exposure of the skin. Here, we uncover novel secondary mutations in Suppressor of Fused (SUFU), the major negative regulator of the Hedgehog pathway. SUFU normally binds to a Hedgehog transcriptional activator, GLI1, in order to prevent it from initiating transcription of Hedgehog target genes. We sequenced tumor-normal pairs from patients with early sporadic BCCs. This resulted in the discovery of nine mutations in SUFU, which were functionally investigated to determine whether they help drive BCC formation. Our results show that four of the SUFU mutations inappropriately activate the Hedgehog pathway, suggesting they may act as driver mutations for BCC development. Indeed, all four of the loss of function SUFU variants were found to disrupt its binding to GLI, leading to constitutive pathway activation. Our results from functional characterization of these mutations shed light on SUFU's role in Hedgehog signaling, tumor progression, and highlight a way in which BCCs can arise.
Published: 2016

30. Dual domestications and origin of traits in grapevine evolution

Author: Yang Dong, Shengchang Duan, Qiuju Xia, Zhenchang Liang, Xiao Dong, Kristine Margaryan, Mirza Musayev, Svitlana Goryslavets, Goran Zdunić, Pierre-François Bert, Thierry Lacombe, Erika Maul, Peter Nick, Kakha Bitskinashvili, György Dénes Bisztray, Elyashiv Drori, Gabriella De Lorenzis, Jorge Cunha, Carmen Florentina Popescu, Rosa Arroyo-Garcia, Claire Arnold, Ali Ergül, Yifan Zhu, Chao Ma, Shufen Wang, Siqi Liu, Liu Tang, Chunping Wang, Dawei Li, Yunbing Pan, Jingxian Li, Ling Yang, Xuzhen Li, Guisheng Xiang, Zijiang Yang, Baozheng Chen, Zhanwu Dai, Yi Wang, Arsen Arakelyan, Varis Kuliyev, Gennady Spotar, Nabil Girollet, Serge Delrot, Nathalie Ollat, Patrice This, Cécile Marchal, Gautier Sarah, Valérie Laucou, Roberto Bacilieri, Franco Röckel, Pingyin Guan, Andreas Jung, Michael Riemann, Levan Ujmajuridze, Tekle Zakalashvili, David Maghradze, Maria Höhn, Gizella Jahnke, Erzsébet Kiss, Tamás Deák, Oshrit Rahimi, Sariel Hübner, Fabrizio Grassi, Francesco Mercati, Francesco Sunseri, José Eiras-Dias, Anamaria Mirabela Dumitru, David Carrasco, Alberto Rodriguez-Izquierdo, Gregorio Muñoz, Tamer Uysal, Cengiz Özer, Kemal Kazan, Meilong Xu, Yunyue Wang, Shusheng Zhu, Jiang Lu, Maoxiang Zhao, Lei Wang, Songtao Jiu, Ying Zhang, Lei Sun, Huanming Yang, Ehud Weiss, Shiping Wang, Youyong Zhu, Shaohua Li, Jun Sheng, Wei Chen, Duan, Shengchang, Xia, Qiuju, Liang, Zhenchang, Margaryan, Kristine, Musayev, Mirza, Goryslavets, Svitlana, Zdunić, Goran, Bert, Pierre-François, Lacombe, Thierry, Maul, Erika, Bitskinashvili, Kakha, Bisztray, György Dénes, Drori, Elyashiv, De Lorenzis, Gabriella, Popescu, Carmen Florentina, Arroyo García, Rosa Adela, Chen, Baozheng, Dai, Zhanwu, Spotar, Gennady, Girollet, Nabil, Delrot, Serge, Ollat, Nathalie, This, Patrice, Sarah, Gautier, Laucou, Valérie, Bacilieri, Roberto, Röckel, Franco, Guan, Pingyin, Riemann, Michael, Ujmajuridze, Levan, Zakalashvili, Tekle, Höhn, Maria, Jahnke, Gizella, Kiss, Erzsébet, Deák, Tamás, Rahimi, Oshrit, Hübner, Sariel, Grassi, Fabrizio, Mercati, Francesco, Eiras-Dias, José, Dumitru, Anamaria Mirabela, Carrasco, David, Rodriguez-Izquierdo, Alberto, Muñoz, Gregorio, Uysal, Tamer, Özer, Cengiz, Kazan, Kemal, Wang, Yunyue, Zhao, Maoxiang, Weiss, Ehud, Dong, Y, Duan, S, Xia, Q, Liang, Z, Dong, X, Margaryan, K, Musayev, M, Goryslavets, S, Zdunić, G, Bert, P, Lacombe, T, Maul, E, Nick, P, Bitskinashvili, K, Bisztray, G, Drori, E, De Lorenzis, G, Cunha, J, Popescu, C, Arroyo-Garcia, R, Arnold, C, Ergül, A, Zhu, Y, Ma, C, Wang, S, Liu, S, Tang, L, Wang, C, Li, D, Pan, Y, Li, J, Yang, L, Li, X, Xiang, G, Yang, Z, Chen, B, Dai, Z, Wang, Y, Arakelyan, A, Kuliyev, V, Spotar, G, Girollet, N, Delrot, S, Ollat, N, This, P, Marchal, C, Sarah, G, Laucou, V, Bacilieri, R, Röckel, F, Guan, P, Jung, A, Riemann, M, Ujmajuridze, L, Zakalashvili, T, Maghradze, D, Höhn, M, Jahnke, G, Kiss, E, Deák, T, Rahimi, O, Hübner, S, Grassi, F, Mercati, F, Sunseri, F, Eiras-Dias, J, Dumitru, A, Carrasco, D, Rodriguez-Izquierdo, A, Muñoz, G, Uysal, T, Özer, C, Kazan, K, Xu, M, Zhu, S, Lu, J, Zhao, M, Wang, L, Jiu, S, Zhang, Y, Sun, L, Yang, H, Weiss, E, Li, S, Sheng, J, and Chen, W
Subjects: Domestication, Ecotype, Phenotype, Multidisciplinary, Acclimatization, Grapes, domestication, origin, Genetics, Humans, genetic diversity, genomic history, accessions, holocene, insights, Agriculture, Vitis, Asia Western, Biological Evolution
Abstract: We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.
Published: 2023
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31. Gleason 6 Prostate Cancer: Translating Biology into Population Health

Author: Eggener, Scott E, Badani, Ketan, Barocas, Daniel A, Barrisford, Glen W, Cheng, Jed-Sian, Chin, Arnold I, Corcoran, Anthony, Epstein, Jonathan I, George, Arvin K, Gupta, Gopal N, Hayn, Matthew H, Kauffman, Eric C, Lane, Brian, Liss, Michael A, Mirza, Moben, Morgan, Todd M, Moses, Kelvin, Nepple, Kenneth G, Preston, Mark A, Rais-Bahrami, Soroush, Resnick, Matthew J, Siddiqui, M Minhaj, Silberstein, Jonathan, Singer, Eric A, Sonn, Geoffrey A, Sprenkle, Preston, Stratton, Kelly L, Taylor, Jennifer, Tomaszewski, Jeffrey, Tollefson, Matt, Vickers, Andrew, White, Wesley M, and Lowrance, William T
Subjects: Clinical Research, Prostate Cancer, Urologic Diseases, Prevention, Health Services, Aging, Cancer, Detection, screening and diagnosis, 4.4 Population screening, Good Health and Well Being, Early Detection of Cancer, Humans, Male, Neoplasm Grading, Prognosis, Prostatic Neoplasms, Risk Assessment, Watchful Waiting, prostatic neoplasms, neoplasm grading, early detection of cancer, watchful waiting, prostatectomy
Abstract: PurposeGleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management.Materials and methodsMembers of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes.ResultsThe Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes.ConclusionsThe definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.
Published: 2015

32. Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor

Author: Kovacs, Erika, Das, Rahul, Wang, Qi, Collier, Timothy S, Cantor, Aaron, Huang, Yongjian, Wong, Kathryn, Mirza, Amar, Barros, Tiago, Grob, Patricia, Jura, Natalia, Bose, Ron, and Kuriyan, John
Subjects: Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Amino Acid Sequence, Animals, COS Cells, Cell Line, Chlorocebus aethiops, Crystallography, X-Ray, Enzyme Activation, ErbB Receptors, Flow Cytometry, HEK293 Cells, Humans, Molecular Dynamics Simulation, Phosphorylation, Protein Structure, Tertiary, Sequence Deletion, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: The ∼230-residue C-terminal tail of the epidermal growth factor receptor (EGFR) is phosphorylated upon activation. We examined whether this phosphorylation is affected by deletions within the tail and whether the two tails in the asymmetric active EGFR dimer are phosphorylated differently. We monitored autophosphorylation in cells using flow cytometry and found that the first ∼80 residues of the tail are inhibitory, as demonstrated previously. The entire ∼80-residue span is important for autoinhibition and needs to be released from both kinases that form the dimer. These results are interpreted in terms of crystal structures of the inactive kinase domain, including two new ones presented here. Deletions in the remaining portion of the tail do not affect autophosphorylation, except for a six-residue segment spanning Tyr 1086 that is critical for activation loop phosphorylation. Phosphorylation of the two tails in the dimer is asymmetric, with the activator tail being phosphorylated somewhat more strongly. Unexpectedly, we found that reconstitution of the transmembrane and cytoplasmic domains of EGFR in vesicles leads to a peculiar phenomenon in which kinase domains appear to be trapped between stacks of lipid bilayers. This artifactual trapping of kinases between membranes enhances an intrinsic functional asymmetry in the two tails in a dimer.
Published: 2015

33. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U, Schurmann, Claudia, Smith, Albert V, Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D, Zhao, Wei, Bartz, Traci M, Concas, Maria Pina, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I, O'Connel, Jeffrey R, Corre, Tanguy, Nongmaithem, Suraj S, Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki-Eleni, Kacprowski, Tim, Bjonnes, Andrew, van der Spek, Ashley, Wu, Ying, Giri, Anil K, Yanek, Lisa R, Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A, McLeod, Olga, Cornelis, Marilyn C, Pattaro, Cristian, Verweij, Niek, Baumbach, Clemens, Abdellaoui, Abdel, Warren, Helen R, Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John RB, Cappellani, Stefania, Mirza, Saira S, Benton, Miles C, Broeckel, Ulrich, Medland, Sarah E, Lind, Penelope A, Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F, Zhi, Degui, van der Most, Peter J, Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaros, van der Laan, Sander W, Bradfield, Jonathan P, Wood, Andrew R, Bonnefond, Amelie, Ahluwalia, Tarunveer S, Hall, Leanne M, Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, de Haan, Hugoline G, Abney, Mark, Afzal, Uzma, Allison, Matthew A, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan JL, Barr, R Graham, Baumeister, Sebastian E, Benjamin, Daniel J, Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P, Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J, Chen, Constance, and Chen, Y-D Ida
Subjects: Biological Sciences, Genetics, Clinical Research, Human Genome, Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype, General Science & Technology
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
Published: 2015

34. Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers

Author: Watkins, Johnathan, Weekes, Daniel, Shah, Vandna, Gazinska, Patrycja, Joshi, Shalaka, Sidhu, Bhavna, Gillett, Cheryl, Pinder, Sarah, Vanoli, Fabio, Jasin, Maria, Mayrhofer, Markus, Isaksson, Anders, Cheang, Maggie CU, Mirza, Hasan, Frankum, Jessica, Lord, Christopher J, Ashworth, Alan, Vinayak, Shaveta, Ford, James M, Telli, Melinda L, Grigoriadis, Anita, and Tutt, Andrew NJ
Subjects: Human Genome, Cancer, Biotechnology, Genetics, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Allelic Imbalance, Antineoplastic Combined Chemotherapy Protocols, Cell Cycle Proteins, Cell Line, Tumor, Cell Nucleus, Cell Survival, Chromosomal Instability, Cluster Analysis, DNA Copy Number Variations, Drug Resistance, Neoplasm, Gene Expression, Gene Expression Profiling, Gene Silencing, Genomics, Homologous Recombination, Humans, Platinum, Polymorphism, Single Nucleotide, RNA, Small Interfering, Triple Negative Breast Neoplasms, Oncology and Carcinogenesis
Abstract: UnlabelledTriple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination (HR). Despite this understanding, associating particular patterns of genomic instability with response to therapy has been challenging. Here, we show that allelic-imbalanced copy-number aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based chemotherapy, thus providing a candidate predictive biomarker for this disease. Furthermore, we show that a high level of AiCNA is linked with elevated expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression suppresses RAD51-dependent HR and drives the use of alternative forms of DNA repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR-targeting therapies. Our data therefore provide a mechanistic association between HORMAD1 expression, a specific pattern of genomic instability, and an association with response to platinum-based chemotherapy in TNBC.SignificancePrevious studies have shown correlation between mutational "scars" and sensitivity to platinums extending beyond associations with BRCA1/2 mutation, but do not elucidate the mechanism. Here, a novel allele-specific copy-number characterization of genome instability identifies and functionally validates the inappropriate expression of the meiotic gene HORMAD1 as a driver of HR deficiency in TNBC, acting to induce allelic imbalance and moderate platinum and PARP inhibitor sensitivity with implications for the use of such "scars" and expression of meiotic genes as predictive biomarkers.
Published: 2015

35. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

Author: Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, van der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Generation Scotland, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N, Knopman, DS, Kwok, JB, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, van Swieten, JC, Taylor, KD, Trollor, J, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, and Wright, AF
Subjects: Generation Scotland, Humans, Genetic Predisposition to Disease, HMGN1 Protein, Cohort Studies, Cognition, Cognition Disorders, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Scotland, Female, Male, Atherosclerosis, Genome-Wide Association Study, and over, Polymorphism, Single Nucleotide, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract: General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
Published: 2015

36. Thickness network features for prognostic applications in dementia

Author: Raamana, Pradeep Reddy, Weiner, Michael W, Wang, Lei, Beg, Mirza Faisal, and Initiative, Alzheimer's Disease Neuroimaging
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Aging, Prevention, Neurodegenerative, Acquired Cognitive Impairment, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Brain Disorders, Biomedical Imaging, Neurological, Alzheimer Disease, Biomarkers, Cerebral Cortex, Cognitive Dysfunction, Diagnosis, Differential, Early Diagnosis, Humans, Magnetic Resonance Imaging, Neuroimaging, Prognosis, Sensitivity and Specificity, Cortical thickness, Network properties, Fusion, Multiple kernel learning, Early detection, Mild cognitive impairment, Alzheimer, Alzheimer's Disease Neuroimaging Initiative, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Regional analysis of cortical thickness has been studied extensively in building imaging biomarkers for early detection of Alzheimer's disease but not its interregional covariation of thickness. We present novel features based on the inter-regional covariation of cortical thickness. Initially, the cortical labels of each subject are partitioned into small patches (graph nodes) by spatial k-means clustering. A graph is then constructed by establishing a link between 2 nodes if the difference in thickness between the nodes is below a certain threshold. From this binary graph, a thickness network is computed using nodal degree, betweenness, and clustering coefficient measures. Fusing them with multiple kernel learning, it is observed that thickness network features discriminate mild cognitive impairment (MCI) converters from controls (CN) with an area under curve (AUC) of 0.83, 74% sensitivity and 76% specificity on a large subset obtained from the Alzheimer's Disease Neuroimaging Initiative data set. A comparison of predictive utility in Alzheimer's disease and/or CN classification (AUC of 0.92, 80% sensitivity [SENS] and 90% specificity [SPEC]), in discriminating CN from MCI (converters and nonconverters combined; AUC of 0.75, SENS and SPEC of 64% and 73%, respectively) and in discriminating between MCI nonconverters and MCI converters (AUC of 0.68, SENS and SPEC of 65% and 64%) is also presented. ThickNet features as defined here are novel, can be derived from a single magnetic resonance imaging scan, and demonstrate the potential for the computer-aided prognostic applications.
Published: 2015

37. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Rajesh Sharma, Mohsen Abbasi-Kangevari, Rami Abd-Rabu, Hassan Abidi, Eman Abu-Gharbieh, Juan Manuel Acuna, Sangeet Adhikari, Shailesh M Advani, Muhammad Sohail Afzal, Mohamad Aghaie Meybodi, Bright Opoku Ahinkorah, Sajjad Ahmad, Ali Ahmadi, Sepideh Ahmadi, Haroon Ahmed, Luai A Ahmed, Muktar Beshir Ahmed, Hanadi Al Hamad, Fares Alahdab, Fahad Mashhour Alanezi, Turki M Alanzi, Fadwa Alhalaiqa Naji Alhalaiqa, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Sami Almustanyir, Rajaa M Al-Raddadi, Saba Alvand, Nelson Alvis-Guzman, Saeed Amini, Robert Ancuceanu, Amir Anoushiravani, Ali Arash Anoushirvani, Alireza Ansari-Moghaddam, Jalal Arabloo, Armin Aryannejad, Mohammad Asghari Jafarabadi, Seyyed Shamsadin Athari, Floriane Ausloos, Marcel Ausloos, Atalel Fentahun Awedew, Mamaru Ayenew Awoke, Tegegn Mulatu Ayana, Sina Azadnajafabad, Hiva Azami, Mohammadreza Azangou-Khyavy, Amirhossein Azari Jafari, Ashish D Badiye, Sara Bagherieh, Saeed Bahadory, Atif Amin Baig, Jennifer L Baker, Maciej Banach, Amadou Barrow, Alemshet Yirga Berhie, Sima Besharat, Devidas S Bhagat, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Sadia Bibi, Ali Bijani, Antonio Biondi, Tone Bjørge, Belay Boda Abule Bodicha, Dejana Braithwaite, Hermann Brenner, Daniela Calina, Chao Cao, Yin Cao, Giulia Carreras, Felix Carvalho, Ester Cerin, Raja Chandra Chakinala, William C S Cho, Dinh-Toi Chu, Joao Conde, Vera Marisa Costa, Natália Cruz-Martins, Omid Dadras, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Anna Danielewicz, Feleke Mekonnen Demeke, Getu Debalkie Demissie, Rupak Desai, Deepak Dhamnetiya, Mostafa Dianatinasab, Daniel Diaz, Mojtaba Didehdar, Saeid Doaei, Linh Phuong Doan, Milad Dodangeh, Fatemeh Eghbalian, Debela Debela Ejeta, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Iman El Sayed, Muhammed Elhadi, Daniel Berhanie Enyew, Tahir Eyayu, Rana Ezzeddini, Ildar Ravisovich Fakhradiyev, Umar Farooque, Hossein Farrokhpour, Farshad Farzadfar, Ali Fatehizadeh, Hamed Fattahi, Nima Fattahi, Masood Fereidoonnezhad, Eduarda Fernandes, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Mohamed M Gad, Silvano Gallus, Tushar Garg, Tamiru Getachew, Seyyed-Hadi Ghamari, Ahmad Ghashghaee, Nermin Ghith, Maryam Gholamalizadeh, Jamshid Gholizadeh Navashenaq, Abraham Tamirat Gizaw, James C Glasbey, Mahaveer Golechha, Pouya Goleij, Kebebe Bekele Gonfa, Giuseppe Gorini, Avirup Guha, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Rasool Haddadi, Nima Hafezi-Nejad, Arvin Haj-Mirzaian, Rabih Halwani, Shafiul Haque, Sanam Hariri, Ahmed I Hasaballah, Soheil Hassanipour, Simon I Hay, Claudiu Herteliu, Ramesh Holla, Mohammad-Salar Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Mowafa Househ, Junjie Huang, Ayesha Humayun, Ivo Iavicoli, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Farhad Islami, Masao Iwagami, Mohammad Ali Jahani, Mihajlo Jakovljevic, Tahereh Javaheri, Ranil Jayawardena, Rime Jebai, Ravi Prakash Jha, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Jacek Jerzy Jozwiak, Ali Kabir, Rohollah Kalhor, Ashwin Kamath, Neeti Kapoor, Ibraheem M Karaye, Amirali Karimi, Joonas H Kauppila, Asma Kazemi, Mohammad Keykhaei, Yousef Saleh Khader, Himanshu Khajuria, Rovshan Khalilov, Javad Khanali, Maryam Khayamzadeh, Mahmoud Khodadost, Hanna Kim, Min Seo Kim, Adnan Kisa, Sezer Kisa, Ali-Asghar Kolahi, Hamid Reza Koohestani, Jacek A Kopec, Rajasekaran Koteeswaran, Ai Koyanagi, Yuvaraj Krishnamoorthy, G Anil Kumar, Manoj Kumar, Vivek Kumar, Carlo La Vecchia, Faris Hasan Lami, Iván Landires, Caterina Ledda, Sang-woong Lee, Wei-Chen Lee, Yeong Yeh Lee, Elvynna Leong, Bingyu Li, Stephen S Lim, Stany W Lobo, Joana A Loureiro, Raimundas Lunevicius, Farzan Madadizadeh, Ata Mahmoodpoor, Azeem Majeed, Mohammad-Reza Malekpour, Reza Malekzadeh, Ahmad Azam Malik, Fariborz Mansour-Ghanaei, Lorenzo Giovanni Mantovani, Miquel Martorell, Sahar Masoudi, Prashant Mathur, Jitendra Kumar Meena, Entezar Mehrabi Nasab, Walter Mendoza, Alexios-Fotios A Mentis, Tomislav Mestrovic, Junmei Miao Jonasson, Bartosz Miazgowski, Tomasz Miazgowski, Gelana Fekadu Worku Mijena, Seyyedmohammadsadeq Mirmoeeni, Mohammad Mirza-Aghazadeh-Attari, Hamed Mirzaei, Sanjeev Misra, Karzan Abdulmuhsin Mohammad, Esmaeil Mohammadi, Saeed Mohammadi, Seyyede Momeneh Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Teroj Abdulrahman Mohammed, Nagabhishek Moka, Ali H Mokdad, Zeinab Mokhtari, Mariam Molokhia, Sara Momtazmanesh, Lorenzo Monasta, Ghobad Moradi, Rahmatollah Moradzadeh, Paula Moraga, Joana Morgado-da-Costa, Sumaira Mubarik, Francesk Mulita, Mohsen Naghavi, Mukhammad David Naimzada, Hae Sung Nam, Zuhair S Natto, Biswa Prakash Nayak, Javad Nazari, Ehsan Nazemalhosseini-Mojarad, Ionut Negoi, Cuong Tat Nguyen, Son Hoang Nguyen, Nurulamin M Noor, Maryam Noori, Seyyed Mohammad Ali Noori, Virginia Nuñez-Samudio, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Oluwakemi Ololade Odukoya, Ayodipupo Sikiru Oguntade, Hassan Okati-Aliabad, Andrew T Olagunju, Tinuke O Olagunju, Sokking Ong, Samuel M Ostroff, Alicia Padron-Monedero, Reza Pakzad, Adrian Pana, Anamika Pandey, Fatemeh Pashazadeh Kan, Urvish K Patel, Uttam Paudel, Renato B Pereira, Navaraj Perumalsamy, Richard G Pestell, Zahra Zahid Piracha, Richard Charles G Pollok, Akram Pourshams, Naeimeh Pourtaheri, Akila Prashant, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Sima Rafiei, Mosiur Rahman, Amir Masoud Rahmani, Vahid Rahmanian, Nazanin Rajai, Aashish Rajesh, Vajiheh Ramezani-Doroh, Kiana Ramezanzadeh, Kamal Ranabhat, Sina Rashedi, Amirfarzan Rashidi, Mahsa Rashidi, Mohammad-Mahdi Rashidi, Mandana Rastegar, David Laith Rawaf, Salman Rawaf, Reza Rawassizadeh, Mohammad Sadegh Razeghinia, Andre M N Renzaho, Negar Rezaei, Nima Rezaei, Saeid Rezaei, Mohsen Rezaeian, Sahba Rezazadeh-Khadem, Gholamreza Roshandel, Maha Mohamed Saber-Ayad, Bahar Saberzadeh-Ardestani, Basema Saddik, Hossein Sadeghi, Umar Saeed, Maryam Sahebazzamani, Amirhossein Sahebkar, Amir Salek Farrokhi, Amir Salimi, Hamideh Salimzadeh, Pouria Samadi, Mehrnoosh Samaei, Abdallah M Samy, Juan Sanabria, Milena M Santric-Milicevic, Muhammad Arif Nadeem Saqib, Arash Sarveazad, Brijesh Sathian, Maheswar Satpathy, Ione Jayce Ceola Schneider, Mario Šekerija, Sadaf G Sepanlou, Allen Seylani, Feng Sha, Sayed Mohammad Shafiee, Zahra Shaghaghi, Saeed Shahabi, Elaheh Shaker, Maedeh Sharifian, Javad Sharifi-Rad, Sara Sheikhbahaei, Jeevan K Shetty, Reza Shirkoohi, Parnian Shobeiri, Sudeep K Siddappa Malleshappa, Diego Augusto Santos Silva, Guilherme Silva Julian, Achintya Dinesh Singh, Jasvinder A Singh, Md Shahjahan Siraj, Gholam Reza Sivandzadeh, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Bogdan Socea, Marco Solmi, Mohammad Sadegh Soltani-Zangbar, Suhang Song, Viktória Szerencsés, Miklós Szócska, Rafael Tabarés-Seisdedos, Elnaz Tabibian, Majid Taheri, Yasaman TaheriAbkenar, Amir Taherkhani, Iman M Talaat, Ker-Kan Tan, Abdelghani Tbakhi, Bekele Tesfaye, Amir Tiyuri, Daniel Nigusse Tollosa, Mathilde Touvier, Bach Xuan Tran, Biruk Shalmeno Tusa, Irfan Ullah, Saif Ullah, Marco Vacante, Sahel Valadan Tahbaz, Massimiliano Veroux, Bay Vo, Theo Vos, Cong Wang, Ronny Westerman, Melat Woldemariam, Seyed Hossein Yahyazadeh Jabbari, Lin Yang, Fereshteh Yazdanpanah, Chuanhua Yu, Deniz Yuce, Ismaeel Yunusa, Vesna Zadnik, Mazyar Zahir, Iman Zare, Zhi-Jiang Zhang, Mohammad Zoladl, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Sharma, Rajesh, Abbasi-Kangevari, Mohsen, Abd-Rabu, Rami, Abidi, Hassan, Ahmed, Muktar Beshir, Zoladl, Mohammad, GBD 2019 Colorectal Cancer Collaborators, Sharma, R, Abbasi-Kangevari, M, Abd-Rabu, R, Abidi, H, Abu-Gharbieh, E, Manuel Acuna, J, Adhikari, S, M Advani, S, Sohail Afzal, M, Aghaie Meybodi, M, Opoku Ahinkorah, B, Ahmad, S, Ahmadi, A, Ahmadi, S, Ahmed, H, A Ahmed, L, Beshir Ahmed, M, Al Hamad, H, Alahdab, F, Mashhour Alanezi, F, M Alanzi, T, Alhalaiqa Naji Alhalaiqa, F, Alimohamadi, Y, Alipour, V, Mohamed Aljunid, S, Alkhayyat, M, Almustanyir, S, M Al-Raddadi, R, Alvand, S, Alvis-Guzman, N, Amini, S, Ancuceanu, R, Anoushiravani, A, Arash Anoushirvani, A, Ansari-Moghaddam, A, Arabloo, J, Aryannejad, A, Asghari Jafarabadi, M, Shamsadin Athari, S, Ausloos, F, Ausloos, M, Fentahun Awedew, A, Ayenew Awoke, M, Mulatu Ayana, T, Azadnajafabad, S, Azami, H, Azangou-Khyavy, M, Azari Jafari, A, D Badiye, A, Bagherieh, S, Bahadory, S, Amin Baig, A, L Baker, J, Banach, M, Barrow, A, Yirga Berhie, A, Besharat, S, S Bhagat, D, Srikanth Bhagavathula, A, Bhala, N, Bhattacharyya, K, S Bhojaraja, V, Bibi, S, Bijani, A, Biondi, A, Bj??rge, T, Boda Abule Bodicha, B, Braithwaite, D, Brenner, H, Calina, D, Cao, C, Cao, Y, Carreras, G, Carvalho, F, Cerin, E, Chandra Chakinala, R, S Cho, W, Chu, D, Conde, J, Marisa Costa, V, Cruz-Martins, N, Dadras, O, Dai, X, Dandona, L, Dandona, R, Danielewicz, A, Mekonnen Demeke, F, Debalkie Demissie, G, Desai, R, Dhamnetiya, D, Dianatinasab, M, Diaz, D, Didehdar, M, Doaei, S, Phuong Doan, L, Dodangeh, M, Eghbalian, F, Debela Ejeta, D, Ekholuenetale, M, Cyrus Ekundayo, T, El Sayed, I, Elhadi, M, Berhanie Enyew, D, Eyayu, T, Ezzeddini, R, Ravisovich Fakhradiyev, I, Farooque, U, Farrokhpour, H, Farzadfar, F, Fatehizadeh, A, Fattahi, H, Fattahi, N, Fereidoonnezhad, M, Fernandes, E, Fetensa, G, Filip, I, Fischer, F, Foroutan, M, Andras Gaal, P, M Gad, M, Gallus, S, Garg, T, Getachew, T, Ghamari, S, Ghashghaee, A, Ghith, N, Gholamalizadeh, M, Gholizadeh Navashenaq, J, Tamirat Gizaw, A, C Glasbey, J, Golechha, M, Goleij, P, Bekele Gonfa, K, Gorini, G, Guha, A, Gupta, S, Bala Gupta, V, Kumar Gupta, V, Haddadi, R, Hafezi-Nejad, N, Haj-Mirzaian, A, Halwani, R, Haque, S, Hariri, S, I Hasaballah, A, Hassanipour, S, I Hay, S, Herteliu, C, Holla, R, Hosseini, M, Hosseinzadeh, M, Hostiuc, M, Househ, M, Huang, J, Humayun, A, Iavicoli, I, Stephen Ilesanmi, O, M Ilic, I, D Ilic, M, Islami, F, Iwagami, M, Ali Jahani, M, Jakovljevic, M, Javaheri, T, Jayawardena, R, Jebai, R, Prakash Jha, R, Joo, T, Joseph, N, Joukar, F, Jerzy Jozwiak, J, Kabir, A, Kalhor, R, Kamath, A, Kapoor, N, M Karaye, I, Karimi, A, H Kauppila, J, Kazemi, A, Keykhaei, M, Saleh Khader, Y, Khajuria, H, Khalilov, R, Khanali, J, Khayamzadeh, M, Khodadost, M, Kim, H, Seo Kim, M, Kisa, A, Kisa, S, Kolahi, A, Reza Koohestani, H, A Kopec, J, Koteeswaran, R, Koyanagi, A, Krishnamoorthy, Y, Anil Kumar, G, Kumar, M, Kumar, V, La Vecchia, C, Hasan Lami, F, Landires, I, Ledda, C, Lee, S, Lee, W, Yeh Lee, Y, Leong, E, Li, B, S Lim, S, W Lobo, S, A Loureiro, J, Lunevicius, R, Madadizadeh, F, Mahmoodpoor, A, Majeed, A, Malekpour, M, Malekzadeh, R, Azam Malik, A, Mansour-Ghanaei, F, Mantovani, L, Martorell, M, Masoudi, S, Mathur, P, Kumar Meena, J, Mehrabi Nasab, E, Mendoza, W, A Mentis, A, Mestrovic, T, Miao Jonasson, J, Miazgowski, B, Miazgowski, T, Fekadu Worku Mijena, G, Mirmoeeni, S, Mirza-Aghazadeh-Attari, M, Mirzaei, H, Misra, S, Abdulmuhsin Mohammad, K, Mohammadi, E, Mohammadi, S, Momeneh Mohammadi, S, Mohammadian-Hafshejani, A, Mohammed, S, Abdulrahman Mohammed, T, Moka, N, H Mokdad, A, Mokhtari, Z, Molokhia, M, Momtazmanesh, S, Monasta, L, Moradi, G, Moradzadeh, R, Moraga, P, Morgado-da-Costa, J, Mubarik, S, Mulita, F, Naghavi, M, David Naimzada, M, Sung Nam, H, S Natto, Z, Prakash Nayak, B, Nazari, J, Nazemalhosseini-Mojarad, E, Negoi, I, Tat Nguyen, C, Hoang Nguyen, S, M Noor, N, Noori, M, Mohammad Ali Noori, S, Nu??ez-Samudio, V, Igwegbe Nzoputam, C, Oancea, B, Ololade Odukoya, O, Sikiru Oguntade, A, Okati-Aliabad, H, T Olagunju, A, O Olagunju, T, Ong, S, M Ostroff, S, Padron-Monedero, A, Pakzad, R, Pana, A, Pandey, A, Pashazadeh Kan, F, K Patel, U, Paudel, U, B Pereira, R, Perumalsamy, N, G Pestell, R, Zahid Piracha, Z, G Pollok, R, Pourshams, A, Pourtaheri, N, Prashant, A, Rabiee, M, Rabiee, N, Radfar, A, Rafiei, S, Rahman, M, Masoud Rahmani, A, Rahmanian, V, Rajai, N, Rajesh, A, Ramezani-Doroh, V, Ramezanzadeh, K, Ranabhat, K, Rashedi, S, Rashidi, A, Rashidi, M, Rastegar, M, Laith Rawaf, D, Rawaf, S, Rawassizadeh, R, Sadegh Razeghinia, M, N Renzaho, A, Rezaei, N, Rezaei, S, Rezaeian, M, Rezazadeh-Khadem, S, Roshandel, G, Mohamed Saber-Ayad, M, Saberzadeh-Ardestani, B, Saddik, B, Sadeghi, H, Saeed, U, Sahebazzamani, M, Sahebkar, A, Salek Farrokhi, A, Salimi, A, Salimzadeh, H, Samadi, P, Samaei, M, M Samy, A, Sanabria, J, M Santric-Milicevic, M, Arif Nadeem Saqib, M, Sarveazad, A, Sathian, B, Satpathy, M, Jayce Ceola Schneider, I, ekerija, M, G Sepanlou, S, Seylani, A, Sha, F, Mohammad Shafiee, S, Shaghaghi, Z, Shahabi, S, Shaker, E, Sharifian, M, Sharifi-Rad, J, Sheikhbahaei, S, K Shetty, J, Shirkoohi, R, Shobeiri, P, K Siddappa Malleshappa, S, Augusto Santos Silva, D, Silva Julian, G, Dinesh Singh, A, A Singh, J, Shahjahan Siraj, M, Reza Sivandzadeh, G, Yurievich Skryabin, V, Aleksandrovna Skryabina, A, Socea, B, Solmi, M, Sadegh Soltani-Zangbar, M, Song, S, Szerencs??s, V, Sz??cska, M, 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M., Adhikari, S., Advani, S. M., Afzal, M. S., Aghaie Meybodi, M., Ahinkorah, B. O., Ahmad, S., Ahmadi, A., Ahmadi, S., Ahmed, H., Ahmed, L. A., Ahmed, M. B., Al Hamad, H., Alahdab, F., Alanezi, F. M., Alanzi, T. M., Alhalaiqa, F. A. N., Alimohamadi, Y., Alipour, V., Aljunid, S. M., Alkhayyat, M., Almustanyir, S., Al-Raddadi, R. M., Alvand, S., Alvis-Guzman, N., Amini, S., Ancuceanu, R., Anoushiravani, A., Anoushirvani, A. A., Ansari-Moghaddam, A., Arabloo, J., Aryannejad, A., Asghari Jafarabadi, M., Athari, S. S., Ausloos, F., Ausloos, M., Awedew, A. F., Awoke, M. A., Ayana, T. M., Azadnajafabad, S., Azami, H., Azangou-Khyavy, M., Azari Jafari, A., Badiye, A. D., Bagherieh, S., Bahadory, S., Baig, A. A., Baker, J. L., Banach, M., Barrow, A., Berhie, A. Y., Besharat, S., Bhagat, D. S., Bhagavathula, A. S., Bhala, N., Bhattacharyya, K., Bhojaraja, V. S., Bibi, S., Bijani, A., Biondi, A., Bjorge, T., Bodicha, B. B. 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Subjects: Adult, MED/42 - IGIENE GENERALE E APPLICATA, IMPACT, colorectal cancer, Colorectal Neoplasm, GBD 2019 Colorectal Cancer Collaborators, HEREDITARY, Global Burden of Disease, Cancer screening, DISPARITIES, SDG 3 - Good Health and Well-being, Cancer treatment strategies, Risk Factors, Quality-Adjusted Life Year, COLON, Global studies, DALY, GBD, colorectal cancer, risk factors, Humans, Global Burden of Disease Study, Early Detection of Cancer, Hepatology, MORTALITY, Gastroenterology, Cancer incidence rates, Middle Aged, Cancer burden, SURVIVAL, SEX, GENDER, Quality-Adjusted Life Years, Colorectal Neoplasms, Human
Abstract: Correction to Lancet Gastroenterol Hepatol 2022; 7: 627-47. Lancet Gastroenterol Hepatol. 2022 Aug;7(8):704. doi: 10.1016/S2468-1253(22)00210-2. PMID: 35809605. Background: Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods: Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990-2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings: Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408-868 574) to 2·17 million (2·00-2·34), and deaths increased from 518 126 (493 682-537 877) to 1·09 million (1·02-1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3-23·0) per 100 000 to 26·7 (24·6-28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5-14·9) per 100 000 to 13·7 (12·6-14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7-320·7) per 100 000 to 295·5 (275·2-313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9-80·0] per 100 000), Monaco (60·7 [48·5-73·6] per 100 000), and Andorra (56·6 [42·8-71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0-37·1] per 100 000), Brunei (30·3 [26·6-34·1] per 100 000), and Hungary (28·6 [23·6-34·0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age
Published: 2022
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38. Global mortality associated with 33 bacterial pathogens in 2019

Author: Kevin S Ikuta, Lucien R Swetschinski, Gisela Robles Aguilar, Fablina Sharara, Tomislav Mestrovic, Authia P Gray, Nicole Davis Weaver, Eve E Wool, Chieh Han, Anna Gershberg Hayoon, Amirali Aali, Semagn Mekonnen Abate, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Sherief Abd-Elsalam, Getachew Abebe, Aidin Abedi, Amir Parsa Abhari, Hassan Abidi, Richard Gyan Aboagye, Abdorrahim Absalan, Hiwa Abubaker Ali, Juan Manuel Acuna, Tigist Demssew Adane, Isaac Yeboah Addo, Oyelola A Adegboye, Mohammad Adnan, Qorinah Estiningtyas Sakilah Adnani, Muhammad Sohail Afzal, Saira Afzal, Zahra Babaei Aghdam, Bright Opoku Ahinkorah, Aqeel Ahmad, Araz Ramazan Ahmad, Rizwan Ahmad, Sajjad Ahmad, Sohail Ahmad, Sepideh Ahmadi, Ali Ahmed, Haroon Ahmed, Jivan Qasim Ahmed, Tarik Ahmed Rashid, Marjan Ajami, Budi Aji, Mostafa Akbarzadeh-Khiavi, Chisom Joyqueenet Akunna, Hanadi Al Hamad, Fares Alahdab, Ziyad Al-Aly, Mamoon A Aldeyab, Alicia V Aleman, Fadwa Alhalaiqa Naji Alhalaiqa, Robert Kaba Alhassan, Beriwan Abdulqadir Ali, Liaqat Ali, Syed Shujait Ali, Yousef Alimohamadi, Vahid Alipour, Atiyeh Alizadeh, Syed Mohamed Aljunid, Kasim Allel, Sami Almustanyir, Edward Kwabena Ameyaw, Arianna Maever L Amit, Nivedita Anandavelane, Robert Ancuceanu, Catalina Liliana Andrei, Tudorel Andrei, Dewi Anggraini, Adnan Ansar, Anayochukwu Edward Anyasodor, Jalal Arabloo, Aleksandr Y Aravkin, Demelash Areda, Timur Aripov, Anton A Artamonov, Judie Arulappan, Raphael Taiwo Aruleba, Muhammad Asaduzzaman, Tahira Ashraf, Seyyed Shamsadin Athari, Daniel Atlaw, Sameh Attia, Marcel Ausloos, Tewachew Awoke, Beatriz Paulina Ayala Quintanilla, Tegegn Mulatu Ayana, Sina Azadnajafabad, Amirhossein Azari Jafari, Darshan B B, Muhammad Badar, Ashish D Badiye, Nayereh Baghcheghi, Sara Bagherieh, Atif Amin Baig, Indrajit Banerjee, Aleksandra Barac, Mainak Bardhan, Francesco Barone-Adesi, Hiba Jawdat Barqawi, Amadou Barrow, Pritish Baskaran, Saurav Basu, Abdul-Monim Mohammad Batiha, Neeraj Bedi, Melaku Ashagrie Belete, Uzma Iqbal Belgaumi, Rose G Bender, Bharti Bhandari, Dinesh Bhandari, Pankaj Bhardwaj, Sonu Bhaskar, Krittika Bhattacharyya, Suraj Bhattarai, Saeid Bitaraf, Danilo Buonsenso, Zahid A Butt, Florentino Luciano Caetano dos Santos, Jiao Cai, Daniela Calina, Paulo Camargos, Luis Alberto Cámera, Rosario Cárdenas, Muge Cevik, Joshua Chadwick, Jaykaran Charan, Akhilanand Chaurasia, Patrick R Ching, Sonali Gajanan Choudhari, Enayet Karim Chowdhury, Fazle Rabbi Chowdhury, Dinh-Toi Chu, Isaac Sunday Chukwu, Omid Dadras, Fentaw Teshome Dagnaw, Xiaochen Dai, Saswati Das, Anna Dastiridou, Sisay Abebe Debela, Fitsum Wolde Demisse, Solomon Demissie, Diriba Dereje, Msganaw Derese, Hardik Dineshbhai Desai, Fikadu Nugusu Dessalegn, Samuel Abebe A Dessalegni, Belay Desye, Kartik Dhaduk, Meghnath Dhimal, Sameer Dhingra, Nancy Diao, Daniel Diaz, Shirin Djalalinia, Milad Dodangeh, Deepa Dongarwar, Bezabih Terefe Dora, Fariba Dorostkar, Haneil Larson Dsouza, Eleonora Dubljanin, Susanna J Dunachie, Oyewole Christopher Durojaiye, Hisham Atan Edinur, Habtamu Bekele Ejigu, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Hassan El-Abid, Muhammed Elhadi, Mohamed A Elmonem, Amir Emami, Luchuo Engelbert Bain, Daniel Berhanie Enyew, Ryenchindorj Erkhembayar, Babak Eshrati, Farshid Etaee, Adeniyi Francis Fagbamigbe, Shahab Falahi, Aida Fallahzadeh, Emerito Jose A Faraon, Ali Fatehizadeh, Ginenus Fekadu, João C Fernandes, Allegra Ferrari, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Muktar A Gadanya, Abhay Motiramji Gaidhane, Balasankar Ganesan, Mesfin Gebrehiwot, Reza Ghanbari, Mohammad Ghasemi Nour, Ahmad Ghashghaee, Ali Gholamrezanezhad, Abdolmajid Gholizadeh, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Amador Goodridge, Damitha Asanga Gunawardane, Yuming Guo, Rajat Das Gupta, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Alemu Guta, Parham Habibzadeh, Atlas Haddadi Avval, Rabih Halwani, Asif Hanif, Md. 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Shakhmardanov, Mequannent Melaku Sharew, Athena Sharifi-Razavi, Purva Sharma, Rahim Ali Sheikhi, Ali Sheikhy, Pavanchand H Shetty, Mika Shigematsu, Jae Il Shin, Hesamaddin Shirzad-Aski, K M Shivakumar, Parnian Shobeiri, Seyed Afshin Shorofi, Sunil Shrestha, Migbar Mekonnen Sibhat, Negussie Boti Sidemo, Mustafa Kamal Sikder, Luís Manuel Lopes Rodrigues Silva, Jasvinder A Singh, Paramdeep Singh, Surjit Singh, Md Shahjahan Siraj, Samarjeet Singh Siwal, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Bogdan Socea, Damtew Damtew Solomon, Yimeng Song, Chandrashekhar T Sreeramareddy, Muhammad Suleman, Rizwan Suliankatchi Abdulkader, Saima Sultana, Miklós Szócska, Seyed-Amir Tabatabaeizadeh, Mohammad Tabish, Majid Taheri, Elahe Taki, Ker-Kan Tan, Sarmila Tandukar, Nathan Y Tat, Vivian Y Tat, Belay Negash Tefera, Yibekal Manaye Tefera, Gebremaryam Temesgen, Mohamad-Hani Temsah, Samar Tharwat, Arulmani Thiyagarajan, Imad I Tleyjeh, Christopher E Troeger, Krishna Kishore Umapathi, Era Upadhyay, Sahel Valadan Tahbaz, Pascual R Valdez, Jef Van den Eynde, H. Rogier van Doorn, Siavash Vaziri, Georgios-Ioannis Verras, Harimadhav Viswanathan, Bay Vo, Abdul Waris, Gizachew Tadesse Wassie, Nuwan Darshana Wickramasinghe, Sajad Yaghoubi, Gahin Abdulraheem Tayib Yahya Yahya, Seyed Hossein Yahyazadeh Jabbari, Arzu Yigit, Vahit Yiğit, Dong Keon Yon, Naohiro Yonemoto, Mazyar Zahir, Burhan Abdullah Zaman, Sojib Bin Zaman, Moein Zangiabadian, Iman Zare, Mikhail Sergeevich Zastrozhin, Zhi-Jiang Zhang, Peng Zheng, Chenwen Zhong, Mohammad Zoladl, Alimuddin Zumla, Simon I Hay, Christiane Dolecek, Benn Sartorius, Christopher J L Murray, Mohsen Naghavi, Ikuta, Kevin S, Swetschinski, Lucien R, Robles Aguilar, Gisela, Sharara, Fablina, Mestrovic, Tomislav, Gray, Authia P, Davis Weaver, Nicole, Wool, Eve E, Han, Chieh, Gershberg Hayoon, Anna, Aali, Amirali, Abate, Semagn Mekonnen, Abbasi-Kangevari, Mohsen, Abbasi-Kangevari, Zeinab, Abd-Elsalam, Sherief, Abebe, Getachew, Abedi, Aidin, Abhari, Amir Parsa, Abidi, Hassan, Aboagye, Richard Gyan, Absalan, Abdorrahim, Abubaker Ali, Hiwa, Acuna, Juan Manuel, Adane, Tigist Demssew, Addo, Isaac Yeboah, Adegboye, Oyelola A, Adnan, Mohammad, Adnani, Qorinah Estiningtyas Sakilah, Afzal, Muhammad Sohail, Afzal, Saira, Aghdam, Zahra Babaei, Ahinkorah, Bright Opoku, Ahmad, Aqeel, Ahmad, Araz Ramazan, Ahmad, Rizwan, Ahmad, Sajjad, Ahmad, Sohail, Ahmadi, Sepideh, Ahmed, Ali, Ahmed, Haroon, Ahmed, Jivan Qasim, Ahmed Rashid, Tarik, Ajami, Marjan, Aji, Budi, Akbarzadeh-Khiavi, Mostafa, Akunna, Chisom Joyqueenet, Al Hamad, Hanadi, Alahdab, Fare, Al-Aly, Ziyad, Aldeyab, Mamoon A, Aleman, Alicia V, Alhalaiqa, Fadwa Alhalaiqa Naji, Alhassan, Robert Kaba, Ali, Beriwan Abdulqadir, Ali, Liaqat, Ali, Syed Shujait, Alimohamadi, Yousef, Alipour, Vahid, Alizadeh, Atiyeh, Aljunid, Syed Mohamed, Allel, Kasim, Almustanyir, Sami, Ameyaw, Edward Kwabena, Amit, Arianna Maever L, Anandavelane, Nivedita, Ancuceanu, Robert, Andrei, Catalina Liliana, Andrei, Tudorel, Anggraini, Dewi, Ansar, Adnan, Anyasodor, Anayochukwu Edward, Arabloo, Jalal, Aravkin, Aleksandr Y, Areda, Demelash, Aripov, Timur, Artamonov, Anton A, Arulappan, Judie, Aruleba, Raphael Taiwo, Asaduzzaman, Muhammad, Ashraf, Tahira, Athari, Seyyed Shamsadin, Atlaw, Daniel, Attia, Sameh, Ausloos, Marcel, Awoke, Tewachew, Ayala Quintanilla, Beatriz Paulina, Ayana, Tegegn Mulatu, Azadnajafabad, Sina, Azari Jafari, Amirhossein, B, Darshan B, Badar, Muhammad, Badiye, Ashish D, Baghcheghi, Nayereh, Bagherieh, Sara, Baig, Atif Amin, Banerjee, Indrajit, Barac, Aleksandra, Bardhan, Mainak, Barone-Adesi, Francesco, Barqawi, Hiba Jawdat, Barrow, Amadou, Baskaran, Pritish, Basu, Saurav, Batiha, Abdul-Monim Mohammad, Bedi, Neeraj, Belete, Melaku Ashagrie, Belgaumi, Uzma Iqbal, Bender, Rose G, Bhandari, Bharti, Bhandari, Dinesh, Bhardwaj, Pankaj, Bhaskar, Sonu, Bhattacharyya, Krittika, Bhattarai, Suraj, Bitaraf, Saeid, Buonsenso, Danilo, Butt, Zahid A, Caetano dos Santos, Florentino Luciano, Cai, Jiao, Calina, Daniela, Camargos, Paulo, Cámera, Luis Alberto, Cárdenas, Rosario, Cevik, Muge, Chadwick, Joshua, Charan, Jaykaran, Chaurasia, Akhilanand, Ching, Patrick R, Choudhari, Sonali Gajanan, Chowdhury, Enayet Karim, Chowdhury, Fazle Rabbi, Chu, Dinh-Toi, Chukwu, Isaac Sunday, Dadras, Omid, Dagnaw, Fentaw Teshome, Dai, Xiaochen, Das, Saswati, Dastiridou, Anna, Debela, Sisay Abebe, Demisse, Fitsum Wolde, Demissie, Solomon, Dereje, Diriba, Derese, Msganaw, Desai, Hardik Dineshbhai, Dessalegn, Fikadu Nugusu, Dessalegni, Samuel Abebe A, Desye, Belay, Dhaduk, Kartik, Dhimal, Meghnath, Dhingra, Sameer, Diao, Nancy, Diaz, Daniel, Djalalinia, Shirin, Dodangeh, Milad, Dongarwar, Deepa, Dora, Bezabih Terefe, Dorostkar, Fariba, Dsouza, Haneil Larson, Dubljanin, Eleonora, Dunachie, Susanna J, Durojaiye, Oyewole Christopher, Edinur, Hisham Atan, Ejigu, Habtamu Bekele, Ekholuenetale, Michael, Ekundayo, Temitope Cyru, El-Abid, Hassan, Elhadi, Muhammed, Elmonem, Mohamed A, Emami, Amir, Engelbert Bain, Luchuo, Enyew, Daniel Berhanie, Erkhembayar, Ryenchindorj, Eshrati, Babak, Etaee, Farshid, Fagbamigbe, Adeniyi Franci, Falahi, Shahab, Fallahzadeh, Aida, Faraon, Emerito Jose A, Fatehizadeh, Ali, Fekadu, Ginenu, Fernandes, João C, Ferrari, Allegra, Fetensa, Getahun, Filip, Irina, Fischer, Florian, Foroutan, Masoud, Gaal, Peter Andra, Gadanya, Muktar A, Gaidhane, Abhay Motiramji, Ganesan, Balasankar, Gebrehiwot, Mesfin, Ghanbari, Reza, Ghasemi Nour, Mohammad, Ghashghaee, Ahmad, Gholamrezanezhad, Ali, Gholizadeh, Abdolmajid, Golechha, Mahaveer, Goleij, Pouya, Golinelli, Davide, Goodridge, Amador, Gunawardane, Damitha Asanga, Guo, Yuming, Gupta, Rajat Da, Gupta, Sapna, Gupta, Veer Bala, Gupta, Vivek Kumar, Guta, Alemu, Habibzadeh, Parham, Haddadi Avval, Atla, Halwani, Rabih, Hanif, Asif, Hannan, Md. Abdul, Harapan, Harapan, Hassan, Shoaib, Hassankhani, Hadi, Hayat, Khezar, Heibati, Behzad, Heidari, Golnaz, Heidari, Mohammad, Heidari-Soureshjani, Reza, Herteliu, Claudiu, Heyi, Demisu Zenbaba, Hezam, Kamal, Hoogar, Praveen, Horita, Nobuyuki, Hossain, Md Mahbub, Hosseinzadeh, Mehdi, Hostiuc, Mihaela, Hostiuc, Sorin, Hoveidamanesh, Soodabeh, Huang, Junjie, Hussain, Salman, Hussein, Nawfal R, Ibitoye, Segun Emmanuel, Ilesanmi, Olayinka Stephen, Ilic, Irena M, Ilic, Milena D, Imam, Mohammad Tarique, Immurana, Mustapha, Inbaraj, Leeberk Raja, Iradukunda, Arnaud, Ismail, Nahlah Elkudssiah, Iwu, Chidozie C D, Iwu, Chinwe Juliana, J, Linda Merin, Jakovljevic, Mihajlo, Jamshidi, Elham, Javaheri, Tahereh, Javanmardi, Fatemeh, Javidnia, Javad, Jayapal, Sathish Kumar, Jayarajah, Umesh, Jebai, Rime, Jha, Ravi Prakash, Joo, Tama, Joseph, Nitin, Joukar, Farahnaz, Jozwiak, Jacek Jerzy, Kacimi, Salah Eddine Oussama, Kadashetti, Vidya, Kalankesh, Laleh R, Kalhor, Rohollah, Kamal, Vineet Kumar, Kandel, Himal, Kapoor, Neeti, Karkhah, Samad, Kassa, Bekalu Getnet, Kassebaum, Nicholas J, Katoto, Patrick DMC, Keykhaei, Mohammad, Khajuria, Himanshu, Khan, Abba, Khan, Imteyaz A, Khan, Maseer, Khan, Md Nuruzzaman, Khan, Moien AB, Khatatbeh, Moawiah Mohammad, Khater, Mona M, Khayat Kashani, Hamid Reza, Khubchandani, Jagdish, Kim, Hanna, Kim, Min Seo, Kimokoti, Ruth W, Kissoon, Niranjan, Kochhar, Sonali, Kompani, Farzad, Kosen, Soewarta, Koul, Parvaiz A, Koulmane Laxminarayana, Sindhura Lakshmi, Krapp Lopez, Fiorella, Krishan, Kewal, Krishnamoorthy, Vijay, Kulkarni, Vishnutheertha, Kumar, Naveen, Kurmi, Om P, Kuttikkattu, Ambily, Kyu, Hmwe Hmwe, Lal, Dharmesh Kumar, Lám, Judit, Landires, Iván, Lasrado, Savita, Lee, Sang-woong, Lenzi, Jacopo, Lewycka, Sonia, Li, Shanshan, Lim, Stephen S, Liu, Wei, Lodha, Rakesh, Loftus, Michael J, Lohiya, Ayush, Lorenzovici, László, Lotfi, Mojgan, Mahmoodpoor, Ata, Mahmoud, Mansour Adam, Mahmoudi, Razzagh, Majeed, Azeem, Majidpoor, Jamal, Makki, Alaa, Mamo, Galana Ayana, Manla, Yosef, Martorell, Miquel, Matei, Clara N, McManigal, Barney, Mehrabi Nasab, Entezar, Mehrotra, Ravi, Melese, Addisu, Mendoza-Cano, Oliver, Menezes, Ritesh G, Mentis, Alexios-Fotios A, Micha, Georgia, Michalek, Irmina Maria, Micheletti Gomide Nogueira de Sá, Ana Carolina, Milevska Kostova, Neda, Mir, Shabir Ahmad, Mirghafourvand, Mojgan, Mirmoeeni, Seyyedmohammadsadeq, Mirrakhimov, Erkin M, Mirza-Aghazadeh-Attari, Mohammad, Misganaw, Abay Sisay, Misganaw, Awoke, Misra, Sanjeev, Mohammadi, Esmaeil, Mohammadi, Mokhtar, Mohammadian-Hafshejani, Abdollah, Mohammed, Shafiu, Mohan, Syam, Mohseni, Mohammad, Mokdad, Ali H, Momtazmanesh, Sara, Monasta, Lorenzo, Moore, Catrin E, Moradi, Maryam, Moradi Sarabi, Mostafa, Morrison, Shane Dougla, Motaghinejad, Majid, Mousavi Isfahani, Haleh, Mousavi Khaneghah, Amin, Mousavi-Aghdas, Seyed Ali, Mubarik, Sumaira, Mulita, Francesk, Mulu, Getaneh Baye B, Munro, Sandra B, Muthupandian, Saravanan, Nair, Tapas Sadasivan, Naqvi, Atta Abba, Narang, Himanshi, Natto, Zuhair S, Naveed, Muhammad, Nayak, Biswa Prakash, Naz, Shumaila, Negoi, Ionut, Nejadghaderi, Seyed Aria, Neupane Kandel, Sandhya, Ngwa, Che Henry, Niazi, Robina Khan, Nogueira de Sá, Antonio Tolentino, Noroozi, Nafise, Nouraei, Hasti, Nowroozi, Ali, Nuñez-Samudio, Virginia, Nutor, Jerry John, Nzoputam, Chimezie Igwegbe, Nzoputam, Ogochukwu Janet, Oancea, Bogdan, Obaidur, Rahman Md, Ojha, Vivek Anand, Okekunle, Akinkunmi Paul, Okonji, Osaretin Christabel, Olagunju, Andrew T, Olusanya, Bolajoko Olubukunola, Omar Bali, Ahmed, Omer, Emad, Otstavnov, Nikita, Oumer, Bilcha, P A, Mahesh, Padubidri, Jagadish Rao, Pakshir, Keyvan, Palicz, Tamá, Pana, Adrian, Pardhan, Shahina, Paredes, Jose L, Parekh, Utsav, Park, Eun-Cheol, Park, Seoyeon, Pathak, Ashish, Paudel, Rajan, Paudel, Uttam, Pawar, Shrikant, Pazoki Toroudi, Hamidreza, Peng, Minjin, Pensato, Umberto, Pepito, Veincent Christian Filipino, Pereira, Marco, Peres, Mario F P, Perico, Norberto, Petcu, Ionela-Roxana, Piracha, Zahra Zahid, Podder, Indrashi, Pokhrel, Nayanum, Poluru, Ramesh, Postma, Maarten J, Pourtaheri, Naeimeh, Prashant, Akila, Qattea, Ibrahim, Rabiee, Mohammad, Rabiee, Navid, Radfar, Amir, Raeghi, Saber, Rafiei, Sima, Raghav, Pankaja Raghav, Rahbarnia, Leila, Rahimi-Movaghar, Vafa, Rahman, Mosiur, Rahman, Muhammad Aziz, Rahmani, Amir Masoud, Rahmanian, Vahid, Ram, Pradhum, Ranjha, Muhammad Modassar Ali Nawaz, Rao, Sowmya J, Rashidi, Mohammad-Mahdi, Rasul, Azad, Ratan, Zubair Ahmed, Rawaf, Salman, Rawassizadeh, Reza, Razeghinia, Mohammad Sadegh, Redwan, Elrashdy Moustafa Mohamed, Regasa, Misganu Teshoma, Remuzzi, Giuseppe, Reta, Melese Abate, Rezaei, Nazila, Rezapour, Aziz, Riad, Abanoub, Ripon, Rezaul Karim, Rudd, Kristina E, Saddik, Basema, Sadeghian, Saeid, Saeed, Umar, Safaei, Mohsen, Safary, Azam, Safi, Sher Zaman, Sahebazzamani, Maryam, Sahebkar, Amirhossein, Sahoo, Harihar, Salahi, Saina, Salahi, Sarvenaz, Salari, Hedayat, Salehi, Sana, Samadi Kafil, Hossein, Samy, Abdallah M, Sanadgol, Nima, Sankararaman, Senthilkumar, Sanmarchi, Francesco, Sathian, Brijesh, Sawhney, Monika, Saya, Ganesh Kumar, Senthilkumaran, Subramanian, Seylani, Allen, Shah, Pritik A, Shaikh, Masood Ali, Shaker, Elaheh, Shakhmardanov, Murad Ziyaudinovich, Sharew, Mequannent Melaku, Sharifi-Razavi, Athena, Sharma, Purva, Sheikhi, Rahim Ali, Sheikhy, Ali, Shetty, Pavanchand H, Shigematsu, Mika, Shin, Jae Il, Shirzad-Aski, Hesamaddin, Shivakumar, K M, Shobeiri, Parnian, Shorofi, Seyed Afshin, Shrestha, Sunil, Sibhat, Migbar Mekonnen, Sidemo, Negussie Boti, Sikder, Mustafa Kamal, Silva, Luís Manuel Lopes Rodrigue, Singh, Jasvinder A, Singh, Paramdeep, Singh, Surjit, Siraj, Md Shahjahan, Siwal, Samarjeet Singh, Skryabin, Valentin Yurievich, Skryabina, Anna Aleksandrovna, Socea, Bogdan, Solomon, Damtew Damtew, Song, Yimeng, Sreeramareddy, Chandrashekhar T, Suleman, Muhammad, Suliankatchi Abdulkader, Rizwan, Sultana, Saima, Szócska, Mikló, Tabatabaeizadeh, Seyed-Amir, Tabish, Mohammad, Taheri, Majid, Taki, Elahe, Tan, Ker-Kan, Tandukar, Sarmila, Tat, Nathan Y, Tat, Vivian Y, Tefera, Belay Negash, Tefera, Yibekal Manaye, Temesgen, Gebremaryam, Temsah, Mohamad-Hani, Tharwat, Samar, Thiyagarajan, Arulmani, Tleyjeh, Imad I, Troeger, Christopher E, Umapathi, Krishna Kishore, Upadhyay, Era, Valadan Tahbaz, Sahel, Valdez, Pascual R, Van den Eynde, Jef, van Doorn, H. Rogier, Vaziri, Siavash, Verras, Georgios-Ioanni, Viswanathan, Harimadhav, Vo, Bay, Waris, Abdul, Wassie, Gizachew Tadesse, Wickramasinghe, Nuwan Darshana, Yaghoubi, Sajad, Yahya, Gahin Abdulraheem Tayib Yahya, Yahyazadeh Jabbari, Seyed Hossein, Yigit, Arzu, Yiğit, Vahit, Yon, Dong Keon, Yonemoto, Naohiro, Zahir, Mazyar, Zaman, Burhan Abdullah, Zaman, Sojib Bin, Zangiabadian, Moein, Zare, Iman, Zastrozhin, Mikhail Sergeevich, Zhang, Zhi-Jiang, Zheng, Peng, Zhong, Chenwen, Zoladl, Mohammad, Zumla, Alimuddin, Hay, Simon I, Dolecek, Christiane, Sartorius, Benn, Murray, Christopher J L, and Naghavi, Mohsen
Subjects: Male, Bacteria, Syndrome, Bacterial Infections, General Medicine, Global Health, Global Burden of Disease, Risk Factors, Sepsis, Humans, Female, Mortality, Child, Africa South of the Sahara
Abstract: Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.
Published: 2022

39. Ambiguous Melanocytic Tumors With Loss of 3p21

Author: Yeh, Iwei, Mully, Thaddeus W, Wiesner, Thomas, Vemula, Swapna S, Mirza, Sonia A, Sparatta, Alyssa J, McCalmont, Timothy H, Bastian, Boris C, and LeBoit, Philip E
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Human Genome, Cancer Genomics, Adolescent, Adult, Aged, Child, Chromosomes, Human, Pair 3, Comparative Genomic Hybridization, Female, Germ-Line Mutation, Humans, Male, Melanoma, Middle Aged, Skin Neoplasms, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Young Adult, melanoma, BAP1, Spitz nevus, melanocytic neoplasia, combined nevi, BRAF, Clinical Sciences, Pathology, Clinical sciences
Abstract: Germline loss-of-function mutations in BAP1 are associated with the development of cutaneous melanocytic tumors with some histopathologic characteristics seen in Spitz nevi. Similar melanocytic tumors occurring in a sporadic setting have been demonstrated to have biallelic loss of BAP1. In some of these sporadic tumors, loss of BAP1 occurs through mutation of 1 allele and genomic loss of the other. We screened our database of comparative genomic hybridization profiles of ambiguous melanocytic tumors to identify cases with a single genomic event involving loss of the BAP1 locus. The prevalence of tumors with a single genomic event involving loss of BAP1 was 6.7% in our study population. We further characterized the BAP1 status in 17 of these tumors with available additional material, confirming loss of BAP1 in all cases. We describe BAP1 loss in a blue nevus-like melanoma and further expand the histopathologic spectrum of spitzoid melanocytic neoplasms with BAP1 loss.
Published: 2014

40. Patient-Reported Outcome Results From the Open-Label Phase III AURELIA Trial Evaluating Bevacizumab-Containing Therapy for Platinum-Resistant Ovarian Cancer

Author: Stockler, Martin R, Hilpert, Felix, Friedlander, Michael, King, Madeleine T, Wenzel, Lari, Lee, Chee Khoon, Joly, Florence, de Gregorio, Nikolaus, Arranz, José Angel, Mirza, Mansoor Raza, Sorio, Roberto, Freudensprung, Ulrich, Sneller, Vesna, Hales, Gill, and Pujade-Lauraine, Eric
Subjects: Cancer, Rare Diseases, Ovarian Cancer, Clinical Research, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Doxorubicin, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Organoplatinum Compounds, Ovarian Neoplasms, Paclitaxel, Polyethylene Glycols, Self Report, Topotecan, Treatment Outcome, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: PurposeTo determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial.Patients and methodsPatients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data.ResultsBaseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions.ConclusionBevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer.
Published: 2014

41. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY)

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Joshua Abbas, Kasim Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Alison Abbott, Nabeel Abdallah, Ammar Abdelaziz, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Audrey Abdul, Basir Abdul, Siddiqui Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Abeer Ul Amna, Lynn Abel, Katrina Abernethy, Movin Abeywickrema, Chandra Abhinaya, Affyarsyah Abidin, Adebanke Aboaba, Abigail Aboagye-Odei, Christopher Aboah, Heba Aboelela, Hani Abo-Leyah, Karim Abouelela, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Ahmed Abousamra, Mona Abouzaid, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Rebecca Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yousuf Abusamra, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Faustina Acheampong, Prince Acheampong, Sarah Acheampong, Janet Acheson, Shiella Achieng, Andres Acosta, Rebecca Acquah, Catherine Acton, Jacqueline Adabie-Ankrah, Paul Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Marta Adamczyk, Carol Adams, Charlotte Adams, Daniel Adams, Kate Adams, Laura Adams, Nikkita Adams, Richard Adams, Tim Adams, Laura Adamu-Ikeme, Krishma Adatia, Kirsty Adcock, Lawrence Addai-Boampong, Afua Addo, Oluwatobi Adeagbo, Ade Adebiyi, Ogunlana Adedeji, Yewande Adegeye, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Femi W Adeoye, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Adedamola Adeyanju, Joyce Adeyemi, Tenifayo Adeyemo, Binay Adhikari, Shanti A Adhikari, Rina Adhikary, Adhikarla Aditya, Patience Adjepong, Gabrielle Adkins, Adnan Adnan, Marguerite Adriaanse, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Patricia Afrim, Felicia Akua Afriyie, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Laura Aguilar Jimenez, Jacqueline Afrakomah Agyekum, Kwame Agyen, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Afshan Ahmed, Ashar Ahmed, Asim Ahmed, Basheer A R Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Hanad Ahmed, Irshad Ahmed, Khaled Ahmed, Khalil Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rawya Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sana G Ahmed, Syed Ahmed, Syed H Ahmed, Roa Ahmed Ali, Bilal Ahmed Mohamud, Sana Ahmed, Sana Ahmer, Augustine Ahonia, Christine Aiken, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Bolutito Akinbiyi, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Mohammad Akram, Olugbenro Aktinade, Uzayr Akudi, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Adegoke Alabi, Narendra Aladangady, Mohamed Alafifi, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Albertus Albertus, Lorraine Albon, Angela Alcala, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Abdullah Aldesouki, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ram Maya Ale, Ana Alegria, Alison Alexander, Courtney Alexander, John Alexander, Peter D G Alexander, Julyan Al-fori, Laith Alghazawi, Osama Alhabsha, Bahij Al-Hakim, Rafil Alhameed, Mohammed Al-Hayali, Shams Al-Hity, Ali Ali, Amanda Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohamed Ali, Mohammad Ali, Muhammad S Ali, Nayab Ali, Oudai Ali, Ramla Ali, Sakina Ali, Syed Ali, Emilio Aliberti, Jade Alin, Abid Alina, Analyn Alipustain, Bachti Alisjahbana, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Abdullah Alkhudhayri, Moutaz Alkhusheh, Fiona Allan, Nataliya Allan, Alison Allanson, Robert Allcock, Eireann Allen, Jade Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Tania Allen, Abiola Alli, Kathryn Allison, Bethan Allman, Helen K Allsop, Lynne Allsop, David Allsup, Amal F T Almahroos, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Riyam Al-Sammarraie, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Fadia Alsheikh, Bashar Al-Sheklly, Sara Altaf, Amanda Alty, Mary Alvarez, Maria Alvarez Corral, Edward Alveyn, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Amel Amelia Ganefianty, Katharine Ames, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Badshah Amit, Amjad Amjad, Neelma Amjad, James Amoah-Dankwa, Victoria Amosun, Muhammad Amsal, Khaled Amsha, John Amuasi, Noelia Amutio Martin, Pugh Amy, Ann Anada, Atul Anand, Samantha Anandappa, Satya D Anantapatnaikuni, Ellen Anderson, Julie Anderson, Laura Anderson, Marina Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rebecca Anderson, Rory Anderson, Samantha Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Joyann Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Maldwyn Ansah, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Elena Apetri, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia F Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Samuel Archer, Simon Archer, Daniele Arcoria, Christian Ardley, Ana-Maria Arias, Oluwatoyin Aribike, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Jennifer Armistead, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Wendy Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Andrew Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Armena Arumaithurai, Ayush Arya, Rita Arya, Diptesh Aryal, Denisa Asandei, Adeeba Asghar, Malik Asghar, Arif Ashab, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Zakariya Ashfak, Ayesha Ashfaq, Abdul Ashish, Dawn Ashley, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Fiona J Ashworth, Rebecca Ashworth, Arshia Aslam, I Aslam, Suhail Aslam, Laura Aslett, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Abolaji Atomode, Brygitta Atraskiewicz, Abdul A Attia, Eva Attubato, Marie Attwood, Paula Aubrey, Zoltan Auer, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Hnin Wint Wint Aung, Ko Ko Aung, Kyaw Thu Aung, Nwe Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Malcolm Avari, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Abuzar Awadelkareem, Gabriel Awadzi, Mahmoud Awaly, Atia Awan, Aszad Aya, Eman Ayaz, John Maximilian Ayerh, Amanda Ayers, Jawwad Azam, Ahmed Azeem, Mohammed Azharuddin, Ammar Aziz, Ghazala Aziz, Imran Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Michel-Elie Bachour, Alisjahbana Bachti, Gina Bacon, Jenny Bacon, Bibi Badal, Aysha Badat, Maryuma Bader, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, Angela Bailey, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Lucy Bailey, Maria A Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Eilidh Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Danielle C Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Mark Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Ameet Bakhai, Nauman Bakhtiar, Panos Bakoulas, Dhanalakshmi Bakthavatsalam, Niranjan Balachandran, Andrea Balan, Prasath Balasingam, Theodosios Balaskas, Madhu Balasubramaniam, Nicola Balatoni, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Fiona Baldwin, Rebekah Baldwin-Jones, Nichola Bale, James Balfour, Matthew Ball, Robert Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Abeir Baltmr, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Santosh Baniya, Omar Bani-Saad, Harrison Banks, Luke Banks, Paul Banks, Claudia Bann, Helen Bannister, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Sharad Chandra Baral, Desislava Baramova, Russel Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Amanda Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Erandi Barker, Helen Barker, Joseph Barker, Leon Barker, Lesley Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Rory Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, Prince Gyenti Barning, William Barnsley, Andrew Barr, David Barr, James Barr, Charlotte Barr, Nina Barratt, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Sue Barrett, Esther Barrow, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, James Bartlett, Louise Bartlett, Shauna Bartley, Sandra Bartolmeu-Pires, Anna Barton, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Hannah Bashir, Archana Bashyal, Betsy Basker, Sudha Basnet, Buddha Basnyat, Ayten Basoglu, Alexander Basran, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Precious Basvi, Jireh A Batac, Vipula R Bataduwaarachchi, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Alice Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Tanveer Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Lee-Ann Bayo, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Kirsten Beadon, Philip Beak, Andy Beale, Kathy Beard, Jack Bearpark, Alanna Beasley, Sandee Beattie, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Sarah Beckley, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Sophia Beeby, Gail Beech, Michelle Beecroft, Nigel Beer, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Jessica Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer Bellamu, Mary Bellamy, Tammy Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Sarah Benkenstein, Tracey Benn, Ann Bennett, Caroline Bennett, Denise Bennett, Gillian Bennett, Kaytie Bennett, Kristopher Bennett, Lorraine Bennett, Miriam R Bennett, Sara Bennett, Karen Bennion, Gautham Benoy, Vivienne Benson, Andrew Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Frida Best, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Lila Nath Bhandari, Sangam Bhandari, Jennifer Bhanich Supapol, Aashutosh Bhanot, Ravina Bhanot, Swati Bhasin, Abdul Bhat, Prashanth Bhat, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Parminder Bhuie, M S Bhuiyan, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Prof Binh, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Sarah Bird, Mark Birt, Claire Bishop, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Mustapha Bittaye, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Virginia Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Cameron Blair, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Parry Blaxill, Katie Blaylock, Jane Blazeby, Natalie Blencowe, Ben Bloom, Jack Bloomfield, Angela Bloss, Alex Blowers, Samuel Blows, Hannah Bloxham, Susan Blrd, Louise Blundell, Andrew Blunsum, Mark Blunt, Tadhg Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Kwabena Appiah Boahen, Marilyn Boampoaa, Sarah Board, Boniface Bobie, Karen Bobruk, Pritesh N Bodalia, Neena Bodasing, Marianne Boden, Tanya Bodenham, Gabriele Boehmer, Marta Boffito, Katherine Bohanan, Kristyna Bohmova, Niamh Bohnacker, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed O Bokhari, Idan Bokobza, Ambrose Boles, Clare Bolger, Candice Bonaconsa, Charlotte Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Joseph Bonney, Lizzy Bonney, Lauren Booker, Sarah Boot, Matthew Boothroyd, Joanne Borbone, Naomi Borman, Samantha Bosence, Kirsty Bostock, Neil Botting, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Tarek Boumrah, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Tabitha Bowker, Helen Bowler, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Helen Bowyer, Aileen Boyd, Jenny Boyd, Laura Boyd, Nicola Boyer, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Abbey Bracken, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Clare Brady, Rebecca Brady, Shirin Brady, Pedro Braga Sardo, Denise Braganza, Megan Braithwaite, Susan Brammer, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Sophie Brattan, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Carolin Bresges, Catherine Bressington, Giovanna Bretland, Chris Brewer, Michael Bridgett, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Tracey Brigstock, Lutece Brimfield, Philip Brinksman, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Hannah Britton, Lauren Broad, Sarah Broadhead, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Mary Brodsky, Fiona Brogan, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Deirdre Brooking, Alison Brooks, Daniel Brooks, Jolene Brooks, Karen Brooks, Nicole Brooks, Philip Brooks, Rachel Brooks, Samuel Brooks, Sophie Brooks, Malcolm Broom, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Ammani Brown, Andrew Brown, Ashley Brown, Caitlin Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Jo Brown, Louise Brown, Niall Brown, Nicola Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Andrei Brunchi, Nigel Brunskill, Alan Brunton, Margaret Brunton, Meera Bryant, Emma Bryden, Hannah Brzezicki, April Buazon, Maya H Buch, Ruaridh Buchan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Lisa Buck, Matthew Buckland, Clare Buckley, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, Alex Budds, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Kate Bull, Rhian Bull, Thomas Bull, Emily Bullock, Susan Bullock, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Oliver Burbidge, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Richard Burgess, Sophia Burgess, Erlina Burhan, Hasan Burhan, Hannah Burke, Kerry Burke, Adrian Burman, Sara Burnard, Caroline Burnett, Sharon Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Kiki Burns, Daniel Burrage, Kate Burrows, Claire Burston, Anna Burton, Ben Burton, Fiona Burton, Helen Burton, Matthew Burton, Mannaria Butar butar, Deborah Butcher, Aaron Butler, Emily Butler, Jessica Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Jenny Butler, Al-Tahoor Butt, Massawer Butt, Mohammad M Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Hannah Bye, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Amanda Cabandugama, Luisa Cabrero, Simone Caddy, Ruth Cade, Anthony Cadwgan, Zhen Cahilog, Ajeng Cahyareny, Donna Cairney, James Calderwood, Darren Caldow, Emily Cale, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Karen Campbell, Marion Campbell, Mark Campbell, Rachael Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Lisa Canclini, Shaula M Candido, Janie Candlish, Cielito Caneja, Alexandra Cann, Johnathon Cann, Ruby Cannan, Abigail Cannon, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Ebnier Canonizado, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Richard Capstick, Thomas Capstick, Catalin Caraenache, Aimee Card, Mary Cardwell, Charles Carey, Rachel Carey, Simon Carley, Ffion Carlin, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Jodi Carpenter, Sharon Carr, Anna Carrasco, Zoe Carrington, Amy Carroll, Anne Carroll, Paul Carroll, Rachel Carson, Cindy Cart, Emma Carter, Jonathan Carter, Michael Carter, Natasha Carter, Paul Carter, Penny Carter, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Lotoyah Carty, Jaime Carungcong, Charlotte Carver, Emma Carver, Rachel Carver, Susan Casey, Annie Cassells, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Anelise Catelan Zborowski, Susanne Cathcart, Katrina Cathie, Darwin Catibog, Christine Catley, Laura Catlow, Matthew Caudwell, Anna Cavazza, Ashleigh Cave, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Kay Cawthorne, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, Cyril J Chacko, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, Petya Chalakova, Bimal Sharma Chalise, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Jay Marie Chan, Kawai Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H S Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Yvonne Chang, Ho Quang Chanh, Grace Chaplin, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Matthew Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Sam Charlton, Kevin Chatar, Calvin Chatha, Debra Chatterton, Ritesh Chaube, Muhammad Y N Chaudhary, Netra B Chaudhary, Iram Chaudhry, Zain Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi S Chauhan, Alexander Chavasse, Nicola Chavasse, Vipal Chawla, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Floria Cheng, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Mary Cherrie, Helen Cheshire, Chee Kay Cheung, Elaine Cheung, Kayan Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Moses Chikungwa, Zviedzo A Chikwanha, Gemma Chilcott, Sam Chilcott, Alison Chilvers, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Ezomike Chinonso, Chloe Chin-Saad, Margaret Chirgwin, Heather Chisem, Claire Chisenga, Catherine Chisholm, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Laura Chiverton, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Meena Chopra, Michelle Chopra, Vandana Choudhary, Omur Choudhury, Sarah Choudhury, Bing-Lun Chow, Mahibbur Chowdhury, Shahid Chowdhury, Angela Chrisopoulou, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Georgios Christoforou, Thereza Christopherson, Anna Christou, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Yee Chung, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Bridget Clancy, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Emma Clark, Felicity Clark, Gabrielle Clark, James Clark, Julia Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Martyn Clark, Matthew Clark, Nicola Clark, Patricia Clark, Richard Clark, Thomas Clark, Tonia Clark, Zoe Clark, Alison Clarke, Andrea Clarke, Jude Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Louis Claxton, Kate Clay, Catherine Clayton, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Bethan Clearyb, Chris Cleaver, Rose Cleeton, Ian Clement, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Sue Clenton, Sheryl Cliff, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Vincent Clubb, Samantha Clueit, Lisa Clutterbuck, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Laura Cockayne, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, David Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Garry Coleman, Matt Coleman, Nick Coleman, Holly Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Kathleen Collie, Alexandra Collier, Danielle Collier, Dawn Collier, Heather Collier, Terry Collingwood, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Kayleigh Collins, Megan Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Alison Comerford, Dónal Concannon, Alison Condliffe, Robin Condliffe, Emma Connell, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Emma Connor, Antonia Conroy, Kevin Conroy, Veronica Conteh, Rory Convery, Francesca Conway, Grainne Conway, Rhiannon Conway, Robert Conway, Jo-Anna Conyngham, Amanda Cook, Amber Cook, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Martin Cook, Sarah Cook, Danielle Cooke, Graham Cooke, Hannah Cooke, Justin Cooke, Katrina Cooke, Tim Cooke, Vikki Cooke, Adele Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Samantha Cooray, Thomas Cope, Sinead Corbet, Carolyn Corbett, Ailsa Corbishley, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Aisling Corr, Mirella Corredera, Ruth Corrigan, P Corry, Rita Corser, Jon Cort, Denise Cosgrove, Tracey Cosier, Patricia Costa, Telma Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, George Couch, Martina Coulding, Andrew Coull, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Amanda J Coutts, Alexander Cowan, Elena Cowan, Richard Cowan, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Emma Cox, Giles Cox, Helen Cox, Karina Cox, Miriam Cox, Karen Coy, Andrea Cradduck-Bamford, Hannah Craig, Jayne Craig, John Craig, Victoria Craig, Felicity Craighead, Matthew Cramp, Hayley Cranston, Sheetal S Crasta, Jacolene Crause, Angie Crawford, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Amanda Creaser-Myers, Joanne Cremona, Saveria Cremona, Anna Crepet, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Jennifer Crooks, Harriet Crosby, Elizabeth Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Lorraine Cullen, Gillian Cummings-Fosong, Victoria Cunliffe, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Susan Currie, Susie Currie, Jonathan Curtis, Katrina Curtis, Matthew Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Jennifer Cuthill, Sean Cutler, Sarah Cutts, Marta Czekaj, Patrycja Czylok, Shane D'Souza, Joana da Rocha, Mohammed Dafalla, Andrew Dagens, Helen Daggett, Jacqui Daglish, Sandeep Dahiya, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Susan Dale, Jolyon Dales, Umberto D'Alessandro, Helen Dalgleish, Helen Dallow, Carlo D'aloia, Dermot Dalton, Morag Dalton, Zoe Daly, Mansi Damani, Eleanor Damm, Akila Danga, Joanne Dangerfield, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Kwaku Gyasi Danso, Sandra Danso-Bamfo, Quang Tung Dao, Suzanne Darby, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Kate Darlington, Sarah Darnell, Thomas Darton, Guledew Darylile, Avisnata Das, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Vaishali Dave, Emily Davenport, Mark Davey, Miriam Davey, Molly Davey, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Alison Davies, Amanda Davies, Amy Davies, Angela Davies, Bethan Davies, Caroline Davies, Carolyn Davies, Catrin Davies, Dawn Davies, Drew Davies, Elaine Davies, Elinor Davies, Ellie Davies, Ffyon Davies, Gwyneth Davies, Helen Davies, Jennifer Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Llinos Davies, Louisa Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sally Davies, Sarah Davies, Simon Davies, Sue Davies, Alison Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Andrea Davis-Cook, Alexander Davison, Christine Dawe, H Dawe, Mark Dawkins, Angela Dawson, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Lucinda Dawson, Mike Dawson, Susan Dawson, Tom Dawson, Isla Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy N Day, Jamie D'Costa, Parijat De, Pradip De, Duneesha de Fonseka, Toni de Freitas, Pamela De Los Santos Dominguez, Roberta De Pretto, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Phillip De Souza, Anthony De Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Gonzalo De-La-Cedra, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Alexandra Dent, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Usha Devkota, Debbie Devonport, Matthew Devonport, Prakash Dey, Vishal Dey, Rogin Deylami, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Ankush Dhariwal, Dawpadee Dharmasena, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Syra Dhillon, Meghnath Dhimal, Dipali Dhiru, Trupti Dhorajiwala, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Mohammed Dibas, Debbie Dickerson, Pamela Dicks, Matt Dickson, Stuart Dickson, J Digby, Ronneil Digpal, Sean Dillane, Sarah Diment, Paul Dimitri, Georgios Dimitriadis, Sajeel Din, Thai H Dinh, Thi T T Dinh, Alex Dipper, Sabiq Dipro, Laura Dirmantaite, Lorelle Dismore, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Preeti Diwan, Caroline Dixon, Giles Dixon, Kate Dixon, Brice Djeugam, Sipho Dlamini, Petr Dlouhy, Andrea D'Mello, Paul Dmitri, Thi Tien Do, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, Jacqueline Dodd, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Conor Doherty, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Katie Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Phu Khiem Dong, Martha Donkor, Sinead Donlon, Joanne Donnachie, Eilish Donnelly, Ronan Donnelly, Phil Donnison, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Emma Dooks, Reece J Doonan, Rogier Van Doorn, Grainne Doran, Rachael Dore, Kane Dorey, Sharon Dorgan, Kataryna Dos Santos, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Isabelle Doss, Theonymfi Doudouliaki, Andrew Dougherty, Jill Doughty, Katie Douglas, Jonathan Douse, Allyn Dow, Lucy Dowden, Michelle Dower, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Robert Downey, Caroline Downing, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Anthony Drexel, Celine Driscoll, Helena Drogan, Odysseas Drosos, Graham Drummond, Katie Drury, Kay Druryk, Ronald Druyeh, Jack Dryburgh-Jones, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Stephen Duberley, Paige K Duckenfield, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Heather Duffy, Helen Duffy, Katharine Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Rauand Duhoky, Janice Duignan, Jennifer Dulay, Simon Dummer, Alexis Duncan, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, Holly Duncan, Robert Duncan, Stephanie Dundas, Do Van Dung, Aileen Dunleavy, Julia Dunleavy, Alessia Dunn, Charlotte Dunn, Damian Dunn, Laura Dunn, Paul Dunn, Charlene Dunne, Karen Dunne, Fiona Dunning, Aidan Dunphy, Tran Thi Hai Duong, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Leanne Durdle, Natalie Duric, Alison Durie, Emily Durie, Samuel Durogbola, Chris Durojaiye, Laura Durrans, Katie Durrant, Hannah Durrington, Iheukwumere Duru, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Dennis Dwomoh Nkrumah, Ellen Dwyer, Zara Dyar, Claudia Dyball, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Lauren Eadie, Rebekah Eadie, Laura Eagles, Beena Eapen, Naomi Earl, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Amy Easthope, Fraser Easton, Jack Easton, Patrick Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Alison Eccles, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Mary Edmondson, Tracy Edmunds, Abby Edwards, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Martin Edwards, Sophie Edwards, Jenny Eedle, Aline Eggink, Dawn Egginton, Sam Eggleston, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Nagla Elashhar, Lisa Elawamy, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Emma Eldridge, Diana Eleanor, Uchenna Elenwa, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Mohamed A A Elhadi, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura N Ellerton, Lucy Elliot, Amy Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Sian Elliott, Annie Ellis, Christine Ellis, Kaytie Ellis, Leila Ellis, Rupert Ellis, Tak-Yan Ellis, Yvette Ellis, Alison C Ellwood, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed El-Naggar, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Mohammed A S A Elsayed, Sally El-Sayeh, Hana El-Sbahi, Mohammad Elsebaei, Tarek Elsefi, Karim El-Shakankery, Alguili Elsheikh, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Anna Emery, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Dickson Enenche, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Peter Eskander, Hanif Esmail, Fatheha Essa, Brynach Evans, Chris Evans, Debra Evans, E Evans, Emrys Evans, Gail Evans, Gareth Evans, Isabel Evans, Jack Evans, Jacqueline Evans, Jennifer Evans, John Evans, Jolanta Evans, Lisa Evans, Lynn Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Sharon Evans, Sian Evans, Teriann Evans, Tomos Evans, Caroline Everden, Serenydd Everden, Lynette Every, Hayley Evison, Lynsey Evison, Chiamaka Ezenduka, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Ian Fairbairn, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Ayaan Farah, Muna Farah, Qayyum Farah, Nowin Z Fard, Leila Fares, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Holly Farr, Aaron Farrell, Barbara Farrell, Fayed Farrukh, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Suman Fathima, Nibah Fatimah, Maria Faulkner, Saul N Faust, Clair Favager, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Aisthath Fazleen, Simon Fearby, Connie Fearnley, Alex Feben, Federico Fedel, Daria Fedorova, Christopher Fegan, Mae Felongo, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Ruth Fennelly, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Gloria Ferenando, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Jaime Fernandez Roman, Callum J Fernando, Jessica Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Sheldon Ferron, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Santos Filipa, Sarah A Filson, Shona Finan, Sarah Finbow, Deborah J Finch, Joanne Finch, Laurie Finch, Simon Finch, Spencer Finch, Natalie Fineman, Jim Finlayson, Lauren Finlayson, Adam Finn, Joanne Finn, Dylan Finnerty, Clare Finney, Deborah Finucane, Sofia Fiouni, Jo Fiquet, Promise Firi, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Carolyn Fitton, Felicity Fitzgerald, Fiona Fitzgerald, Karen Fitzjohn, Jan Flaherty, Michael Flanagan, Charles Flanders, Nikolaos Flaris, Gail Fleming, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Anna Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Fiona Flett, Karen Flewitt, Sarah Flockhart, Christopher Flood, Ian Floodgate, Jonathan Flor, Vincent Florence, Mary Flowerdew, Sharon Floyd, Margaret J Flynn, Rachel Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Paul Foley, Linda Folkes, Tracey Fong, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Helen R Foot, Jayne Foot, Jane Forbes, Amber Ford, Jamie Ford, Imogen Fordham, Jennifer Foreman, Matthew Forester, Mohammad Forkan, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Abigail Forsyth, Julian Forton, Conrad Foster, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Natasha Fowkes, Emily Fowler, Robert Fowler, Stephen Fowler, Amy Fox, Claire Fox, Heather Fox, Jonathan Fox, Laura Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Eva Fraile, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Siobhan Franklin, Catherine Fraser, Andi Fratila, Sharon Frayling, Martyn Fredlund, Anna Freeman, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Thomas French, Karen Freshwater, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Andrzej Frygier, Bridget Fuller, Liz Fuller, Lucy Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Zoë Gabriel, Hadiza Gachi, Sophie Gaffarena, Sarah Gage, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Babita Gajmer, Zacharoula Galani, Christopher Gale, Hugo Gale, Linda Gale, Rebecca Gale, Swetha Gali, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Feroze Gallam, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Anna Galvin, Victoria Galvis, Gareth Gamble, Laura Gamble, Liz Gamble, Brian Gammon, Chien N Gan, Muhammad B Ganaie, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Thenugan Ganeshanathan, Saibal Ganguly, Abrar Gani, Pauline Ganley, Ukraina Garcia, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Louis Gardner, Mark Garfield, Atul Garg, Isha Garg, Nathan Garlick, Daniel Garner, Justin Garner, Lucie Garner, Zoe Garner, Rosaline Garr, Kathryn A Garrero, Manisha Gartaula, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Sophie Gayle, Catherine Geddie, Ian Gedge, Sarah Gee, Fartuun Geele, Kalaichelvi Geerthan, Minnie Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Neal Gent, Susan Gent, Natalie Geoghegan, Aparna George, Bini George, Sam George, Susan George, Tina George, Valerie P George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Siobhan Gettings, Hisham Ghanayem, Bijan Ghavami Kia, Shaista Ghazal, Anca Gherman, Alison Ghosh, Dipansu Ghosh, Justin Ghosh, Subhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Chris Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Jamie Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Mary Gigi, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, James Gilham, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Lesley Gilmour, Louis Ginn, Franciscus Ginting, Theodora Giokanini-Royal, Anna Gipson, Barbie Giri, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Eleanor Glenday, Ana Glennon, Jodie Glossop, John Glover, Kyle Glover, Michelle Glover, Jan Glover Bengtsson, Deborah Glowski, Sharon Glynn, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Sarah Godlee, Emma Godson, Gillian Godwin, Sukanya Gogoi, Aiky Goh, Manjinder Gohel, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Vicky Goodall, Bob Goodenough, Anna Goodfellow, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Chris Gordon, Sally Gordon, Robin Gore, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Maria Gorniok, Diana Gorog, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Nicole Gould, Susan Gould, Charlotte Goumalatsou, Lysander Gourbault, Abha Govind, Rajesh Govindan, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Cheryl Graham, Clive Graham, Jonathan Graham, Justin Graham, Libby Graham, Rachel Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Kirstie Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Glaxy Gray, Jackie Gray, Karen Gray, Nicola Gray, Roxanne Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Amy Green, Amy S Green, Charlotte Green, Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Jack Grenville, Jo Gresty, Susan Grevatt, Glaxy Grey, Samuel Gribben, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sandra Griffiths, Sarah Griffiths, Scott Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Evelina Grobovaite, Dorothy Grogono, Clarissa Grondin, Rachel Groome, Pauline Grose, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Jacinta Guerin, Sharazeq 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Hale, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alaina Halim, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Laura Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Jackie Halliday, Akmal Hallman, Heather Halls, Maryam Hamdollah-Zadeh, Ifedadepo A Hamed-Adekale, Bilal Hameed, Mohammed Hameed, Raph L Hamers, Imran Hamid, Mohamad Hamie, Raymond Hamill, Bethany Hamilton, Fergus Hamilton, Gus Hamilton, Leigh Hamilton, Melanie Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Emily Hammond, Leah Hammond, Sally Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, James A Hampson, Jude Hampson, Lucy Hampson, Lisa Hamzah, Jenny Han, Ozan Hanci, Sadiyah Hand, Lala Handayani, Jasmine Handford, Soran Handrean, Nina K Handzewniak, Sarah Haney, Vu Thi Kim Hang, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Helena Hanratty, Daniel Hansen, Anita Hanson, Ashley Hanson, Helen Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Ala Haqiqi, Monjurul Haque, Henry Harcourt, Lesley Harden, Zoe Harding, Simon Hardman, Marc Hardwick, Gareth Hardy, Joanna Hardy, Yasmine Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, James Hargraves, Carolyn Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Heather Harper, James Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Kate Harrington, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, Sophie Harris, David Harrison, Laura Harrison, Melanie Harrison, Olakunbi A Harrison, Rachael Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Jessica Hartley, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Alice Harvey, Angela Harvey, Anna Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Zoe Harzeli, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Jack Haslam, Zena Haslam, Grace Hasnip, Adil Hassan, Ali Hassan, Amro Hassan, Awab Hassan, Zeinab Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Sarah Hathaway-Lees, Jonathan Hatton, Jennifer Hau, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Lydia Hawker, Annie Hawkins, Joe Hawkins, Nancy Hawkins, W John Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Alasdair W Hay, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Carole Hays, Sarah Haysom, James Hayward, Patrick Haywood, Hazel Haywood Hasford, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Jessica L Healy, Amy Hearn, David Heasman, Angela Heath, Debbie Heath, Rowan Heath, Diane Heaton, Adam Heavens, Kerry Hebbron, Catherine Heckman, Gemma Hector, Sadie Heddon, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Richard Heinink, Rajdeep Heire, Ingvild Helgesen, Joanne Hemingway, Ulla Hemmila, Beth Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Eilidh Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Lucas E Hermans, Fe Marie Hernandez, Emma Heron, Lisa Heron, William Herrington, Emilia Heselden, Peta Heslop, Tracey Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, 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Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Catherine Houghton, Kathryn Houghton, Rebecca Houlihan, Kay Housely, Hamish Houston, Roseanna Hovvels, Lee How, Laura Howaniec, Joanne Howard, Kate Howard, Laura Howard, Linda Howard, Lucy Howard, Megan Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Louise Howard-Sandy, Serena Howe, Alice Howell, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Ruth Howman, Josh Hrycaiczuk, Hein Htet, Naing Z Htoon, Su Htwe, Ying Hu, Chiang O H Huah, Sylvia Huang, Kelly Hubbard, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Suzanne Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Caitlin Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Martin Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, 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McCann, Erin McCann, Alexandra McCarrick, Brendan McCarron, Eoghan McCarthy, Michelle McCarthy, Natalie McCarthy, Sinead McCaughey, Tara McClay, Beverley McClelland, Declan McClintock, Michael McCloskey, Kirsten McCollum, Alasdair McCorkindale, Patricia McCormack, Jacqueline McCormick, Jake McCormick, Wendy McCormick, Paul McCourt, Jame McCrae, Sharon McCready, Gordan McCreath, Helen McCreedy, Claire McCue, Iain J McCullagh, Liz McCullagh, Megan McCullagh, Conor McCullough, Katherine McCullough, Nicola McCullough, Sarah McCullough, Fiona McCurrach, John McDermott, Paula McDermott, Rory McDermott, Katharine McDevitt, Helen McDill, Basil McDonald, Carly McDonald, Claire McDonald, Debbie McDonald, Rob McDonald, Sam McDonald, Damhnaic McDonald, Natasha McDonnell, Catherine McDougall, Lilly McDougall, Rowan McDougall, Irene McEleavy, Fred McElwaine, Julie McEntee, Evanna McEvoy, Claire McEwan, Ruth McEwen, Margaret McFadden, Denise McFarland, Margaret McFarland, Rachel McFarland, Joe McFlynn, Erin McGarry, Lorcan McGarvey, Alex McGeachan, Frederick McGee, Laura McGenily, Clodagh McGettigan, Michael McGettrick, Christopher McGhee, Fiona McGill, Sarah McGinnity, Neil McGlinchey, Phil McGlone, Deborah McGlynn, Claire McGoldrick, Clare McGoldrick, Elizabeth McGough, Christopher McGovern, Roisin McGovern, Angela McGowan, Anne McGown, Brendan McGrath, Amanda McGregor, Annemarie McGregor, Michael P McGuigan, Heather McGuinness, Sean McGuire, Tara McHugh, Caroline McInnes, Neil McInnes, Jerome McIntosh, Karen McIntyre, Mhairi McIntyre, Lorna McKay, Conor P McKeag, Jacqueline McKeane, Madeleine McKee, Joseph McKeever, Judith McKenna, Shirley McKenna, Mary McKenzie, Donogh McKeogh, Caroline McKerr, Anthony M McKie, Hayley Mckie, Laura Mckie, Gerard McKnight, Heather McLachlan, Andrew McLaren, Barbara McLaren, Nicola McLarty, Danielle Mclaughlan, Maria McLaughlin, James McLay, Mary McLeish, Tina McLennan, Stewart McLure, Anne Marie McMahon, Genevieve McMahon, Mike McMahon, Stephen McMahon, Terence McManus, Moyra McMaster, P McMaster, Paddy McMaster, Faye Mcmeeken, Samuel McMeekin, Nicola McMillan, Katherine McMillen, Jason McMinn, Liam McMorrow, Heather McMullen, Christopher McMurran, Helen McNally, Fiona McNeela, Lynne McNeil, Claire McNeill, Jessica McNeill, Shea McNeill, Una McNelis, Melanie McNulty, Roisin McNulty, Christopher McParland, Mark McPhail, Alison McQueen, Anna McSkeane, Denise McSorland, Therese McSorley, Gini McTaggart, Jacqueline McTaggart, Joanna Mead, Paul Mead, Emma Meadows, Olivia Meakin, Ben Mearns, Claire Mearns, Kim Mears, William Mears, Manjula Meda, Ayren Mediana, Ross Medine, Thomas Medveczky, Sharon Meehan, Emily Meeks, Abbi Megan, Nevan Meghani, Salim Meghjee, Sharon Megson, Amina Mehar, Mehr N Mehmood, Rohan Mehra, Rohan Mehta, Graeme Meintjes, James Meirill, James Meiring, Rayane Mejri, Ellen Mekonnen, Sabina Melander, Adriana-Stefania Melinte, Jennifer Mellersh, Lucy Melling, Christie Mellish, Francesca Mellor, Joe S 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Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Omaisa Mushtaq, Sohmal Musini, Ahmed M M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Naveed Mustfa, Zhain Mustufvi, Callum Mutch, Rachel Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, James S Myerson, Khin Swe Myint, Yadee Myint, Georgina Mynott, Libor Myslivecek, Patricia Nabayego, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Behzad Nadjm, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Widya Naftalia, Thapas Nagarajan, Leah Naglik, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Deborah Nakiboneka-Ssenabulya, Sri Nallapareddy, Soum 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Madeleine Trowsdale Stannard, Nigel Trudgill, Robert Truell, Nick Truman, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Tan Tsawayo, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Merika Tsitsi, Simon Tso, Natasha Tucker, Sally Tucker, Stephanie Tucker, Daisy E Tudor, Aisha Tufail, Jess Tuff, Jemma Tuffney, Redmond Tully, Tulus Tulus Satriasih, Grace Tunesi, Killiam Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Georgina Turner, Kate Turner, Kelly Turner, Kim Turner, Lucy Turner, Lynne C Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Sarah Turner, Victoria Turner, Ian Turner-bone, Sharon Turney, Jon Turvey, Conor Tweed, David Tweed, Rebecca Twemlow, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Amanda Tyler, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Ioannis Tzinieris, A Wahid Uddin, Mohammad S Uddin, Ruhama Uddin, Ruzena Uddin, Jacinta Ugoji, Edith N Ukaegbu, Mazhar Ul Haq, Waqar Ul Hassan, Zia Ul-Haq, Salamat Ullah, Sana Ullah, Sanda Ullah, Ju Um, Athavan Umaipalan, Anil Umate, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Ben Ummat, Emma Underhill, Charlotte Underwood, Jonathan Underwood, Adam Unsworth, Veerpal Uppal, Veerpal S Uppal, Gerry Upson, Masood Ur Rasool, Alison Uriel, Sebastian Urruela, Hiromi Uru, Jess Usher, Miranda Usher, Rebecca Usher, Alexandra Usher-Rea, Andrew Ustianowski, Effua Usuf, Febriansyah Nur Utomo, Hiromi Uzu, Linda C Vaccari, Uddhav Vaghela, Abhay Vaidya, Denny Vail, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Pramodh Vallabhaneni, Nick Vallotton, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Sarah Van Blydenstein, Lucia van Bruggen, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne van Koutrik, Alexander Van Loggerenberg, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Piyush Vanmali, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Anna-Nektaria Varouxaki, Resti Varquez, Valeria Vasadi, Olivia Vass, Katherine Vassell, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Sue Vaughan, Heloyes Vayalaman, Darini Vayapooree, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Aravind Velugupati, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Michelle Venter, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Liberty Verueco, Jerik Verula, Anna Veterini, Natalie Vethanayagam, Shambavi Vettikumaran, Lucy Veys, Carinna Vickers, Saji Victor, SImpson Victoria, Celine P Vidaillac, Jennifer Vidler, Bavithra Vijayakumar, Vinod W Vijayaraghavan Nalini, Brigita Vilcinskaite, Alicija Vileito, Neringa Vilimiene, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Olivia Vincent, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Martina Vitaglione, Karunakaran Vithian, Sorice Vittoria, Sankkita Vivekananthan, Elena Vlad, Ben Vlies, Linda von Oven, Claire Vooght, Kim Thi Vu Thai, Kritchai Vutipongsatorn, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Phillip Wade, Jonathan Wadsley, Kirsten Wadsworth, Syed E I Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Alicia Waite, Rachel Wake, Alice Wakefield, William Wakeford, Fiona Wakinshaw, Emma Waldeck, Andrew Walden, Lorna Walding, Alexandria Waldron, Joanne Waldron, Emma Wales, Batool Wali, Danielle Walker, Gemma Walker, Harriet Walker, Ian Walker, Kevin Walker, Kim Walker, Lauren Walker, Linda Walker, Lynne Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Sara Walker, Susan Walker, Gillian Wallace, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Matthew Wallis, Emma Walmsley, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Maisie Walton, Michael Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Junita Wanda, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Shentong Wang, Deborah Warbrick, Samantha Warburton, Christopher Ward, Deborah Ward, Emma Ward, Hannah Ward, Janice Ward, Joanna Ward, Luke Ward, Nicola Ward, Rachael Ward, Thomas Ward, Tom Ward, Scott A Warden, Gibril Wardere, Steve Wardle, Hassan Wardy, Gareth Waring, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Rebecca Warren, Yolanda Warren, Davina Warrender, Hannah Warren-Miell, Adilia Warris, Gill Warwick, Helen Wassall, Sean Wasserman, Elizabeth Wasson, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Abigail Watkin, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Abigail Watson, Adam J R Watson, Ekaterina Watson, Eleanor Watson, Felicity Watson, J G R Watson, Louisa Watson, Paul Watson, Rebecca Watson, Robert Watson, Kathleen Watson, Malcolm Watters, Donna Watterson, Khairiah Wattimena, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Matthew Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Chloe Webb, Claire Webb, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Jemma Webster, Tim Webster, Jordan Wedlin, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Emma Welch, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Benjamin Welham, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Victoria Wenn, Lauren Wentworth, Joan Wesonga, Kate Wesseldine, Joe West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Kelly Westwood, Sharon Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Andrew White, Ayesha White, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Nikki White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Kelly Whitehorn, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Louiza Whiteley, Sophie Whiteley, Rachael Whitham, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Ashleigh Wignall, Christopher Wignall, Annamaria Wilce, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Ben Wild, Laura Wild, Stephen Wild, Michael Wilde, Laura Wilding, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Anna Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Eleri Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, Heledd Williams, James Williams, Jennie Williams, Jill Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Mandy Williams, Marie Williams, Mark Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachel Williams, Robin Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Steffan Williams, Tamanna Williams, Tania Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Jodie Williamson, Rachel Williamson, Helen Williamson, Elaine Willis, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Jayne Willson, Alison Wilson, Andrea Wilson, Anna Wilson, Antoinette Wilson, Billy Wilson, David Wilson, Imogen Wilson, James Wilson, Karen Wilson, Kate Wilson, Kristy-Ann Wilson, Lucinda Wilson, Mark Wilson, Stephen Wilson, Toni Wilson, John Wilson, Khin Lei Yee Win, Marlar Win, Than Win, Tin Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Stuart Winearl, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Joseph Winterton, Hannah Winwood, Jack Wischhusen, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Tabitha WIshlade, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Chi-Man Wong, Edwin Wong, Jessica S Y Wong, Kit Y Wong, Mei Yin Wong, Nick Wong, Sam Wong, Ting Wong, Aaron B Wongkyezeng, Amanda Wood, Caroline Wood, Dianne Wood, Fiona Wood, Gordon Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Madeleine Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Myles Woodman, Stephen Woodmansey, Charlotte Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Holly Wright, Imogen Wright, Lianne Wright, Rachel Wright, Sarah Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Subie Wurie, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Bingru E Xia, Zhongyang Xia, Effua Yacoba, Santosh Yadav, Masseh Yakubi, May Yan, Yuuki Yanagisawa, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Jessica Ye, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Lam Minh Yen, Alastair Yeoh, Chun Yu Yeung, Peter Yew, Durgesh Yewatkar, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Hartantri Yovita, Chrissie Yu, Jack S J Yuan, Nindya Yufaniaputri, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Mahrukh Zainab, Thornton Zak, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Marcelina Zawadzka, Mohammed Zayed, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Darius Zeinali, Jing Zhang, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eva Zincone, Garikai Zindoga, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Letizia Zitter, Arkadiusz Zmierczak, Garazi Zubikarai, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, and Group, RECOVERY Collaborative
Subjects: Adult, Male, Hypoxia/etiology, SARS-CoV-2, COVID-19, 3rd-DAS, General Medicine, Adrenal Cortex Hormones/therapeutic use, AC, Dexamethasone/therapeutic use, Hospitals, Oxygen, Treatment Outcome, SDG 3 - Good Health and Well-being, MCP, Humans, Female
Abstract: Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation Findings Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). Interpretation In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Funding UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.
Published: 2023
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42. Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial

Author: González-Martín, Antonio, Desauw, Christophe, Heitz, Florian, Cropet, Claire, Gargiulo, Piera, Berger, Regina, Ochi, Hiroyuki, Vergote, Ignace, Colombo, Nicoletta, Mirza, Mansoor R, Tazi, Youssef, Canzler, Ulrich, Zamagni, Claudio, Guerra-Alia, Eva M, Levaché, Charles B, Marmé, Frederik, Bazan, Fernando, de Gregorio, Nikolaus, Dohollou, Nadine, Fasching, Peter A, Scambia, Giovanni, Rubio-Pérez, María J, Milenkova, Tsveta, Costan, Cristina, Pautier, Patricia, Ray-Coquard, Isabelle, PAOLA1/ENGOT-ov25 investigators, Gonzalez-Martin, A, Desauw, C, Heitz, F, Cropet, C, Gargiulo, P, Berger, R, Ochi, H, Vergote, I, Colombo, N, Mirza, M, Tazi, Y, Canzler, U, Zamagni, C, Guerra-Alia, E, Levache, C, Marme, F, Bazan, F, de Gregorio, N, Dohollou, N, Fasching, P, Scambia, G, Rubio-Perez, M, Milenkova, T, Costan, C, Pautier, P, and Ray-Coquard, I
Subjects: Ovarian Neoplasms, Cancer Research, Science & Technology, Antineoplastic Agents, Carcinoma, Ovarian Epithelial, Poly(ADP-ribose) Polymerase Inhibitors, Piperazines, Progression-Free Survival, Bevacizumab, Settore MED/40 - GINECOLOGIA E OSTETRICIA, PARP inhibitor, Olaparib, Antiangiogenic agent, Second progression-free survival, Double-Blind Method, Oncology, Ovarian cancer, Antineoplastic Combined Chemotherapy Protocols, Humans, Phthalazines, Female, Life Sciences & Biomedicine
Abstract: BACKGROUND: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1. METHODS: This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure. RESULTS: After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64-0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64-0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab. CONCLUSION: In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab. ispartof: EUROPEAN JOURNAL OF CANCER vol:174 pages:221-231 ispartof: location:England status: published
Published: 2022
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43. Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure

Author: Matthew T. Scharf, Peng Zhang, Nathan A. Walker, Mariam Mirza, Aesha M. Jobanputra, R. Nisha Aurora, Jag Sunderram, and Shou-En Lu
Subjects: Pulmonary and Respiratory Medicine, Male, Sex Characteristics, Sleep Apnea, Obstructive, Sleepiness, Treatment Outcome, Neurology, Continuous Positive Airway Pressure, Humans, Female, Neurology (clinical), Retrospective Studies
Abstract: Continuous positive airway pressure (CPAP) improves sleepiness in patients with obstructive sleep apnea, but some patients remain sleepy. The objective of this study was to identify determinants that are associated with improvements in self-reported sleepiness in patients with obstructive sleep apnea on CPAP therapy.A retrospective cohort study was performed in a clinic-based population to determine which variables contributed to the improvement in the Epworth Sleepiness Scale (ESS) in patients on CPAP therapy for OSA, stratified by baseline ESS score (11 or ≥ 11). Variables associated with ESS scores normalizing with CPAP were also assessed.Patients with a baseline high ESS score showed greater improvements in the ESS with CPAP. When looking at interactions between baseline ESS classification and changes in ESS, we found that a higher apnea-hypopnea index was only associated with improvement in the ESS among patients with a high baseline ESS. Other assessed factors or covariates were not significantly different. When looking at ESS normalization, we found that female sex and lower body mass index were associated with a lower likelihood of ESS normalization. The difference in the rate of ESS normalization between females and males was higher with more days on CPAP.Of all the assessed factors and covariates, only the apnea-hypopnea index was associated with the change in the ESS differently in patients with a high or normal baseline ESS score. ESS normalization rates were lower in females than in males, and this disparity was amplified by more days on CPAP.Scharf MT, Zhang P, Walker NA, et al. Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure.
Published: 2023

44. Predicting time-to-conversion for dementia of Alzheimer's type using multi-modal deep survival analysis

Author: Mirabnahrazam, Ghazal, Ma, Da, Beaulac, Cédric, Lee, Sieun, Popuri, Karteek, Lee, Hyunwoo, Cao, Jiguo, Galvin, James E, Wang, Lei, Beg, Mirza Faisal, and Initiative, the Alzheimer's Disease Neuroimaging
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Aging, General Neuroscience, Neuroimaging, Magnetic Resonance Imaging, Survival Analysis, Machine Learning (cs.LG), Alzheimer Disease, Disease Progression, Humans, Cognitive Dysfunction, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Abstract: Dementia of Alzheimer's Type (DAT) is a complex disorder influenced by numerous factors, and it is difficult to predict individual progression trajectory from normal or mildly impaired cognition to DAT. An in-depth examination of multiple modalities of data may yield an accurate estimate of time-to-conversion to DAT for preclinical subjects at various stages of disease development. We used a deep-learning model designed for survival analyses to predict subjects' time-to-conversion to DAT using the baseline data of 401 subjects with 63 features from MRI, genetic, and CDC (Cognitive tests, Demographic, and CSF) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our study demonstrated that CDC data outperform genetic or MRI data in predicting DAT time-to-conversion for subjects with Mild Cognitive Impairment (MCI). On the other hand, genetic data provided the most predictive power for subjects with Normal Cognition (NC) at the time of the visit. Furthermore, combining MRI and genetic features improved the time-to-event prediction over using either modality alone. Finally, adding CDC to any combination of features only worked as well as using only the CDC features.
Published: 2023
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45. Racial Disparities in Psychiatric Decisional Capacity Consultations

Author: William S, Garrett, Anita, Verma, Daniel, Thomas, Jacob M, Appel, and Omar, Mirza
Subjects: Hospitalization, Psychiatry and Mental health, Mental Disorders, Humans, Hispanic or Latino, Healthcare Disparities, Referral and Consultation
Abstract: In this study, the authors examined potential disparities and biases in the placement and outcomes of decisional capacity evaluations across races, controlling for patient characteristics.The authors reviewed 181 patient decisional capacity consultations requested for the consultation-liaison psychiatry service at a tertiary care medical center from 2018 to 2019. The racial distribution of patients in these consultations was compared with the racial distribution of hospital inpatient admissions from 2018 to 2019. The authors analyzed patient outcomes by using logistic regression that controlled for race, gender, age, education, primary insurance, type of capacity assessment, and psychiatric diagnosis.Decisional capacity consultations were placed disproportionately for Black (43% of consultations vs. 18% of total admissions) and Hispanic patients (26% of consultations vs. 21% of admissions) compared with White and Asian patients. Among 130 patients with a capacity determination, 95 (53% of total sample) were determined not to have capacity, an outcome that did not differ by race but was more likely to occur among patients diagnosed as having delirium. Sixty-seven patients with no capacity (37% of total sample) experienced a change in treatment, an outcome that was less likely to occur among Hispanic patients in the univariable analysis.Significant racial disparities were observed during the placement of a decisional capacity consultation. These findings reveal the potential biases introduced with both the initial challenge to a patient's capacity and the subsequent outcomes of the consultation. As such, the balance of risk versus benefit or utility of these consultations in certain populations must be carefully considered.
Published: 2023
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46. Individual common variants exert weak effects on the risk for autism spectrum disorders

Author: Anney, Richard, Klei, Lambertus, Pinto, Dalila, Almeida, Joana, Bacchelli, Elena, Baird, Gillian, Bolshakova, Nadia, Bölte, Sven, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Brian, Jessica, Casey, Jillian, Conroy, Judith, Correia, Catarina, Corsello, Christina, Crawford, Emily L, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Fombonne, Eric, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Green, Andrew, Green, Jonathan, Guter, Stephen J, Heron, Elizabeth A, Holt, Richard, Howe, Jennifer L, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Jacob, Suma, Kenny, Graham P, Kim, Cecilia, Kolevzon, Alexander, Kustanovich, Vlad, Lajonchere, Clara M, Lamb, Janine A, Law-Smith, Miriam, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Liu, Xiao-Qing, Lombard, Frances, Lord, Catherine, Lotspeich, Linda, Lund, Sabata C, Magalhaes, Tiago R, Mantoulan, Carine, McDougle, Christopher J, Melhem, Nadine M, Merikangas, Alison, Minshew, Nancy J, Mirza, Ghazala K, Munson, Jeff, Noakes, Carolyn, Nygren, Gudrun, Papanikolaou, Katerina, Pagnamenta, Alistair T, Parrini, Barbara, Paton, Tara, Pickles, Andrew, Posey, David J, Poustka, Fritz, Ragoussis, Jiannis, Regan, Regina, Roberts, Wendy, Roeder, Kathryn, Roge, Bernadette, Rutter, Michael L, Schlitt, Sabine, Shah, Naisha, Sheffield, Val C, Soorya, Latha, Sousa, Inês, Stoppioni, Vera, Sykes, Nuala, Tancredi, Raffaella, Thompson, Ann P, Thomson, Susanne, Tryfon, Ana, Tsiantis, John, Van Engeland, Herman, Vincent, John B, Volkmar, Fred, Vorstman, JAS, Wallace, Simon, Wing, Kirsty, Wittemeyer, Kerstin, Wood, Shawn, Zurawiecki, Danielle, Zwaigenbaum, Lonnie, and Bailey, Anthony J
Subjects: Behavioral and Social Science, Clinical Research, Human Genome, Mental Health, Genetics, Brain Disorders, Pediatric, Intellectual and Developmental Disabilities (IDD), Autism, Prevention, Aetiology, 2.1 Biological and endogenous factors, Alleles, Child, Child Development Disorders, Pervasive, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Language Development, Male, Membrane Proteins, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Risk Factors, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Published: 2012

47. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author: Casey, Jillian P, Magalhaes, Tiago, Conroy, Judith M, Regan, Regina, Shah, Naisha, Anney, Richard, Shields, Denis C, Abrahams, Brett S, Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J, Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Cali, Phil, Correia, Catarina, Corsello, Christina, Coutanche, Marc, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Foley, Suzanne, Fombonne, Eric, Freitag, Christine M, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Green, Jonathan, Guter, Stephen J, Hakonarson, Hakon, Holt, Richard, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M, Kolevzon, Alexander, Lamb, Janine A, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Lord, Catherine, Lund, Sabata C, Maestrini, Elena, Mantoulan, Carine, Marshall, Christian R, McConachie, Helen, McDougle, Christopher J, McGrath, Jane, McMahon, William M, Merikangas, Alison, Miller, Judith, Minopoli, Fiorella, Mirza, Ghazala K, Munson, Jeff, Nelson, Stanley F, Nygren, Gudrun, Oliveira, Guiomar, Pagnamenta, Alistair T, Papanikolaou, Katerina, Parr, Jeremy R, Parrini, Barbara, Pickles, Andrew, Pinto, Dalila, Piven, Joseph, Posey, David J, Poustka, Annemarie, Poustka, Fritz, Ragoussis, Jiannis, Roge, Bernadette, Rutter, Michael L, Sequeira, Ana F, Soorya, Latha, Sousa, Inês, Sykes, Nuala, Stoppioni, Vera, Tancredi, Raffaella, Tauber, Maïté, Thompson, Ann P, Thomson, Susanne, Tsiantis, John, Van Engeland, Herman, Vincent, John B, Volkmar, Fred, Vorstman, Jacob AS, Wallace, Simon, Wang, Kai, Wassink, Thomas H, White, Kathy, and Wing, Kirsty
Subjects: Autism, Genetics, Mental Health, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Biotechnology, Pediatric, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adult, Child, Child Development Disorders, Pervasive, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Homozygote, Humans, Linkage Disequilibrium, Male, Middle Aged, Nuclear Family, Polymorphism, Single Nucleotide, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity
Abstract: Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Published: 2012

48. Gender disparities in brain tumours: A Pakistan brain tumour epidemiology study analysis

Author: Mashal Murad, Shah, Muhammad Usman, Khalid, Mohammad Hamza, Bajwa, Farhan A, Mirza, Saad Bin, Anis, Naveed Zaman, Akhunzada, Altaf Ali, Laghari, Muhammad Faraz, Raghib, Sameen, Siddiqi, Syed Ather, Enam, and Erum, Baig
Subjects: Male, Cross-Sectional Studies, Brain Neoplasms, Meningeal Neoplasms, Humans, Female, Pakistan, General Medicine, Retrospective Studies
Abstract: Objective: To explore the differences in demographic, surgical, and prognostic characteristics between the two genders in patients with brain tumours in Pakistan. Methods: This study was a retrospective cross-sectional analysis of patients with a histopathological brain tumour diagnosis across 32 high-volume hospitals in Pakistan. The study period was from January 1, 2019, to December 31, 2019. There were no restrictions on inclusion apart from time. Results: From 2750 patients enrolled in the study, 1605 (58.4%) were male, and 1142 (41.6%) were female . The median age amongst males was 36 (24-49), while the median age amongst females was 37 (24-48). The ratio of married to unmarried patients was 2.7:1 for females and 1.3:1 for males. Surgical treatment was carried out for 1430 (58.1%) males and 1013 (41.9%) females. The median time to surgery was 25 (4-107) days for males and 31 (5-98) days for females. The greatest disparity in tumour malignancy was in grade IV gliomas. Conclusion: Males generally have a higher incidence of brain tumours in our experience, apart from meningiomas, which favour females. The mortality rate and glioblastoma incidence rate are both higher amongst males. However, post-treatment cure is also witnessed. Sociocultural norms play a prominent role in accessing healthcare. Women are generally at a disadvantage compared to their male counterparts, which may impact reporting of brain tumour cases and treatment outcomes. Keywords: Brain neoplasms, Epidemiology, Gender equity, Retrospective study. Continue....
Published: 2022
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49. Preference Signaling Pilot in the Urology Match: Outcomes and Perceptions

Author: Erica Traxel, Lee Richstone, James Brown, Moben Mirza, Kirsten Greene, and Simone Thavaseelan
Subjects: Surveys and Questionnaires, Urology, Humans, Internship and Residency, United States
Abstract: To assess the perceptions and outcomes of the A preference signaling (PS) pilot implemented by the Society of Academic Urology in the 2021-2022 Urology Match cycle.Five non-weighted signals were provided to each applicant, and signals were delivered to programs by the American Urological Association to provide an applicant-centered formal and equitable process to express genuine interest in residency programs. Applicant and program perception and behavior was assessed through surveys. Signal distribution, mean, range, and interview offer rates for overall, signaled, and non-signaled programs were calculated.In the 2021-2022 Urology Match cycle, 566 applicants completed signaling; 2829 total signals were sent to programs with 97% applicant and 100% program participation. Each program received a mean number of 19 signals (range of 1-62), and 25% of programs received 49% of all signals. The overall interview-offer rate for the cohort was 12.5% (6019 interviews held/47,989 applications received); the signaled interview rate was 51% (1443/2829), and the non-signaled interview rate was 10% (4576/45,160) with an approximate 4-fold increase in rate of interview for signaled programs compared to non-signaled programs. There was moderate to high levels of satisfaction from applicants and programs on the overall process. 48% of programs incorporated PS into initial application review.Preference signaling was demonstrated to be feasible and successful in providing a novel applicant-directed, formal, equitable, and credible structured process for applicants to express genuine interest in programs. Additionally, programs were able to incorporate PS into their interview selection and recruitment process.
Published: 2022
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50. Evaluation of Fluoride Release in Chitosan-Modified Glass Ionomer Cements

Author: Cruz Nishanthine, Revathi Miglani, Indira R, Saravanan Poorni, Manali Ramakrishnan Srinivasan, Ali Robaian, Nassreen Hassan Mohammad Albar, Susen Faisal Rajeh Alhaidary, Sultan Binalrimal, Abdullah Almalki, Thilla Sekar Vinothkumar, Harisha Dewan, Waseem Radwan, Mubashir Baig Mirza, Shilpa Bhandi, and Shankargouda Patil
Subjects: Fluorides, Chitosan, Glass Ionomer Cements, Materials Testing, Humans, General Dentistry
Abstract: This study assessed the influence of chitosan nanoparticles on the fluoride-releasing ability of 4 glass ionomer cement (GIC) through an in vitro analysis.Four types of GIC (type II light cure universal restorative, type II universal restorative, GC Fuji VII, and type IX) were modified with nanochitosan particles; 10% chitosan was added to the glass ionomer liquid. Six specimens for each of the 4 groups were created, using expendable Teflon moulds. Discs of each type of GIC (n = 6) were immersed in deionised water at various time intervals. Electrodes selective for fluoride ions were employed to analyse the amount of released fluoride at 1, 7, 14, 21, and 28 days.Chitosan-modified GICs showed greater fluoride release than conventional GICs at all time points. All samples showed an initial high release of fluoride that tapered off with time. The total amount of fluoride released increased from the 1st day to the 28th day on adding chitosan to all the 4 types of GIC. Amongst those, type IX high-strength posterior extra with chitosan released a considerably higher quantity of fluoride at all time intervals.In all the experimental groups, adding chitosan to the glass ionomer liquid had an accelerating effect on its fluoride-releasing property.
Published: 2022
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