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1. Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry.

Author: Garin, O, Kowalski, C, Zamora, V, Roth, R, Ferrer, M, Breidenbach, C, Pont, A, Belin, T, Elashoff, D, Wilhalme, H, Nguyen, A, Kwan, L, Pearman, E, Bolagani, A, Sampurno, F, Papa, N, Moore, C, Millar, J, Connor, S, Villanti, P, and Litwin, M
Subjects: Health-related quality of life, Patient-reported outcomes, Prostate cancer, Registry, Humans, Male, Brachytherapy, Patient Reported Outcome Measures, Prospective Studies, Prostatectomy, Prostatic Neoplasms, Quality of Life, Registries, Urinary Incontinence, Multicenter Studies as Topic
Abstract: INTRODUCTION: Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. METHODS: We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. RESULTS: The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. CONCLUSIONS: Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.
Published: 2023

2. Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage

Author: Durnford, Andrew J, Akarca, Danyal, Culliford, David, Millar, John, Guniganti, Ridhima, Giordan, Enrico, Brinjikji, Waleed, Chen, Ching-Jen, Abecassis, Isaac Josh, Levitt, Michael, Polifka, Adam J, Derdeyn, Colin P, Samaniego, Edgar A, Kwasnicki, Amanda, Alaraj, Ali, Potgieser, Adriaan RE, Chen, Stephanie, Tada, Yoshiteru, Phelps, Ryan, Abla, Adib, Satomi, Junichiro, Starke, Robert M, van Dijk, J Marc C, Amin-Hanjani, Sepideh, Hayakawa, Minako, Gross, Bradley, Fox, W Christopher, Kim, Louis, Sheehan, Jason, Lanzino, Giuseppe, Kansagra, Akash P, Du, Rose, Lai, Rosalind, Zipfel, Gregory J, Bulters, Diederik O, Piccirillo, Jay F, Raman, Hari, Lipsey, , Kim, Vine, Roanna, Cloft, Harry J, Kallmes, David F, Pollock, Bruce E, Link, Michael J, Patibandla, Mohana Rao, Ding, Dale, Buell, Thomas, Paisan, Gabriella, Meyer, R Michael, Kelly, , Cory, Duffill, Jonathan, Ditchfield, Adam, Macdonald, Jason, Laurent, Dimitri, Hoh, Brian, Smith, Jessica, Lockerman, Ashley, Lunsford, L Dade, Jankowitz, Brian T, Gutierrez, Santiago Ortega, Hasan, David, Roa, Jorge A, Rossen, James, Guerrero, Waldo, McGruder, Allen, Charbel, Fady T, Aletich, Victor A, Rose-Finnell, Linda, Peterson, Eric C, Yavagal, Dileep R, Sur, Samir, Kanematsu, Yasuhisa, Yamamoto, Nobuaki, Kinouchi, Tomoya, Korai, Masaaki, Yamaguchi, Izumi, Yamamoto, Yuki, Winkler, Ethan, Lawton, Michael, Rutkowski, Martin, Sultan, M Ali Aziz, Patel, Nirav, and Frerichs, Kai U
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Kidney Disease, Central Nervous System Vascular Malformations, Cerebral Angiography, Drainage, Embolization, Therapeutic, Humans, Outcome Assessment, Health Care, drainage, fistula, hemorrhage, incidence, natural history, CONDOR Investigators, Cardiorespiratory Medicine and Haematology, Neurosciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract: BackgroundCranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.MethodsPatients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference.ResultsOf 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026).ConclusionsThe risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.
Published: 2022

3. Knowledge and insights from a maturing international clinical quality registry.

Author: Sampurno, Fanny, Kowalski, Christoph, Connor, Sarah E, Nguyen, Anissa V, Acuña, Àngels Pont, Ng, Chi-Fai, Foster, Claire, Feick, Günter, Boronat, Olatz Garin, Dieng, Sebastian, Brglevska, Silvana, Ferrante, Stephanie, Leung, Steven, Villanti, Paul, Moore, Caroline M, Graham, Ian D, Millar, Jeremy L, Litwin, Mark S, and Papa, Nathan
Subjects: Cancer, Health and social care services research, 8.1 Organisation and delivery of services, Benchmarking, Delivery of Health Care, Humans, Male, Registries, international clinical quality registry, process evaluation, collaborative working group, documentation, audit and feedback, shared-learning, Information and Computing Sciences, Engineering, Medical and Health Sciences, Medical Informatics
Abstract: Since 2017, the TrueNTH Global Registry (TNGR) has aimed to drive improvement in patient outcomes for individuals with localized prostate cancer by collating data from healthcare institutions across 13 countries. As TNGR matures, a systematic evaluation of existing processes and documents is necessary to evaluate whether the registry is operating as intended. The main supporting documents: protocol and data dictionary, were comprehensively reviewed in a series of meetings over a 10-month period by an international working group. In parallel, individual consultations with local institutions regarding a benchmarking quality-of-care report were conducted. Four consensus areas for improvement emerged: updating operational definitions, appraisal of the recruitment process, refinement of data elements, and improvement of data quality and reporting. Recommendations presented were drawn from our collective experience and accumulated knowledge in operating an international registry. These can be readily generalized to other health-related reporting programs beyond clinical registries.
Published: 2022

4. mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double‐Blind, Placebo‐Controlled Futility Trial and 1‐Year Biomarker Longitudinal Analysis

Author: Palma, Jose‐Alberto, Martinez, Jose, Vernetti, Patricio Millar, Ma, Thong, Perez, Miguel A, Zhong, Judy, Qian, Yingzhi, Dutta, Suman, Maina, Katherine N, Siddique, Ibrar, Bitan, Gal, Ades‐Aron, Benjamin, Shepherd, Timothy M, Kang, Un J, and Kaufmann, Horacio
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Clinical Research, Neurosciences, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Neurological, Double-Blind Method, Humans, Medical Futility, Multiple System Atrophy, Sirolimus, TOR Serine-Threonine Kinases, Treatment Outcome, alpha-Synuclein, mTOR inhibition, autophagy, neurodegeneration, synuclein, parkinsonism, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: BackgroundMultiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models.ObjectiveTo investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants.MethodsRandomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976).ResultsThe trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression.ConclusionsSirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.
Published: 2022

5. Short-Term Western Diet Intake Promotes IL-23‒Mediated Skin and Joint Inflammation Accompanied by Changes to the Gut Microbiota in Mice

Author: Shi, Zhenrui, Wu, Xuesong, Santos Rocha, Clarissa, Rolston, Matthew, Garcia-Melchor, Emma, Huynh, Mindy, Nguyen, Mimi, Law, Timothy, Haas, Kelly N, Yamada, Daisuke, Millar, Neal L, Wan, Yu-Jui Yvonne, Dandekar, Satya, and Hwang, Samuel T
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Autoimmune Disease, Microbiome, Nutrition, Arthritis, Psoriasis, Aetiology, 2.1 Biological and endogenous factors, Skin, Oral and gastrointestinal, Inflammatory and immune system, Animals, Arthritis, Psoriatic, Diet, Western, Disease Models, Animal, Dysbiosis, Gastrointestinal Microbiome, Humans, Imiquimod, Interleukin-23, Mice, Signal Transduction, Oncology and Carcinogenesis, Dermatology & Venereal Diseases, Clinical sciences
Abstract: We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.
Published: 2021

6. Establishing a global quality of care benchmark report

Author: Sampurno, Fanny, Cally, Justin, Opie, Jacinta L, Kannan, Ashwini, Millar, Jeremy L, Finelli, Antonio, Vickers, Andrew J, Moore, Caroline M, Kowalski, Christoph, Foster, Claire, Barocas, Dan A, Galvin, David, Van Basten, Jean-Paul, Gore, John L, Ferencz, Julia, Lawson, Keith A, Ghani, Khurshid R, Kwan, Lorna, Saarela, Olli, Connor, Sarah E, Dieng, Sebastian, Linsell, Susan, Soeterik, Timo FW, Villanti, Paul, Litwin, Mark S, and Evans, Sue M
Subjects: Health Services and Systems, Health Sciences, Generic health relevance, Benchmarking, Delivery of Health Care, Humans, Male, Quality Indicators, Health Care, Registries, Surveys and Questionnaires, international registry, benchmarking, data display, data science, quality indicators, R Markdown, Information Systems, Library and Information Studies, Medical Informatics, Health services and systems, Applied computing
Abstract: BackgroundThe Movember funded TrueNTH Global Registry (TNGR) aims to improve care by collecting and analysing a consistent dataset to identify variation in disease management, benchmark care delivery in accordance with best practice guidelines and provide this information to those in a position to enact change. We discuss considerations of designing and implementing a quality of care report for TNGR.MethodsEleven working group sessions were held prior to and as reports were being built with representation from clinicians, data managers and investigators contributing to TNGR. The aim of the meetings was to understand current data display approaches, share literature review findings and ideas for innovative approaches. Preferred displays were evaluated with two surveys (survey 1: 5 clinicians and 5 non-clinicians, 83% response rate; survey 2: 17 clinicians and 18 non-clinicians, 93% response rate).ResultsConsensus on dashboard design and three data-display preferences were achieved. The dashboard comprised two performance summary charts; one summarising site's relative quality indicator (QI) performance and another to summarise data quality. Binary outcome QIs were presented as funnel plots. Patient-reported outcome measures of function score and the extent to which men were bothered by their symptoms were presented in bubble plots. Time series graphs were seen as providing important information to supplement funnel and bubble plots. R Markdown was selected as the software program principally because of its excellent analytic and graph display capacity, open source licensing model and the large global community sharing program code enhancements.ConclusionsInternational collaboration in creating and maintaining clinical quality registries has allowed benchmarking of process and outcome measures on a large scale. A registry report system was developed with stakeholder engagement to produce dynamic reports that provide user-specific feedback to 132 participating sites across 13 countries.
Published: 2021

7. Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Responsep53 Pathway SNPs and Mutations Interact to Affect Cancer

Author: Zhang, Ping, Kitchen-Smith, Isaac, Xiong, Lingyun, Stracquadanio, Giovanni, Brown, Katherine, Richter, Philipp H, Wallace, Marsha D, Bond, Elisabeth, Sahgal, Natasha, Moore, Samantha, Nornes, Svanhild, De Val, Sarah, Surakhy, Mirvat, Sims, David, Wang, Xuting, Bell, Douglas A, Zeron-Medina, Jorge, Jiang, Yanyan, Ryan, Anderson J, Selfe, Joanna L, Shipley, Janet, Kar, Siddhartha, Pharoah, Paul D, Loveday, Chey, Jansen, Rick, Grochola, Lukasz F, Palles, Claire, Protheroe, Andrew, Millar, Val, Ebner, Daniel V, Pagadala, Meghana, Blagden, Sarah P, Maughan, Timothy S, Domingo, Enric, Tomlinson, Ian, Turnbull, Clare, Carter, Hannah, and Bond, Gareth L
Subjects: Clinical Research, Cancer, Prevention, Human Genome, Patient Safety, Genetics, Biotechnology, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Animals, Antineoplastic Agents, Biomarkers, Pharmacological, Carcinogenesis, Case-Control Studies, Cell Line, Tumor, Disease Progression, Drug Resistance, Neoplasm, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Mutation, Missense, Neoplasms, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Signal Transduction, Treatment Outcome, Tumor Suppressor Protein p53, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic TP53 mutational status to modify cancer risk, progression, and response to therapy. Focusing on a cancer risk SNP (rs78378222) with a well-documented ability to directly influence p53 activity as well as integration of germline datasets relating to cancer susceptibility with tumor data capturing somatically-acquired genetic variation provided supportive evidence for this hypothesis. Integration of germline and somatic genetic data enabled identification of a novel entry point for therapeutic manipulation of p53 activities. A cluster of cancer risk SNPs resulted in increased expression of prosurvival p53 target gene KITLG and attenuation of p53-mediated responses to genotoxic therapies, which were reversed by pharmacologic inhibition of the prosurvival c-KIT signal. Together, our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel combinatorial therapies. SIGNIFICANCE: These results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and present novel therapeutic targets.
Published: 2021

8. Risk factors for increased COVID-19 case-fatality in the United States: A county-level analysis during the first wave

Author: Millar, Jess A, Dao, Hanh Dung N, Stefopulos, Marianne E, Estevam, Camila G, Fagan-Garcia, Katharine, Taft, Diana H, Park, Christopher, Alruwaily, Amaal, Desai, Angel N, and Majumder, Maimuna S
Subjects: Public Health, Health Sciences, Good Health and Well Being, Age Factors, COVID-19, Cross-Sectional Studies, Female, Humans, Male, Models, Theoretical, Pandemics, Prognosis, Risk Factors, United States, General Science & Technology
Abstract: The ongoing COVID-19 pandemic is causing significant morbidity and mortality across the US. In this ecological study, we identified county-level variables associated with the COVID-19 case-fatality rate (CFR) using publicly available datasets and a negative binomial generalized linear model. Variables associated with decreased CFR included a greater number of hospitals per 10,000 people, banning religious gatherings, a higher percentage of people living in mobile homes, and a higher percentage of uninsured people. Variables associated with increased CFR included a higher percentage of the population over age 65, a higher percentage of Black or African Americans, a higher asthma prevalence, and a greater number of hospitals in a county. By identifying factors that are associated with COVID-19 CFR in US counties, we hope to help officials target public health interventions and healthcare resources to locations that are at increased risk of COVID-19 fatalities.
Published: 2021

9. Frequency of health‐care utilization by adults who use illicit drugs: a systematic review and meta‐analysis

Author: Lewer, Dan, Freer, Joseph, King, Emma, Larney, Sarah, Degenhardt, Louisa, Tweed, Emily J, Hope, Vivian D, Harris, Magdalena, Millar, Tim, Hayward, Andrew, Ciccarone, Dan, and Morley, Katherine I
Subjects: Drug Abuse (NIDA only), Health Services, Emergency Care, Clinical Research, Substance Misuse, Brain Disorders, Methamphetamine, Health and social care services research, 8.1 Organisation and delivery of services, Mental health, Good Health and Well Being, Adult, Amphetamines, Australia, Crack Cocaine, Drug Users, Emergency Service, Hospital, Female, Heroin, Hospitalization, Humans, Illicit Drugs, Male, North America, Patient Acceptance of Health Care, Substance-Related Disorders, Health services, Hospitals, Opiates, Primary Health Care, Stimulants, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse
Abstract: AimsTo summarize evidence on the frequency and predictors of health-care utilization among people who use illicit drugs.DesignSystematic search of MEDLINE, EMBASE and PsychINFO for observational studies reporting health-care utilization published between 1 January 2000 and 3 December 2018. We conducted narrative synthesis and meta-analysis following a registered protocol (identifier: CRD42017076525).Setting and participantsPeople who use heroin, powder cocaine, crack cocaine, methamphetamine, amphetamine, ecstasy/3,4-methylenedioxymethamphetamine (MDMA), cannabis, hallucinogens or novel psychoactive substances; have a diagnosis of 'substance use disorder'; or use drug treatment services.MeasurementsPrimary outcomes were the cumulative incidence (risk) and rate of care episodes in three settings: primary care, hospital admissions (in-patient) and emergency department (ED).FindingsNinety-two studies were included, 84% from North America and Australia. Most studies focused on people using heroin, methamphetamine or crack cocaine, or who had a diagnosis of drug dependence. We were able to conduct a meta-analysis of rates across 25 studies reporting ED episodes and 25 reporting hospital admissions, finding pooled rates of 151 [95% confidence interval (CI) = 114-201] and 41 (95% CI = 30-57) per 100 person-years, respectively; on average 4.8 and 7.1 times more often than the general population. Heterogeneity was very high and was not explained by drugs used, country of study, recruitment setting or demographic characteristics. Predictors of health-care utilization were consistent across studies and included unstable housing, drug injection and mental health problems. Opioid substitution therapy was consistently associated with reduced ED presentation and hospital admission. There was minimal research on health-care utilization by people using ecstasy/MDMA, powder cocaine, hallucinogens or novel psychoactive substances.ConclusionsPeople who use illicit drugs are admitted to emergency department or hospital several times more often than the general population.
Published: 2020

10. Research priorities of women at risk for preterm birth: findings and a call to action.

Author: Franck, Linda S, McLemore, Monica R, Williams, Shanell, Millar, Kathryn, Gordon, Anastasia Y, Williams, Schyneida, Woods, Nakia, Edwards, Lisa, Pacheco, Tania, Padilla, Artie, Nelson, Fanta, and Rand, Larry
Subjects: Humans, Premature Birth, Focus Groups, Obstetrics, Pregnancy, Research, Adult, African Americans, Health Priorities, United States, Female, Health Status Disparities, Community-Based Participatory Research, Health disparities, Lived experience, Patient and public involvement, Pregnancy, preterm birth, Research justice, Research priority setting, Women of color, preterm birth, Obstetrics & Reproductive Medicine, Nursing, Paediatrics and Reproductive Medicine, Public Health and Health Services
Abstract: BACKGROUND:Traditional hierarchical approaches to research give privilege to small groups with decision-making power, without direct input from those with lived experience of illness who bear the burden of disease. A Research Justice framework values the expertise of patients and communities as well as their power in creating knowledge and in decisions about what research is conducted. Preterm birth has persisted at epidemic levels in the United States for decades and disproportionately affects women of color, especially Black women. Women of color have not been included in setting the agenda regarding preterm birth research. METHODS:We used the Research Priorities of Affected Communities protocol to elicit and prioritize potential research questions and topics directly from women of color living in three communities that experience disproportionately high rates of preterm birth. Women participated in two focus group sessions, first describing their healthcare experiences and generating lists of uncertainties about their health and/or healthcare during pregnancy. Women then participated in consensus activities to achieve 'top-priority' research questions and topic lists. The priority research questions and topics produced by each group were examined within and across the three regions for similarities and differences. RESULTS:Fifty-four women participated in seven groups (14 sessions) and generated 375 researchable questions, clustered within 22 topics and four overarching themes: Maternal Health and Care Before, During, and After Pregnancy; Newborn Health and Care of the Preterm Baby; Understanding Stress and Interventions to Prevent or Reduce Stress; and Interpersonal and Structural Health Inequities. The questions and topics represent a wide range of research domains, from basic science, translational, clinical, health and social care delivery to policy and economic research. There were many similarities and some unique differences in the questions, topics and priorities across the regions. CONCLUSIONS:These findings can be used to design and fund research addressing unanswered questions that matter most to women at high risk for preterm birth. Investigators and funders are strongly encouraged to incorporate women at the front lines of the preterm birth epidemic in research design and funding decisions, and more broadly, to advance methods to deepen healthcare research partnerships with affected communities.
Published: 2020

11. A Population-Based Trachoma Prevalence Survey Covering Seven Districts of Sangha and Likouala Departments, Republic of the Congo

Author: Missamou, François, Marlhand, Hemilembolo, Dzabatou-Babeaux, Angelie S Patrick, Sendzi, Samuel, Bernasconi, Jérôme, D’Souza, Susan, Bakhtiari, Ana, Millar, Tom, Willis, Rebecca, Bengraïne, Karim, Resnikoff, Serge, and Solomon, Anthony W
Subjects: Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Clinical Research, Good Health and Well Being, Clean Water and Sanitation, Adolescent, Adult, Aged, Child, Child, Preschool, Congo, Cross-Sectional Studies, Female, Humans, Infant, Male, Middle Aged, Prevalence, Sanitation, Trachoma, Trichiasis, Water Supply, Young Adult, trichiasis, water, sanitation, Global Trachoma Mapping Project, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Epidemiology, Ophthalmology and optometry, Public health
Abstract: PurposeWe set out to estimate the prevalence of trachoma and access to water and sanitation in seven suspected-trachoma-endemic districts of northern Congo, surveyed as a single evaluation unit.MethodsFrom a complete list of rural villages in the seven districts, we systematically selected 22 with probability proportional to village size. In selected villages, we included all households where there were fewer than 25 in total, or used compact segment sampling to select a group of approximately 20 households by random draw. In each selected household, all consenting residents aged ≥1 year were examined by Global Trachoma Mapping Project-certified trachoma graders, and data collected on household-level access to water and sanitation.ResultsIn November and December 2015, 466 households were visited in 22 villages, and 2081 (88%) of 2377 residents of those households were examined. No examined individual had trichiasis. The age-adjusted prevalence of the active trachoma sign trachomatous inflammation-follicular (TF) in 1-9-year-olds was 2.5% (95%CI 0.9-4.5%). Only 39% (95%CI 35-44%) of households had access to an improved source of drinking water. Only 10% (95%CI 7-13%) of households had access to an improved sanitation facility.ConclusionTrachoma is not a public health problem in this part of Congo. Access to water and sanitation is inadequate.
Published: 2018

12. Cohort profile: the TrueNTH Global Registry - an international registry to monitor and improve localised prostate cancer health outcomes.

Author: Evans, Sue M, Millar, Jeremy L, Moore, Caroline M, Lewis, John D, Huland, Hartwig, Sampurno, Fanny, Connor, Sarah E, Villanti, Paul, and Litwin, Mark S
Subjects: Humans, Prostatic Neoplasms, Data Collection, Registries, International Cooperation, Quality Indicators, Health Care, Male, Outcome Assessment, Health Care, international health services, prostate disease, quality in health care, Outcome Assessment, Quality Indicators, Health Care, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract: PurposeGlobally, prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry project was established as an international registry monitoring care provided to men with localised prostate cancer (CaP).ParticipantsSites with existing CaP databases in Movember fundraising countries were invited to participate in the international registry. In total, 25 Local Data Centres (LDCs) representing 113 participating sites across 13 countries have nominated to contribute to the project. It will collect a dataset based on the International Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised CaP.Findings to dateA governance strategy has been developed to oversee registry operation, including transmission of reversibly anonymised data. LDCs are represented on the Project Steering Committee, reporting to an Executive Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have been established. A project was undertaken to compare existing datasets, understand capacity at project commencement (baseline) to collect the ICHOM dataset and assist in determining the final data dictionary. 21/25 LDCs provided data dictionaries for review. Some ICHOM data fields were well collected (diagnosis, treatment start dates) and others poorly collected (complications, comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory fields due to poor capture by most existing registries. Participating sites will transmit data through a web interface biannually to the DCC.Future plansRecruitment to the TrueNTH Global Registry-PCOR project will commence in late 2017 with sites progressively contributing reversibly anonymised data following ethical review in local regions. Researchers will have capacity to source deidentified data after the establishment phase. Quality indicators are to be established through a modified Delphi approach in later 2017, and it is anticipated that reports on performance against quality indicators will be provided to LDCs.
Published: 2017

13. Meeting report: a hard look at the state of enamel research.

Author: Klein, Ophir D, Duverger, Olivier, Shaw, Wendy, Lacruz, Rodrigo S, Joester, Derk, Moradian-Oldak, Janet, Pugach, Megan K, Wright, J Timothy, Millar, Sarah E, Kulkarni, Ashok B, Bartlett, John D, Diekwisch, Thomas Gh, DenBesten, Pamela, and Simmer, James P
Subjects: Cell Line, Stem Cells, Dental Enamel, Animals, Humans, Cell Culture Techniques, Amelogenesis, enamel, mineralized tissue, mineralization, ameloblast, stem cell, Medical Biotechnology, Dentistry
Abstract: The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.
Published: 2017

14. MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.

Author: Lv, Cong, Li, Fengyin, Li, Xiang, Tian, Yuhua, Zhang, Yue, Sheng, Xiaole, Song, Yongli, Meng, Qingyong, Yuan, Shukai, Luan, Liming, Andl, Thomas, Feng, Xu, Jiao, Baowei, Xu, Mingang, Plikus, Maksim V, Dai, Xing, Lengner, Christopher, Cui, Wei, Ren, Fazheng, Shuai, Jianwei, Millar, Sarah E, and Yu, Zhengquan
Subjects: Mammary Glands, Human, Cell Line, Tumor, Stem Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Mice, Breast Neoplasms, NF-kappa B, MicroRNAs, Cell Proliferation, Down-Regulation, Gene Expression Regulation, Neoplastic, Female, Wnt Proteins, beta Catenin, Neoplastic Stem Cells, Wnt Signaling Pathway, Cell Self Renewal, Stem Cell Research - Nonembryonic - Human, Breast Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Cancer, Biotechnology, Genetics, 2.1 Biological and endogenous factors, Mammary Glands, Human, Cell Line, Tumor, Inbred C57BL, Transgenic, Gene Expression Regulation, Neoplastic
Abstract: MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-κB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFβ and Wnt/β-catenin. Particularly, it activates Wnt/β-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.
Published: 2017

15. Guidelines for Genome-Scale Analysis of Biological Rhythms

Author: Hughes, Michael E, Abruzzi, Katherine C, Allada, Ravi, Anafi, Ron, Arpat, Alaaddin Bulak, Asher, Gad, Baldi, Pierre, de Bekker, Charissa, Bell-Pedersen, Deborah, Blau, Justin, Brown, Steve, Ceriani, M Fernanda, Chen, Zheng, Chiu, Joanna C, Cox, Juergen, Crowell, Alexander M, DeBruyne, Jason P, Dijk, Derk-Jan, DiTacchio, Luciano, Doyle, Francis J, Duffield, Giles E, Dunlap, Jay C, Eckel-Mahan, Kristin, Esser, Karyn A, FitzGerald, Garret A, Forger, Daniel B, Francey, Lauren J, Fu, Ying-Hui, Gachon, Frédéric, Gatfield, David, de Goede, Paul, Golden, Susan S, Green, Carla, Harer, John, Harmer, Stacey, Haspel, Jeff, Hastings, Michael H, Herzel, Hanspeter, Herzog, Erik D, Hoffmann, Christy, Hong, Christian, Hughey, Jacob J, Hurley, Jennifer M, de la Iglesia, Horacio O, Johnson, Carl, Kay, Steve A, Koike, Nobuya, Kornacker, Karl, Kramer, Achim, Lamia, Katja, Leise, Tanya, Lewis, Scott A, Li, Jiajia, Li, Xiaodong, Liu, Andrew C, Loros, Jennifer J, Martino, Tami A, Menet, Jerome S, Merrow, Martha, Millar, Andrew J, Mockler, Todd, Naef, Felix, Nagoshi, Emi, Nitabach, Michael N, Olmedo, Maria, Nusinow, Dmitri A, Ptáček, Louis J, Rand, David, Reddy, Akhilesh B, Robles, Maria S, Roenneberg, Till, Rosbash, Michael, Ruben, Marc D, Rund, Samuel SC, Sancar, Aziz, Sassone-Corsi, Paolo, Sehgal, Amita, Sherrill-Mix, Scott, Skene, Debra J, Storch, Kai-Florian, Takahashi, Joseph S, Ueda, Hiroki R, Wang, Han, Weitz, Charles, Westermark, Pål O, Wijnen, Herman, Xu, Ying, Wu, Gang, Yoo, Seung-Hee, Young, Michael, Zhang, Eric Erquan, Zielinski, Tomasz, and Hogenesch, John B
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Human Genome, Networking and Information Technology R&D (NITRD), Genetics, Generic health relevance, Biostatistics, Circadian Rhythm, Computational Biology, Genome, Genomics, Humans, Metabolomics, Proteomics, Software, Statistics as Topic, Systems Biology, circadian rhythms, diurnal rhythms, computational biology, functional genomics, systems biology, guidelines, biostatistics, RNA-seq, ChIP-seq, proteomics, metabolomics, Physiology, Neurosciences, Medical Physiology, Neurology & Neurosurgery, Zoology, Biological psychology
Abstract: Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding "big data" that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them.
Published: 2017

16. A DEAD-box protein acts through RNA to promote HIV-1 Rev-RRE assembly

Author: Lamichhane, Rajan, Hammond, John A, Pauszek, Raymond F, Anderson, Rae M, Pedron, Ingemar, van der Schans, Edwin, Williamson, James R, and Millar, David P
Subjects: Biological Sciences, Bioinformatics and Computational Biology, HIV/AIDS, Genetics, Binding Sites, Biological Transport, Carbocyanines, DEAD-box RNA Helicases, Fluorescence Resonance Energy Transfer, Fluorescent Dyes, Gene Expression, Genes, env, HIV-1, Host-Pathogen Interactions, Humans, Nucleic Acid Conformation, Protein Binding, RNA, Messenger, RNA, Viral, Recombinant Fusion Proteins, Rhodamines, Single Molecule Imaging, Staining and Labeling, Sulfonic Acids, Virus Assembly, Environmental Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract: The HIV-1 Rev protein activates nuclear export of unspliced and partially spliced viral RNA transcripts, which encode the viral genome and the genes encoding viral structural proteins, by binding to and oligomerizing on the Rev Response Element (RRE). The human DEAD-box protein 1 (DDX1) enhances the RNA export activity of Rev through an unknown mechanism. Using a single-molecule assembly assay and various DDX1 mutants, we show that DDX1 acts through the RRE RNA to specifically accelerate the nucleation step of the Rev-RRE assembly process. Single-molecule Förster resonance energy transfer (smFRET) experiments using donor-labeled Rev and acceptor-labeled DDX1 show that both proteins can associate with a single RRE molecule. However, simultaneous interaction is only observed in a subset of binding events and does not explain the extent to which DDX1 promotes the nucleation step of Rev-RRE assembly. Together, these results are consistent with a model wherein DDX1 acts as an RNA chaperone, remodeling the RRE into a conformation that is pre-organized to bind the first Rev monomer, thereby promoting the overall Rev-RRE assembly process.
Published: 2017

17. Regeneration of fat cells from myofibroblasts during wound healing

Author: Plikus, Maksim V, Guerrero-Juarez, Christian F, Ito, Mayumi, Li, Yun Rose, Dedhia, Priya H, Zheng, Ying, Shao, Mengle, Gay, Denise L, Ramos, Raul, Hsi, Tsai-Ching, Oh, Ji Won, Wang, Xiaojie, Ramirez, Amanda, Konopelski, Sara E, Elzein, Arijh, Wang, Anne, Supapannachart, Rarinthip June, Lee, Hye-Lim, Lim, Chae Ho, Nace, Arben, Guo, Amy, Treffeisen, Elsa, Andl, Thomas, Ramirez, Ricardo N, Murad, Rabi, Offermanns, Stefan, Metzger, Daniel, Chambon, Pierre, Widgerow, Alan D, Tuan, Tai-Lan, Mortazavi, Ali, Gupta, Rana K, Hamilton, Bruce A, Millar, Sarah E, Seale, Patrick, Pear, Warren S, Lazar, Mitchell A, and Cotsarelis, George
Subjects: Stem Cell Research, Regenerative Medicine, 1.1 Normal biological development and functioning, Underpinning research, Adipocytes, Animals, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Bone Morphogenetic Proteins, Cells, Cultured, Cellular Reprogramming, Cicatrix, DNA-Binding Proteins, Fibroblasts, Hair Follicle, Humans, Mice, Mice, Inbred C57BL, Myofibroblasts, Recombinant Proteins, Regeneration, Signal Transduction, Transcription Factors, Wound Healing, General Science & Technology
Abstract: Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.
Published: 2017

18. Dynamic conformational changes in the rhesus TRIM5α dimer dictate the potency of HIV-1 restriction

Author: Lamichhane, Rajan, Mukherjee, Santanu, Smolin, Nikolai, Pauszek, Raymond F, Bradley, Margret, Sastri, Jaya, Robia, Seth L, Millar, David, and Campbell, Edward M
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, HIV/AIDS, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Dimerization, Disease Models, Animal, HIV Infections, HIV-1, Humans, Macaca mulatta, Mutation, Protein Conformation, Single molecule FRET, TRIM5alpha, Molecular dynamics simulation, smFRET, Restriction factor, Coiled coil, Dimer, Tripartite Motif, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract: The TRIM5α protein from rhesus macaques (rhTRIM5α) mediates a potent inhibition of HIV-1 infection via a mechanism that involves the abortive disassembly of the viral core. We have demonstrated that alpha-helical elements within the Linker 2 (L2) region, which lies between the SPRY domain and the Coiled-Coil domain, influence the potency of restriction. Here, we utilize single-molecule FRET analysis to reveal that the L2 region of the TRIM5α dimer undergoes dynamic conformational changes, which results in the displacement of L2 regions by 25 angstroms relative to each other. Analysis of restriction enhancing or abrogating mutations in the L2 region reveal that restriction defective mutants are unable to undergo dynamic conformational changes and do not assume compact, alpha-helical conformations in the L2 region. These data suggest a model in which conformational changes in the L2 region mediate displacement of CA bound SPRY domains to induce the destabilization of assembled capsid during restriction.
Published: 2017

19. 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, 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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 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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 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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 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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, 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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, 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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 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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, Anna Hewetson, Sue Hewins, Nicola Hewitson, Claire Hewitt, Davina Hewitt, Richard Hewitt, Samuel Hey, Robert S Heyderman, Mathis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, John Hickey, Naomi Hickey, Peter Hickey, Nicky Hickman, Alex Hicks, Jenny Hicks, Scott R Hicks, Phan Thi Thu Hien, Daniel Higbee, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Lisa Hill, Lucy Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Catherine Hillman-Cooper, Jon Hilton, Zoe Hilton, Sarah Hinch, Andrew Hindle, Esther Hindley, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Claire Hirst, Lindsay Hirst, Jemma Hives, Htet M Hlaing, Benson Ho, David K K Ho, Rosemary Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Christopher Hodge, Simon Hodge, Lesley Hodgen, George Hodgetts, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, 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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, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Megan Hume, Charlotte Humphrey, Alasdair Humphries, Amy Humphries, Joanne Humphries, Charlotte Hunt, Fiona Hunt, Jane Hunt, Jonquil Hunt, Kristen Hunt, Luke Hunt, Molly Hunt, Sophie Hunt, Alexandra Hunter, Catherine Hunter, Ewan Hunter, Karl Hunter, Neil Hunter, Ross Hunter, Sophie Hunter, George Huntington, Fuad Huq, Elizabeth Hurditch, Judith Hurdman, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Afreen Hussain, Chreif Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Mohammed Hussain, Muhammad Hussain, Reda Hussain, Rizwana Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Samahir F E M Hussein, Ziad Hussein, Rebecca Hussey, Adiel Haqiq Hussien, Anja Hutchinson, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Nguyen Quang Huy, Thuong Huyen, Tran Bang Huyen, Nguyen Thi Huyen 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Julie Jones, Kate E Jones, Kimberly Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nancy Jones, Nicola Jones, Olivia Jones, Paul Jones, Philip H Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Susan Jones, Taya Jones, Thomas Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Michele Jordan, Sarah Jordan, Abi Jose, Litty Jose, Louise Jose, Sanal Jose, Anna Joseph, Gigee Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Tushar Joshi, Benz Josiah, Lijo Joy, Tiffany Joyce, Hong Ju, Adriel Ju Wen Kwek, Andrew Judd, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Nikhil Kadam, Nicole Kader, Ajai Kailey, Matthew Kain, Gail Kakoullis, Azad Kala Bhushan, Richard J K Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Thomas Kalmus Eliasz, Seika Kalsoom, Elisa Kam, 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Robert Laing, Inez Laing-Faiers, Emily Laity, Katharine Lake, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Classy Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Oscar Lambert, Pauline Lambert, Claudia Lameirinhas, Mohammed K G Lami, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Ivone Lancona-Malcolm, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emma Langridge, Emily Langthorne, Helen Langton, Beatriz Lara, Taiya Large, Lawrencia Naadu Lartey, Samuel Lassa, Anna Last, Scott Latham, Victoria Latham, Afzal Latheef, Larissa Latif, Nang Latt, Carmen Lau, Dawn Lau, Eva Lau, Gonzalez G Laura, Myra Laurenson, Eloise Lavington, Hou Law, Jessica Law, June Law, Kar Y Law, Penny Law, Richard Law, Laura Lawless, Chris Lawrence, Emma Lawrence, Geoffrey Lawrence, Holly M Lawrence, Neil Lawrence, Ryan Lawrie, Louise Lawson, Natalie Lawson, Rod Lawson, Michael Lay, Stephen Laybourne, Christine Laycock, Reina Layug, Maria Lazo, Thi Thao Le, Vietland Le, Amelia Lea, William Lea, Louisa E Leach, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Ruth Leary, Sandra Leason, Marie A Ledingham, Caroline Lee, Emma Lee, Hannah Lee, Irish Lee, Joshua Lee, Judith Lee, Sam Lee, Shannon Lee, Shi Han Lee, Simon Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Robyn Lee, Diana Lees, Jennifer Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, David Leitch, Nicky Leitch, Eleni Lekoudis, Petula Lemessy, Nicholas Lemoine, Rebecca Lenagh, Katy Leng, Katrina Lennon, Liz Lennon, Beth Leonard, Kelly Leonard, Wen Leong, Nicky Leopold, Oskar Lepiarczyk, Isla Leslie, Eva Noviani Lestari, Eleni Lester, Emma Levell, Chris Levett, Anastasia Levynska, Alice Lewin, Alison Lewis, Christopher Lewis, David Lewis, Dee Lewis, Heather Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Mandy Lewis, Marissa Lewis, Nicolas Lewis, Robert Lewis, Catherine Lewis-Clarke, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Angela Liao, Victoria Licence, David Lieberman, Susan Liebeschuetz, Teresa Light, Nicky Lightfoot, Patrick Lillie, Ashling Lillis, Ben Lim, Carys Lim, Ee T Lim, Ivy Lim, Terence Lim, Wei Shen Lim, Wilson Lim, James Limb, Dipraj Limbu, Usha Limbu, Christian Linares, Dermot Linden, Gabriella Lindergard, Kate Lindley, Charlotte Lindsay, Emily Lindsay, Max Lindsay, Helen Lindsay- Clarke, Mirella Ling, Claire Lingam, Linette Linkson, Thinzar Linn, Mike Linney, Conrad Lippold, George Lipscomb, Karen Lipscomb, Laura Lipskis, Ana Lisboa, Evangeline Lister, Jeff Little, Sam Little, Lucy Littlejohn, Sky Liu, Xuedi Liu, Daniel K Llanera, Rhiannon Llewellyn, Martin Llewelyn, Adam Lloyd, Aimee Lloyd, Arwel Lloyd, Oliver Lloyd, Richard Lloyd, Su Lo, David Loader, Caroline Loan, Livia Lobosco, Lydianne Lock, Sara Lock, Stephen Lock, Angela Locke, Jacqueline Locke, Thomas Locke, Teresa Lockett, Jeorghino Lodge, Krishan 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Katie Slack, Heather Slade, Mark Slade, Lynda Slater, Nicola Slawson, Rachel Slingsby, Andrew Sloan, Brendan Sloan, Derek Sloan, Geraldine Sloane, Malgorzata Slowinska, Benjamin Small, Ellen Small, Samuel Small, Adam Smallridge, Dawn Smalls, Karen Denise Smallshaw, Andy Smallwood, Brittany Smart, Lynne Smart, Justyna Smeaton, Carien Smit, Aileen Smith, Alex Smith, Amanda Smith, Amy Smith, Andrew Smith, Catherine Smith, Chris Smith, Christopher Smith, Coral Smith, Debra Smith, Dominic Smith, Eleanor Smith, Harriet Smith, Hazel Smith, Helen Smith, Jacky Smith, Jessica Smith, Kate Smith, Kerry Smith, Lara Smith, Linda Smith, Lisa Smith, Loren Smith, Maria Smith, Mark Smith, Martha A Smith, Mel Smith, Nicholas Smith, Oliver Smith, Philippa Smith, Rachel Smith, Rebecca Smith, Rheanna Smith, Richard Smith, Sally Smith, Samantha Smith, Stacey Smith, Stephanie Smith, Susan Smith, Tracy Smith, Victoria Smith, Imogen Smith, John Smith, Sue Smolen, Sara Smuts, Naoise Smyth, Annette Snell, David 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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

20. Beyond too little, too late and too much, too soon: a pathway towards evidence-based, respectful maternity care worldwide

Author: Miller, Suellen, Abalos, Edgardo, Chamillard, Monica, Ciapponi, Agustin, Colaci, Daniela, Comandé, Daniel, Diaz, Virginia, Geller, Stacie, Hanson, Claudia, Langer, Ana, Manuelli, Victoria, Millar, Kathryn, Morhason-Bello, Imran, Castro, Cynthia Pileggi, Pileggi, Vicky Nogueira, Robinson, Nuriya, Skaer, Michelle, Souza, João Paulo, Vogel, Joshua P, and Althabe, Fernando
Subjects: Biomedical and Clinical Sciences, Midwifery, Public Health, Health Sciences, Reproductive Medicine, Pediatric, Health Services, Clinical Research, Health and social care services research, 7.3 Management and decision making, Management of diseases and conditions, 8.1 Organisation and delivery of services, Reproductive health and childbirth, Generic health relevance, Good Health and Well Being, Evidence-Based Medicine, Female, Global Health, Health Status Disparities, Humans, Maternal Health Services, Maternal Mortality, Practice Guidelines as Topic, Pregnancy, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract: On the continuum of maternal health care, two extreme situations exist: too little, too late (TLTL) and too much, too soon (TMTS). TLTL describes care with inadequate resources, below evidence-based standards, or care withheld or unavailable until too late to help. TLTL is an underlying problem associated with high maternal mortality and morbidity. TMTS describes the routine over-medicalisation of normal pregnancy and birth. TMTS includes unnecessary use of non-evidence-based interventions, as well as use of interventions that can be life saving when used appropriately, but harmful when applied routinely or overused. As facility births increase, so does the recognition that TMTS causes harm and increases health costs, and often concentrates disrespect and abuse. Although TMTS is typically ascribed to high-income countries and TLTL to low-income and middle-income ones, social and health inequities mean these extremes coexist in many countries. A global approach to quality and equitable maternal health, supporting the implementation of respectful, evidence-based care for all, is urgently needed. We present a systematic review of evidence-based clinical practice guidelines for routine antenatal, intrapartum, and postnatal care, categorising them as recommended, recommended only for clinical indications, and not recommended. We also present prevalence data from middle-income countries for specific clinical practices, which demonstrate TLTL and increasing TMTS. Health-care providers and health systems need to ensure that all women receive high-quality, evidence-based, equitable and respectful care. The right amount of care needs to be offered at the right time, and delivered in a manner that respects, protects, and promotes human rights.
Published: 2016

21. CD133 Expression Correlates with Membrane Beta-Catenin and E-Cadherin Loss from Human Hair Follicle Placodes during Morphogenesis

Author: Gay, Denise L, Yang, Chao-Chun, Plikus, Maksim V, Ito, Mayumi, Rivera, Charlotte, Treffeisen, Elsa, Doherty, Laura, Spata, Michelle, Millar, Sarah E, and Cotsarelis, George
Subjects: Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, AC133 Antigen, Animals, Antigens, CD, Cadherins, Cell Differentiation, Cell Proliferation, Epithelial-Mesenchymal Transition, Gene Knock-In Techniques, Glycoproteins, Hair Follicle, Humans, Membrane Proteins, Mice, Mutant Strains, Morphogenesis, Peptides, Scalp, Transcriptome, Wnt Signaling Pathway, beta Catenin, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases
Abstract: Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode "budding" is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions (AJs) is clearly required for budding. Snail-mediated downregulation of AJ component E-cadherin is important for placode budding in mice. Beta-catenin, another AJ component, has been more difficult to study owing to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.
Published: 2015

22. Starvation ketoacidosis and refeeding syndrome

Author: Angela Heulwen Boal, Maurizio Panarelli, and Caroline Millar
Subjects: Acid-Base Equilibrium, Male, Starvation, Water-Electrolyte Imbalance, Humans, General Medicine, Ketosis, Refeeding Syndrome, Acidosis, Aged
Abstract: Starvation ketoacidosis (SKA) is a rarer cause of ketoacidosis. Most patients will only have a mild acidosis, but if exacerbated by stress can result in a severe acidosis. We describe a 66-year-old man admitted with reduced consciousness and found to have a severe metabolic acidosis with raised anion gap. His body mass index (BMI) was noted to be within the healthy range at 23 kg/m2; however, it was last documented 1 year previously at 28 kg/m2 with no clear timeframe of weight loss. While his acidosis improved with intravenous fluids, he subsequently developed severe electrolyte imbalance consistent with refeeding during his admission. Awareness of SKA as a cause for high anion gap metabolic acidosis is important and knowledge of management including intravenous fluids, thiamine, dietetic input and electrolyte replacement is vital.
Published: 2023

23. Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis

Author: Zhang, Yaqing, Morris, John P, Yan, Wei, Schofield, Heather K, Gurney, Austin, Simeone, Diane M, Millar, Sarah E, Hoey, Timothy, Hebrok, Matthias, and di Magliano, Marina Pasca
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Stem Cell Research, Rare Diseases, Pancreatic Cancer, Stem Cell Research - Nonembryonic - Non-Human, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Apoptosis, Blotting, Western, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Transformation, Neoplastic, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Pancreatic Neoplasms, Real-Time Polymerase Chain Reaction, Wnt Signaling Pathway, beta Catenin, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract: Wnt ligand expression and activation of the Wnt/β-catenin pathway have been associated with pancreatic ductal adenocarcinoma, but whether Wnt activity is required for the development of pancreatic cancer has remained unclear. Here, we report the results of three different approaches to inhibit the Wnt/β-catenin pathway in a established transgenic mouse model of pancreatic cancer. First, we found that β-catenin null cells were incapable of undergoing acinar to ductal metaplasia, a process associated with development of premalignant pancreatic intraepithelial neoplasia lesions. Second, we addressed the specific role of ligand-mediated Wnt signaling through inducible expression of Dkk1, an endogenous secreted inhibitor of the canonical Wnt pathway. Finally, we targeted the Wnt pathway with OMP-18R5, a therapeutic antibody that interacts with multiple Frizzled receptors. Together, these approaches showed that ligand-mediated activation of the Wnt/β-catenin pathway is required to initiate pancreatic cancer. Moreover, they establish that Wnt signaling is also critical for progression of pancreatic cancer, a finding with potential therapeutic implications.
Published: 2013

24. Evaluation of Clinical Metrics for Identifying Defective Physiologic Responses to Hypoglycemia in Long-Standing Type 1 Diabetes

Author: Anneliese J. Flatt, Elizabeth Chen, Amy J. Peleckis, Cornelia Dalton-Bakes, Huong-Lan Nguyen, Heather W. Collins, John S. Millar, Robert J. Gallop, and Michael R. Rickels
Subjects: Adult, Blood Glucose, Endocrinology, Diabetes and Metabolism, Blood Glucose Self-Monitoring, Insulins, Middle Aged, Hypoglycemia, Medical Laboratory Technology, Benchmarking, Endocrinology, Diabetes Mellitus, Type 1, Glucose, Humans, Hypoglycemic Agents, Insulin
Abstract: Repeated hypoglycemia exposure leads to impaired awareness of hypoglycemia (IAH) and the development of defective counterregulatory responses. To date, only pancreas or islet transplantation has demonstrated normalization of hypoglycemia awareness and the endogenous glucose production (EGP) response to defend against insulin-induced hypoglycemia in long-standing type 1 diabetes (T1D). This study aims to validate clinical metrics of IAH (Clarke score), hypoglycemia severity (HYPO score), glycemic lability (lability index), and continuous glucose monitoring (CGM) as predictors of absent autonomic symptom (AS) recognition and defective glucose counterregulation during insulin-induced hypoglycemia, thus enabling early identification of individuals with compromised physiologic defense against clinically significant hypoglycemia. Forty-three subjects with mean ± standard deviation age 43 ± 13 years and T1D duration 28 ± 13 years, including 32 with IAH and 11 with hypoglycemia awareness (Aware), and 12 nondiabetic control subjects, underwent single-blinded randomized-paired hyperinsulinemic-euglycemic and hypoglycemic clamp experiments. Receiver operating characteristic (ROC) curves and sensitivity analyses were performed to assess metric prediction of absent AS recognition and defective EGP responses to hypoglycemia. Clarke score and CGM measures of hypoglycemia exposure demonstrated good ability to predict absent AS recognition (area under the curve ≥0.80). A composite threshold of IAH-Clarke ≥4 with ROC curve-derived thresholds for CGM measures of hypoglycemia exposure showed high specificity and predictive value in identifying an absent AS response during the hypoglycemic clamp. Metrics demonstrated poor ability to predict defective glucose counterregulation by the EGP response, which was impaired even in the Aware group. Screening for IAH alongside assessment of CGM data can increase the specificity for identifying individuals with absent hypoglycemia symptom recognition who may benefit from further intervention.
Published: 2023

25. Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype

Author: Agata Oliwa, Shuko Joseph, Eoghan Millar, Iain Horrocks, Dawn Penman, Julia Baptista, Thomas Cullup, Panayiotis Constantinou, Anne-Marie Heuchan, Ruth Hamilton, and Cheryl Longman
Subjects: Muscular Atrophy, Spinal, Phenotype, Lower Extremity, Neurology, Pregnancy, Humans, Evoked Potentials, Visual, Female, Neurology (clinical), Spinal Muscular Atrophies of Childhood, Microtubule-Associated Proteins, Cataract
Abstract: This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials (VEPs) and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataract, abnormal electroretinograms and VEPs are novel features of SMA-LED2.
Published: 2022

26. Attitudes & practices surrounding pregnancy post heart transplant among pediatric providers

Author: Megan M. Collins, Zhining Ou, Morgan M. Millar, Michelle M. Kittleson, Lindsay J. May, Michelle S. Ploutz, Kimberly M. Molina, Katherine G. Hayes, and Ashwin K. Lal
Subjects: Adult, Pulmonary and Respiratory Medicine, Transplantation, United States, Attitude, Pregnancy, Surveys and Questionnaires, Humans, Heart Transplantation, Female, Surgery, Child, Cardiology and Cardiovascular Medicine, Lung Transplantation
Abstract: Many pediatric heart transplant (HT) recipients reach adulthood and may be interested in family planning; there is little data regarding safety of pregnancy post HT and clinicians' opinions differ. Pediatric HT clinicians are instrumental in early counseling. Thus, a better understanding of pediatric HT clinicians' practices regarding family planning and how well aligned these practices are with adult transplant centers is essential.We conducted a confidential, web-based survey of pediatric HT clinicians in fall 2021. We summarized and compared answers using Fisher's exact test.The survey was sent to 53 United States-based HT directors and to the International Society for Heart and Lung Transplantation and Pediatric Heart Transplant Society list serves. There were 69 respondents. The majority (77%) of respondents felt pregnancy was feasible in selected or all female HT recipients. Ten respondents reported that their institution had an established policy regarding pregnancy post HT. A majority (77%) of HT clinicians would either use a shared care model or recommend transition to their adult institution if pregnancy occurred, though 74% of respondents were either unaware of their corresponding adult institution's policy (62%) or had a counterpart adult program with a policy against pregnancy post HT (12%).While many clinicians feel pregnancy is feasible in pediatric HT recipients, there remains significant practice variation. Few pediatric programs have a policy regarding pregnancy post HT. Future efforts to provide consistent messaging between adult and pediatric HT programs regarding the feasibility and care of post HT pregnancy are warranted.
Published: 2022

27. Influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity in healthy adults

Author: Mark B. Badrov, Daniel A. Keir, Catherine F. Notarius, Emma O’Donnell, Philip J. Millar, Derek S. Kimmerly, J. Kevin Shoemaker, and John S. Floras
Subjects: Adult, Male, Oxygen, Sympathetic Nervous System, Physiology, Physiology (medical), Humans, Female, Blood Pressure, Muscle, Skeletal, Cardiology and Cardiovascular Medicine, Exercise
Abstract: Our data reveal for the first time that associations between aerobic fitness and resting muscle sympathetic nerve activity are sex and age specific; inverse relationships are evident in younger males (
Published: 2022

28. Assessing functional sympatholysis during rhythmic handgrip exercise using Doppler ultrasound and near-infrared spectroscopy: sex differences and test-retest reliability

Author: André L. Teixeira, Matthew Garland, Jordan B. Lee, Massimo Nardone, and Philip J. Millar
Subjects: Adult, Male, Sex Characteristics, Spectroscopy, Near-Infrared, Hand Strength, Physiology, Reproducibility of Results, Ultrasonography, Doppler, Forearm, Oxygen Consumption, Vasoconstriction, Regional Blood Flow, Physiology (medical), Sympatholytics, Humans, Female, Muscle, Skeletal, Muscle Contraction
Abstract: The effects of sympathetic activity on vasoconstriction are dampened in active skeletal muscle during exercise, a phenomenon termed functional sympatholysis. Limited work has examined the influence of sex on the magnitude of sympatholysis or the test-retest reliability of measurements. In 16 women and 15 men, forearm blood flow (FBF; Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy, NIRS), and beat-to-beat mean arterial pressure (MAP; photoplethysmography) were measured during lower-body negative pressure (LBNP; −20 mmHg) at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction). Measures were taken twice within the same visit (separated by 15 min) and repeated on a second visit. Forearm vascular conductance (FVC) was calculated as FBF/MAP. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes between handgrip and rest. LBNP decreased FBF (Δ−45 ± 15%), FVC (Δ−45 ± 16%), and muscle oxygenation (Δ−14 ± 11%); however, these responses were attenuated when LBNP was applied during rhythmic handgrip exercise (Δ−7 ± 9%, Δ−9 ± 10%, and Δ−6 ± 9%, respectively). The magnitude of sympatholysis was not different between men and women (FBF: 40 ± 16% vs. 35 ± 9%, P = 0.37; FVC: 38 ± 16% vs. 35 ± 11%, P = 0.53; muscle oxygenation: 5 ± 9% vs. 11 ± 10%, P = 0.11). Furthermore, sympatholysis measurements demonstrated good to excellent intraday (intraclass-correlation coefficients; ICC ≥ 0.85) and interday (ICC ≥ 0.72) test-retest reliability (all P ≤ 0.01) in both sexes. The coefficients of variation were larger with NIRS (68–91%) than with Doppler ultrasound (16%−22%) assessments of functional sympatholysis. Collectively, these findings demonstrate that assessments of functional sympatholysis are not impacted by biological sex and that Doppler ultrasound-derived measures of sympatholysis have better within-subject reliability than NIRS-derived measures in young healthy adults.
Published: 2022

29. Rapid implementation of an integrated large-scale HIV counseling and testing, malaria, and diarrhea prevention campaign in rural Kenya.

Author: Lugada, Eric, Millar, Debra, Haskew, John, Grabowsky, Mark, Garg, Navneet, Vestergaard, Mikkel, Kahn, James G, Muraguri, Nicholas, and Mermin, Jonathan
Subjects: Humans, HIV Infections, Malaria, Diarrhea, Condoms, Counseling, Adolescent, Adult, Middle Aged, Rural Population, Health Promotion, Kenya, Female, Male, Young Adult, Public-Private Sector Partnerships, General Science & Technology
Abstract: BackgroundIntegrated disease prevention in low resource settings can increase coverage, equity and efficiency in controlling high burden infectious diseases. A public-private partnership with the Ministry of Health, CDC, Vestergaard Frandsen and CHF International implemented a one-week integrated multi-disease prevention campaign.MethodResidents of Lurambi, Western Kenya were eligible for participation. The aim was to offer services to at least 80% of those aged 15-49. 31 temporary sites in strategically dispersed locations offered: HIV counseling and testing, 60 male condoms, an insecticide-treated bednet, a household water filter for women or an individual filter for men, and for those testing positive, a 3-month supply of cotrimoxazole and referral for follow-up care and treatment.FindingsOver 7 days, 47,311 people attended the campaign with a 96% uptake of the multi-disease preventive package. Of these, 99.7% were tested for HIV (87% in the target 15-49 age group); 80% had previously never tested. 4% of those tested were positive, 61% were women (5% of women and 3% of men), 6% had median CD4 counts of 541 cell/µL (IQR; 356, 754). 386 certified counselors attended to an average 17 participants per day, consistent with recommended national figures for mass campaigns. Among women, HIV infection varied by age, and was more likely with an ended marriage (e.g. widowed vs. never married, OR.3.91; 95% CI. 2.87-5.34), and lack of occupation. In men, quantitatively stronger relationships were found (e.g. widowed vs. never married, OR.7.0; 95% CI. 3.5-13.9). Always using condoms with a non-steady partner was more common among HIV-infected women participants who knew their status compared to those who did not (OR.5.4 95% CI. 2.3-12.8).ConclusionThrough integrated campaigns it is feasible to efficiently cover large proportions of eligible adults in rural underserved communities with multiple disease preventive services simultaneously achieving various national and international health development goals.
Published: 2010

30. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis.

Author: Ubuka, Takayoshi, Morgan, Kevin, Pawson, Adam J, Osugi, Tomohiro, Chowdhury, Vishwajit S, Minakata, Hiroyuki, Tsutsui, Kazuyoshi, Millar, Robert P, and Bentley, George E
Subjects: Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Neurons, Humans, Glycoproteins, Neuropeptides, Receptors, Neuropeptide, RNA, Messenger, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Amino Acid Sequence, Sequence Homology, Amino Acid, Molecular Sequence Data, Adult, RNA, Messenger, Receptors, Neuropeptide, Sequence Homology, Amino Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, General Science & Technology
Abstract: The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH(2)) which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH(2) (human RFRP-1) and VPNLPQRF-NH(2) (human RFRP-3) by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes). Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca(2+) mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3) in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions.
Published: 2009

31. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation

Author: Gu, Bingnan, Sun, Peng, Yuan, Yuanyang, Moraes, Ricardo C, Li, Aihua, Teng, Andy, Agrawal, Anshu, Rhéaume, Catherine, Bilanchone, Virginia, Veltmaat, Jacqueline M, Takemaru, Ken-Ichi, Millar, Sarah, Lee, Eva Y-HP, Lewis, Michael T, Li, Boan, and Dai, Xing
Subjects: Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Genetics, Biological Sciences, Regenerative Medicine, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Animals, Cell Cycle, Cell Proliferation, Gene Expression Regulation, Histone Methyltransferases, Histone-Lysine N-Methyltransferase, Histones, Humans, Intracellular Signaling Peptides and Proteins, Lysine, Mammary Glands, Animal, Methylation, Mice, Phenotype, Stem Cells, Wnt Proteins, beta Catenin, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract: Recent studies have unequivocally identified multipotent stem/progenitor cells in mammary glands, offering a tractable model system to unravel genetic and epigenetic regulation of epithelial stem/progenitor cell development and homeostasis. In this study, we show that Pygo2, a member of an evolutionarily conserved family of plant homeo domain-containing proteins, is expressed in embryonic and postnatal mammary progenitor cells. Pygo2 deficiency, which is achieved by complete or epithelia-specific gene ablation in mice, results in defective mammary morphogenesis and regeneration accompanied by severely compromised expansive self-renewal of epithelial progenitor cells. Pygo2 converges with Wnt/beta-catenin signaling on progenitor cell regulation and cell cycle gene expression, and loss of epithelial Pygo2 completely rescues beta-catenin-induced mammary outgrowth. We further describe a novel molecular function of Pygo2 that is required for mammary progenitor cell expansion, which is to facilitate K4 trimethylation of histone H3, both globally and at Wnt/beta-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes.
Published: 2009

32. A method for identifying the learning curve for the surgical stabilization of rib fractures

Author: Aaron M, Delman, Kevin M, Turner, Allison M, Ammann, D A, Millar, Michael D, Goodman, and Christopher F, Janowak
Subjects: Fracture Fixation, Internal, Rib Fractures, Humans, Surgery, Critical Care and Intensive Care Medicine, Bone Plates, Learning Curve, Retrospective Studies
Abstract: Surgical stabilization of rib fractures (SSRF) is an accepted efficacious treatment modality for patients with severe chest wall injuries. Despite increased adoption of SSRF, surgical learning curves are unknown. We hypothesized intraoperative duration could define individual SSRF learning curves.Consecutive SSRF operations between January 2017 and December 2021 at a single institution were reviewed. Operative time, as measured from incision until skin closure, was evaluated by cumulative sum methodology using a range of acceptable "missteps" to determine the learning curves. Misstep was defined by extrapolation of accumulated operative time data.Eighty-three patients underwent SSRF by three surgeons during this retrospective review. Average operative times ranged from 135 minutes for two plates to 247 minutes for seven plates. Using polynomial regression of average operative times, 75 minutes for general procedural requirements plus 35 minutes per plate were derived as the anticipated operative times per procedure. Cumulative sum analyses using 5%, 10%, 15%, and 20% incident rates for not meeting expected operative times, or "missteps" were used. An institutional learning curve between 15 and 55 SSRF operations was identified assuming a 90% performance rate. An individual learning curve of 15 to 20 operations assuming a 90% performance rate was observed. After this period, operative times stabilized or decreased for surgeons A, B, and C.The institutional and individual surgeon learning curves for SSRF appears to steadily improve after 15 to 20 operations using operative time as a surrogate for performance. The implementation of SSRF programs by trauma/acute care surgeons is feasible with an attainable learning curve.Therapeutic/Care Management; Level IV.
Published: 2022

33. The molecular basis of cereal grain proteostasis

Author: Hui Cao, Owen Duncan, and A. Harvey Millar
Subjects: Proteostasis, Humans, Edible Grain, Molecular Biology, Biochemistry, Plant Proteins
Abstract: Storage proteins deposited in the endosperm of cereal grains are both a nitrogen reserve for seed germination and seedling growth and a primary protein source for human nutrition. Detailed surveys of the patterns of storage protein accumulation in cereal grains during grain development have been undertaken, but an in-depth understanding of the molecular mechanisms that regulate these patterns is still lacking. Accumulation of storage proteins in cereal grains involves a series of subcellular compartments, a set of energy-dependent events that compete with other cellular processes, and a balance of protein synthesis and protein degradation rates at different times during the developmental process. In this review, we focus on the importance of rates in cereal grain storage protein accumulation during grain development and outline the potential implications and applications of this information to accelerate modern agriculture breeding programmes and optimize energy use efficiency in proteostasis.
Published: 2022

34. Therapeutic inertia amongst general practitioners with interest in diabetes

Author: Richard Brice, Richard Quigley, Rahul Mohan, Pam Brown, Azhar Zafar, Amrit Lamba, Naresh Kanumilli, Deb Kar, Ahmed Amjad, Nigel Campbell, Tun Than, Rizwan Hussain, Mukesh Mistry, Kevin Fernando, Joan St. John, Elizabeth Martin, Jim McMoran, Colin Kenny, Samuel Seidu, Kamlesh Khunti, David Millar-Jones, Mathew Capehorn, and Shahzada Kahn
Subjects: Blood Glucose, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Attitude of Health Personnel, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Audit, Primary care, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, General Practitioners, Risk Factors, Diabetes mellitus, Health care, Internal Medicine, Full model, Humans, Hypoglycemic Agents, Medicine, 030212 general & internal medicine, Practice Patterns, Physicians', Intensive care medicine, Aged, Retrospective Studies, Therapeutic inertia, Glycated Hemoglobin, Medical Audit, Nutrition and Dietetics, Primary Health Care, business.industry, Middle Aged, medicine.disease, United Kingdom, Care in the Community, Diabetes Mellitus, Type 2, Practice Guidelines as Topic, Physical therapy, Female, Guideline Adherence, Family Practice, business, Biomarkers
Abstract: Introduction: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. Methods: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Results: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p = 0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Conclusion: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.
Published: 2023

35. GWAS and meta-analysis identifies 49 genetic variants underlying critical Covid-19

Author: Pairo-Castineira, Erola, Rawlik, Konrad, Bretherick, Andrew D, Qi, Ting, Wu, Yang, Nassiri, Isar, McConkey, Glenn A., Zechner, Marie, Klaric, Lucija, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Richmond , Anne, Millar, Jonathan, Russell, Clark D, Malinauskas, Tomas, Thwaites, Ryan, Morrice, Kirstie, Keating, Sean, Maslove, David M, Nichol, Alistair D, Semple, Malcolm Gracie, Knight, Julian, Shankar-Hari, Manu, Summers, Charlotte, Hinds , Charles, Horby, Peter, Ling, Lowell, McAuley, Danny F., Montgomery, Hugh, Openshaw, Peter J.M., Begg, Colin, Walsh, Timothy S., Tenesa, Albert, Flores, Carlos, Riancho, Jose A., Rojas-Martinez, Augusto, Lapunzina, Pablo, Yang, Jian, Ponting, Chris P, Wilson, James F, Vitart, Veronique, Abedalthagafi, Malak S, Luchessi, Andre, Parra, Esteban J, Cruz, Raquel, Carracedo, Angel, Fawkes, Angie, Murphy, Lee, Rowan, Kathy, Pereira, Alexandre C, Law, Andy, Fairfax, Benjamin P, Clohisey Hendry, Sara, and Baillie, J Kenneth
Subjects: Phenotype, Genetic Variation/genetics, Genotype, Genotyping Techniques, Whole Genome Sequencing, Monocytes/metabolism, Critical Illness, Genetic Predisposition to Disease/genetics, rab GTP-Binding Proteins/genetics, Humans, Transcriptome, COVID-19/genetics, Genome-Wide Association Study
Abstract: Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
Published: 2023

36. Action potential amplitude and baroreflex resetting of action potential clusters mediate hypoxia‐induced sympathetic long‐term facilitation

Author: Brooke M. Shafer, Anthony V. Incognito, Tyler D. Vermeulen, Massimo Nardone, André L. Teixeira, Stephen A. Klassen, Philip J. Millar, and Glen E. Foster
Subjects: Adult, Male, Young Adult, Sympathetic Nervous System, Heart Rate, Physiology, Action Potentials, Humans, Arterial Pressure, Blood Pressure, Baroreflex, Hypoxia, Muscle, Skeletal
Abstract: Baroreflex resetting permits sympathetic long-term facilitation (sLTF) following hypoxia; however, baroreflex control of action potential (AP) clusters and AP recruitment patterns facilitating sLTF is unknown. We hypothesized that baroreflex resetting of arterial pressure operating points (OPs) of AP clusters and recruitment of large-amplitude APs would mediate sLTF following hypoxia. Eight men (age: 24 (3) years; body mass index: 24 (3) kg/m
Published: 2022

37. Autonomic modulation in heart failure patients by cardiopulmonary rehabilitation: who benefits?

Author: Catherine F Notarius, Daniel A Keir, Mark B Badrov, Philip J Millar, Paul Oh, and John S Floras
Subjects: Heart Failure, Exercise Tolerance, Oxygen Consumption, Epidemiology, Humans, Heart, Stroke Volume, Autonomic Nervous System, Cardiology and Cardiovascular Medicine
Published: 2022

38. Sympathetic transduction of blood pressure during graded lower body negative pressure in young healthy adults

Author: Massimo Nardone, Carlin Katerberg, André L. Teixeira, Jordan B. Lee, Julian C. Bommarito, and Philip J. Millar
Subjects: Adult, Lower Body Negative Pressure, Cross-Sectional Studies, Sympathetic Nervous System, Heart Rate, Physiology, Physiology (medical), Humans, Blood Pressure, Female, Muscle, Skeletal
Abstract: Sympathetic transduction of blood pressure (BP) is correlated negatively with resting muscle sympathetic nerve activity (MSNA) in cross-sectional data, but the acute effects of increasing MSNA are unclear. Sixteen (4 female) healthy adults (26 ± 3 years) underwent continuous measurement of heart rate, BP, and MSNA at rest and during graded lower body negative pressure (LBNP) at −10, −20, and −30 mmHg. Sympathetic transduction of BP was quantified in the time (signal averaging) and frequency (MSNA-BP gain) domains. The proportions of MSNA bursts firing within each tertile of BP were calculated. As expected, LBNP increased MSNA burst frequency ( P < 0.01) and burst amplitude ( P < 0.02), although the proportions of MSNA bursts firing across each BP tertile remained stable (all P > 0.44). The MSNA-diastolic BP low-frequency transfer function gain ( P = 0.25) was unchanged during LBNP; the spectral coherence was increased ( P = 0.03). Signal-averaged sympathetic transduction of diastolic BP was unchanged (from 2.1 ± 1.0 at rest to 2.4 ± 1.5, 2.2 ± 1.3, and 2.3 ± 1.4 mmHg; P = 0.43) during LBNP, but diastolic BP responses following nonburst cardiac cycles progressively decreased (from −0.8 ± 0.4 at rest to −1.0 ± 0.6, −1.2 ± 0.6, and −1.6 ± 0.9 mmHg; P < 0.01). As a result, the difference between MSNA burst and nonburst diastolic BP responses was increased (from 2.9 ± 1.4 at rest to 3.4 ± 1.9, 3.4 ± 1.9, and 3.9 ± 2.1 mmHg; P < 0.01). In conclusion, acute increases in MSNA using LBNP did not alter traditional signal-averaged or frequency-domain measures of sympathetic transduction of BP or the proportion of MSNA bursts firing at different BP levels. The factors that determine changes in the firing of MSNA bursts relative to oscillations in BP require further investigation.
Published: 2022

39. Dietary score associations with markers of chronic low-grade inflammation: a cross-sectional comparative analysis of a middle- to older-aged population

Author: Seán R. Millar, Pilar Navarro, Janas M. Harrington, Nitin Shivappa, James R. Hébert, Ivan J. Perry, and Catherine M. Phillips
Subjects: Inflammation, Male, Cross-Sectional Studies, Nutrition and Dietetics, Interleukin-6, Tumor Necrosis Factor-alpha, Humans, Medicine (miscellaneous), Female, Middle Aged, Biomarkers, Aged, Diet
Abstract: Purpose To assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Mediterranean Diet (MD), Dietary Inflammatory Index (DII®) and Energy-adjusted DII (E-DII™) scores and pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. Methods This was a cross-sectional study of 1862 men and women aged 46–73 years, randomly selected from a large primary care centre in Ireland. DASH, MD, DII and E-DII scores were derived from validated food frequency questionnaires. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with biomarker concentrations. Results In fully adjusted models, higher diet quality or a less pro-inflammatory diet was associated with lower concentrations of c-reactive protein, neutrophils (all dietary scores), complement component 3 [C3], interleukin 6 [IL-6], tumour necrosis factor-alpha [TNF-α], white blood cell count [WBC], the neutrophil-to-lymphocyte ratio [NLR] (DASH, DII and E-DII), monocytes (DASH and DII) and resistin (DII and E-DII). After accounting for multiple testing, relationships with C3 (DASH: β = − 2.079, p = .011 and DII: β = 2.521, p = .036), IL-6 (DASH: β = − 0.063, p = .011), TNF-α (DASH: β = − 0.027, p = .034), WBC (DASH: β = − 0.028, p = .001 and DII: β = 0.029, p = .02), neutrophils (DASH: β = − 0.041, p = .001; DII: β = 0.043, p = .007; E-DII: β = 0.029, p = .009) and the NLR (DASH: β = − 0.035, p = .011) persisted. Conclusions Better diet quality, determined by the DASH score, may be more closely associated with inflammatory biomarkers related to health in middle- to older-aged adults than the MD, DII and E-DII scores.
Published: 2022

40. 3D modelling of tibial plateau fractures: Variability in fracture location and characteristics across Schatzker fracture types

Author: François Fraysse, Stuart C. Millar, Lucian B. Solomon, Dominic Thewlis, John B. Arnold, Millar, Stuart C, Fraysse, Francois, Arnold, John B, Thewlis, Dominic, and Solomon, Lucian B
Subjects: Male, CT reconstruction, 3d model, Imaging data, Condyle, Fracture Fixation, Internal, 03 medical and health sciences, 0302 clinical medicine, Tibial plateau fracture, Humans, Medicine, Fracture type, Retrospective Studies, General Environmental Science, Orthodontics, 030222 orthopedics, geography, Plateau, geography.geographical_feature_category, Tibia, business.industry, 030208 emergency & critical care medicine, Articular surface, medicine.disease, 3D modelling, Tibial Fractures, classification, Fracture (geology), General Earth and Planetary Sciences, Female, Joints, tibial plateau fracture, Tomography, X-Ray Computed, business
Abstract: Introduction: Numerous classifications have been developed to assess tibial plateau fractures (TPF). Of these, the Schatzker system is the most widely reported in the literature yet this system is limited in its characterisation of morphological fracture features underlying the fracture location. The purpose of this study was to compare 3D morphological features of TPFs across different Schatzker types. Methods: This study retrospectively analysed preoperative TPF imaging data to reconstruct 3D models of the fractures. Ninety-one fractures (29 female, 62 male) were analysed and classified using Schatzker. Fracture location across Schatzker types was compared based on division of the articular surface into six ‘zones’. Additionally, morphological characteristics of the fractures were compared based on fracture type, including; the number, volume and shape of the fragments. Results: Schatzker II, IV and VI fractures were most common, making up 41%, 16% and 20%, respectively. Type II fractures commonly involved both the lateral and central aspect of the tibial plateau, similarly, type IV fractures incorporated the lateral condyle in most cases. Considering the morphological metrics, statistically significant differences were observed between Schatzker types for the number of; total, articular, cortical and volumetrically significant (all P < 0.001) fragments along with the volume of both primary (P < 0.001) and secondary (P = 0.02) fragments. Discussion: Assessment of underlying fracture characteristics in addition to fracture location can serve to provide greater detail relating to fracture morphology, which has the potential to assist with both surgical decision making and assessment of postoperative outcomes. Incorporating this information as part of a hierarchical or multifactorial framework for classifying fractures may help distinguish subtle differences between fracture types that are classifiable using the most current systems. Refereed/Peer-reviewed
Published: 2021

41. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Author: Maddali, Manoj V, Churpek, Matthew, Pham, Tai, Rezoagli, Emanuele, Zhuo, Hanjing, Zhao, Wendi, June, He, Delucchi, Kevin L, Wang, Chunxue, Wickersham, Nancy, Mcneil, J Brennan, Jauregui, Alejandra, Serena, Ke, Vessel, Kathryn, Gomez, Antonio, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Sarma, Aartik, Leligdowicz, Aleksandra, Liu, Kathleen D, Matthay, Michael A, Ware, Lorraine B, Laffey, John G, Bellani, Giacomo, Calfee, Carolyn S, Sinha, Pratik, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Pham, Tài, Wrigge, Hermann, Matamis, Dimitrios, Ranero, Jorge Luis, Hashemian, S. M, Amin, Pravin, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M, Laake, Jon Henrik, Palo, Jose Emmanuel, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicolas, Lorente, Jose A, Larsson, Anders, Piquilloud, Lise, Abroug, Fekri, Mcauley, Daniel F, Mcnamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Francois, Guy M, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Insaurralde, Carolina S, Alejandro, Risso V, Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O, Cardonnet, Luis P, Bettini, Lisandro R, Bisso, Mariano Carboni, Osman, Emilio M, Setten, Mariano G, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Milstein, Cesar, Pozo, Norberto C, Grubissich, Nicolas, Plotnikow, Gustavo A, Vasquez, Daniela N, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A, Saenz, María G, Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E, Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Anders, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Piras, Claudio, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, Youzhong, An, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Zheng L, Ye, Wang, Wei, Wenwen, Li, Qingdong, Li, Zheng, Ruiqiang, Wenkui, Yu, Shen, Juanhong, Xinyu, Li, Tao, Yu, Weihua, Lu, Ya Q, Wu, Huang, Xiao B, Zhenyang, He, Yuanhua, Lu, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Bin, Li, Liu, Jing L, Zhou, Fa C, Qiong J, Li, Zhang, Xing 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Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Siu-Ming, Au, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D, Meybohm, Patrick, Reske, Andreas W, Simon, Philipp, Hopf, Hans-Bernd F, Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N, Papavasilopoulou, Theonymfi G, Zacharas, Giannis A, Ourailogloy, Vasilis, Mouloudi, Eleni K, Massa, Eleni V, Nagy, Eva O, Stamou, Electra E, Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Schultz, Marcus J, Goodson, Jennifer C, Rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J, Andersen, Finn H, Dolva, Merete S, Laake, Jon H, Barratt-Due, Andreas, Noremark, Kim Andre L, Søreide, Eldar, Sjøbø, Brit Å, Guttormsen, Anne B, Yoshido, Hector H Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A Montes, Alisasis, Alain U, Robles, Joanne B, Pasanting-Lim, Rossini Abbie B, Tan, Beatriz C, Andruszkiewicz, Pawel, Jakubowska, Karina, Cox, Cristina M, Alvarez, António M, Oliveira, Bruno S, Montanha, Gustavo M, Barros, Nelson C, Pereira, Carlos S, Messias, António M, Monteiro, Jorge M, Araujo, Ana M, Catorze, Nuno T, Marum, Susan M, Bouw, Maria J, Gomes, Rui M, Brito, Vania A, Castro, Silvia, Estilita, Joana M, Barros, Filipa M, Serra, Isabel M, Martinho, Aurelia M, Tomescu, Dana R, Marcu, Alexandra, Bedreag, Ovidiu H, Papurica, Marius, Corneci, Dan E, Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I, Gazenkampf, Andrey A, Almekhlafi, Ghaleb, Albarrak, Mohamad M, Mustafa, Ghanem M, Maghrabi, Khalid A, Salahuddin, Nawal, Aisa, Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Mª Teresa, Arizmendi, Alfons, Piacentini, Enrique A, Franco, Nieves, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G, Alonso, Javier G, Alda, Rosa S, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Blasco Navalpotro, Miguel Angel, Abad, Ricardo Diaz, Montiel González, Raquel, Toribio, Dácil Parrilla, Castro, Alejandro G, Artiga, Maria Jose D, Penuelas, Oscar, Roser, Tomas P, Olga, Moreno F, Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P, Elisabet, Garcia M, Claverias, Laura, Magret, Monica, Pellicer, Ana M, Rodriguez, Lucia L, Sánchez-Ballesteros, Jesús, González-Salamanca, Ángela, Jimenez, Antonio G, Huerta, Francisco P, Diaz, Juan Carlos J Sotillo, Lopez, Esther Bermejo, Moya, David D Llinares, Alfonso, Alec A Tallet, Eugenio Luis, Palazon Sanchez, Cesar, Palazon Sanchez, Rafael, Sánchez I, Virgilio, Corcoles G, Recio, Noelia N, Adamsson, Richard O, Rylander, Christian C, Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lars, Helleberg, Johan, Eriksson, Karin E, Glietsch, Rita, Larsson, Niklas, Nygren, Ingela, Nunes, Silvia L, Morin, Anna-Karin, Kander, Thomas, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O, Derman, Suleyman S, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, Mcauley, Danny, Steinberg, Jack, Hopkins, Phil, Mellis, Clare, Stansil, Frank, Kakar, Vivek, Hadfield, Dan, Brown, Christine, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K, Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S, Fawkes, Danielle A, Watt, Philip, Twohey, Linda, Thomas, Rajeev R Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J, Hormis, Anil P, Kannan, Santhana G, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolcs, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J, Ellis, Helen E, Mckechnie, Stuart, Hutton, Paula J, Di Tomasso, Nora N, Vitale, Michela N, Griffin, Ruth O, Dean, Michael N, Cranshaw, Julius H, Willett, Emma L, Ioannou, Nicholas, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tamas, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thomas, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, Pillai, Suresh, Kajtor, Istvan, Sivashanmugave, Mageswaran, Okane, Sinead C, Donnelly, Adrian, Frigyik, Aniko D, Careless, Jon P, May, Martin M, Stewart, Richard, Trinder, T John, Hagan, Samantha J, Wise, Matt P, Cole, Jade M, Macfie, Caroline C, Dowling, Anna T, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C, Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M, Beitler, Jeremy R, Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn Iii, John O, Gomaa, Dina, Tainter, Christopher, Cowley, R Adams, Yeatts, Dale J, Warren, Jessica, Lanspa, Michael J, Miller, Russel R, Grissom, Colin K, Brown, Samuel M, Bauer, Philippe R, Gosselin, Ryan J, Kitch, Barrett T, Cohen, Jason E, Beegle, Scott H, Gueret, Renaud M, Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G, Lamb, Keith D, Oetting, Trevor W, Mohr, Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, Angela, Elmasri, Mary, Crouch, Daniel R, Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Brazzi, L, Maddali, M. V., Churpek, M., Pham, T., Rezoagli, E., Zhuo, H., Zhao, W., He, J., Delucchi, K. L., Wang, C., Wickersham, N., Mcneil, J. B., Jauregui, A., Ke, S., Vessel, K., Gomez, A., Hendrickson, C. M., Kangelaris, K. N., Sarma, A., Leligdowicz, A., Liu, K. D., Matthay, M. A., Ware, L. B., Laffey, J. G., Bellani, G., Calfee, C. S., Sinha, P., Rios, F., Van Haren, F., Sottiaux, T., Lora, F. S., Azevedo, L. C., Depuydt, P., Fan, E., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Wrigge, H., Matamis, D., Ranero, J. L., Hashemian, S. M., Amin, P., Clarkson, K., Kurahashi, K., Villagomez, A., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Palo, J. E., do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J. A., Larsson, A., Piquilloud, L., Abroug, F., Mcauley, D. F., Mcnamee, L., Hurtado, J., Bajwa, E., Dempaire, G., Francois, G. M., Sula, H., Nunci, L., Cani, A., Zazu, A., Dellera, C., Insaurralde, C. S., Alejandro, R. 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Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francoi, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya Q, Huang, Xiao B, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L, Zhou, Fa C, Li, Qiong J, Zhang, Xing Y, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N, Zhao, Xian Y, Li, Yuan Y, Li, Xiao L, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q, Zhu, Wei H, Hang, Ai Y, Hua, Ma X, Li, Yimin, Xu, Yonghao, Di, Yu D, Ling, Long L, Qin, Tie H, Wang, Shou H, Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P, Silesky Jimenez, Juan I, González Rojas, Manuel A, Solis-Quesada, Jaime E, Ramirez-Alfaro, Christian M, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G, Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicola, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicola, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicola, Chiche, Jean-Daniel, Daviaud, Fabrice, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Deni, Arnal, Jean-Michel, Briquet, Anai, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelo, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Franci, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacque, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jen, Schäfer, Susanne, Zacharowski, Kai D, Meybohm, Patrick, Reske, Andreas W, Simon, Philipp, Hopf, Hans-Bernd F, Schuetz, Michael, Baltus, Thoma, Papanikolaou, Metaxia N, Papavasilopoulou, Theonymfi G, Zacharas, Giannis A, Ourailogloy, Vasili, Mouloudi, Eleni K, Massa, Eleni V, Nagy, Eva O, Stamou, Electra E, Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Oleg, Oss, Peteri, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flore, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Schultz, Marcus J, Goodson, Jennifer C, rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J, Andersen, Finn H, Dolva, Merete S, Laake, Jon H, Barratt-Due, Andrea, Noremark, Kim Andre L, Søreide, Eldar, Sjøbø, Brit Å, Guttormsen, Anne B, Yoshido, Hector H Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A Monte, Alisasis, Alain U, Robles, Joanne B, Pasanting-Lim, Rossini Abbie B, Tan, Beatriz C, Andruszkiewicz, Pawel, Jakubowska, Karina, Cox, Cristina M, Alvarez, António M, Oliveira, Bruno S, Montanha, Gustavo M, Barros, Nelson C, Pereira, Carlos S, Messias, António M, Monteiro, Jorge M, Araujo, Ana M, Catorze, Nuno T, Marum, Susan M, Bouw, Maria J, Gomes, Rui M, Brito, Vania A, Castro, Silvia, Estilita, Joana M, Barros, Filipa M, Serra, Isabel M, Martinho, Aurelia M, Tomescu, Dana R, Marcu, Alexandra, Bedreag, Ovidiu H, Papurica, Mariu, Corneci, Dan E, Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I, Gazenkampf, Andrey A, Almekhlafi, Ghaleb, Albarrak, Mohamad M, Mustafa, Ghanem M, Maghrabi, Khalid A, Salahuddin, Nawal, Aisa, Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marco, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesia, Jurado, Mª Teresa, Arizmendi, Alfon, Piacentini, Enrique A, Franco, Nieve, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G, Alonso, Javier G, Alda, Rosa S, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Blasco Navalpotro, Miguel Angel, Abad, Ricardo Diaz, Montiel González, Raquel, Toribio, Dácil Parrilla, Castro, Alejandro G, Artiga, Maria Jose D, Penuelas, Oscar, Roser, Tomas P, Olga, Moreno F, Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P, Elisabet, Garcia M, Claverias, Laura, Magret, Monica, Pellicer, Ana M, Rodriguez, Lucia L, Sánchez-Ballesteros, Jesú, González-Salamanca, Ángela, Jimenez, Antonio G, Huerta, Francisco P, Diaz, Juan Carlos J Sotillo, Lopez, Esther Bermejo, Moya, David D Llinare, Alfonso, Alec A Tallet, Eugenio Luis, Palazon Sanchez, Cesar, Palazon Sanchez, Rafael, Sánchez I, Virgilio, Corcoles G, Recio, Noelia N, Adamsson, Richard O, Rylander, Christian C, Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Han, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lar, Helleberg, Johan, Eriksson, Karin E, Glietsch, Rita, Larsson, Nikla, Nygren, Ingela, Nunes, Silvia L, Morin, Anna-Karin, Kander, Thoma, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O, Derman, Suleyman S, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Steinberg, Jack, Hopkins, Phil, Mellis, Clare, Stansil, Frank, Kakar, Vivek, Hadfield, Dan, Brown, Christine, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K, Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S, Fawkes, Danielle A, Watt, Philip, Twohey, Linda, Thomas, Rajeev R Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J, Hormis, Anil P, Kannan, Santhana G, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolc, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J, Ellis, Helen E, Mckechnie, Stuart, Hutton, Paula J, Di Tomasso, Nora N, Vitale, Michela N, Griffin, Ruth O, Dean, Michael N, Cranshaw, Julius H, Willett, Emma L, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thoma, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, Pillai, Suresh, Kajtor, Istvan, Sivashanmugave, Mageswaran, Okane, Sinead C, Donnelly, Adrian, Frigyik, Aniko D, Careless, Jon P, May, Martin M, Stewart, Richard, Trinder, T John, Hagan, Samantha J, Wise, Matt P, Cole, Jade M, MacFie, Caroline C, Dowling, Anna T, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C, Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M, Beitler, Jeremy R, Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn Iii, John O, Gomaa, Dina, Tainter, Christopher, Cowley, R Adam, Yeatts, Dale J, Warren, Jessica, Lanspa, Michael J, Miller, Russel R, Grissom, Colin K, Brown, Samuel M, Bauer, Philippe R, Gosselin, Ryan J, Kitch, Barrett T, Cohen, Jason E, Beegle, Scott H, Gueret, Renaud M, Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G, Lamb, Keith D, Oetting, Trevor W, Mohr, Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, Angela, Elmasri, Mary, Crouch, Daniel R, Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, ACS - Diabetes & metabolism, ACS - Microcirculation, Maddali, M, Churpek, M, Pham, T, Rezoagli, E, Zhuo, H, Zhao, W, He, J, Delucchi, K, Wang, C, Wickersham, N, Mcneil, J, Jauregui, A, Ke, S, Vessel, K, Gomez, A, Hendrickson, C, Kangelaris, K, Sarma, A, Leligdowicz, A, Liu, K, Matthay, M, Ware, L, Laffey, J, Bellani, G, Calfee, C, and Sinha, P
Subjects: Pulmonary and Respiratory Medicine, Clinical Sciences, Acute Lung Injury, Article, Machine Learning, Positive-Pressure Respiration, Rare Diseases, Clinical Research, Retrospective Studie, Settore MED/41 - ANESTESIOLOGIA, Humans, Lung, Acute Respiratory Distress Syndrome, Retrospective Studies, Respiratory Distress Syndrome, Other Medical and Health Sciences, LUNG SAFE Investigators and the ESICM Trials Group, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Phenotype, Good Health and Well Being, Area Under Curve, ARDS: Phenotype, Respiratory, Public Health and Health Services, ARDS, Human
Abstract: Item does not contain fulltext BACKGROUND: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. METHODS: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. FINDINGS: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p
Published: 2022

42. Anti-Cholestatic Therapy with Obeticholic Acid Improves Short-Term Memory in Bile Duct-Ligated Mice

Author: Lucy M.V. Gee, Ben Barron-Millar, Jack Leslie, Claire Richardson, Marco Y.W. Zaki, Saimir Luli, Rachel A. Burgoyne, Rainie I.T. Cameron, Graham R. Smith, John G. Brain, Barbara Innes, Laura Jopson, Jessica K. Dyson, Katherine R.C. McKay, Alexandros Pechlivanis, Elaine Holmes, Rolando Berlinguer-Palmini, Stella Victorelli, George F. Mells, Richard N. Sandford, Jeremy Palmer, John A. Kirby, Christos Kiourtis, Joao Mokochinski, Zoe Hall, Thomas G. Bird, Lee A. Borthwick, Christopher M. Morris, Peter S. Hanson, Diana Jurk, Elizabeth A. Stoll, Fiona E.N. LeBeau, David E.J. Jones, Fiona Oakley, Sandford, Richard [0000-0002-7437-0560], and Apollo - University of Cambridge Repository
Subjects: cognition, therapy, senescence, Cholestasis, Chenodeoxycholic Acid, Pathology and Forensic Medicine, Mice, Memory, Short-Term, Liver, Humans, Animals, Bile Ducts, cholestasis, Ligation
Abstract: Patients with cholestatic liver disease, including those with primary biliary cholangitis, can experience symptoms of impaired cognition or brain fog. This phenomenon remains unexplained and is currently untreatable. Bile duct ligation (BDL) is an established rodent model of cholestasis. In addition to liver changes, BDL animals develop cognitive symptoms early in the disease process (before development of cirrhosis and/or liver failure). The cellular mechanisms underpinning these cognitive symptoms are poorly understood. Herein, the study explored the neurocognitive symptom manifestations, and tested potential therapies, in BDL mice, and used human neuronal cell cultures to explore translatability to humans. BDL animals exhibited short-term memory loss and showed reduced astrocyte coverage of the blood-brain barrier, destabilized hippocampal network activity, and neuronal senescence. Ursodeoxycholic acid (first-line therapy for most human cholestatic diseases) did not reverse symptomatic or mechanistic aspects. In contrast, obeticholic acid (OCA), a farnesoid X receptor agonist and second-line anti-cholestatic agent, normalized memory function, suppressed blood-brain barrier changes, prevented hippocampal network deficits, and reversed neuronal senescence. Co-culture of human neuronal cells with either BDL or human cholestatic patient serum induced cellular senescence and increased mitochondrial respiration, changes that were limited again by OCA. These findings provide new insights into the mechanism of cognitive symptoms in BDL animals, suggesting that OCA therapy or farnesoid X receptor agonism could be used to limit cholestasis-induced neuronal senescence.
Published: 2023
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43. Because Excellencism Is More than Good Enough: On the Need to Distinguish the Pursuit of Excellence from the Pursuit of Perfection

Author: Patrick Gaudreau, Benjamin J. I. Schellenberg, Alexandre Gareau, Kristina Kljajic, and Stéphanie Manoni-Millar
Subjects: Sociology and Political Science, Social Psychology, Educational Status, Humans, Perfectionism, Factor Analysis, Statistical, Students
Abstract: An unresolved and controversial issue in the perfectionism literature is whether perfectionism is beneficial, harmful, or unneeded. The Model of Excellencism and Perfectionism (MEP) was recently developed to address this question by distinguishing the pursuit of perfection from the pursuit of excellence (Gaudreau, 2019). In this article, we report the results of the first empirical test of the core assumptions of the MEP. Across 5 studies (total N = 2,157), we tested the conceptual, functional, and developmental distinctiveness of excellencism and perfectionism. In Study 1, exploratory and confirmatory factor analyses with two samples supported the hypothesized two-factor structure of the newly developed Scale of Perfectionism and Excellencism (SCOPE). Study 2 provided evidence of convergent and discriminant validity from scores obtained from the SCOPE, and showed that, over and above excellencism, perfectionism was not associated with additional benefits (e.g., life satisfaction) or harms (e.g., depression). Studies 3-4 focused on the academic achievement of undergraduates and showed that, compared to excellence strivers, perfection strivers more often aimed for perfect A+ grades (Study 3), but in fact achieved worse grades (Study 4). Study 5 adopted a four-wave longitudinal design with undergraduates and showed that excellencism and perfectionism were associated with an upward and a downward spiral of academic development. Overall, the results support the core assumptions of the MEP and show that perfectionism is either unneeded or harmful.
Published: 2023

44. Factors correlating with survival following adjuvant or definitive radiosurgery for large brain metastases

Author: Enrique Gutiérrez-Valencia, Aristotelis Kalyvas, Conrad J Villafuerte, Barbara-Ann Millar, Normand Laperriere, Tatiana Conrad, Alejandro Berlin, Jessica Weiss, Gelareh Zadeh, Mark Bernstein, Paul Kongkham, and David B Shultz
Subjects: Cancer Research, Oncology, Brain Neoplasms, Incidence, Multivariate Analysis, parasitic diseases, Clinical Investigations, Humans, Neurology (clinical), Radiosurgery, Retrospective Studies
Abstract: Background We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4 cc) brain metastases (BrM). Methods We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. Results We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P < .001), BrM quantity [HR 1.13 (1.06–1.22) (P < .001)]; performance status (PS) [HR 2.78 (1.73–4.46) (P < .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P < .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46–073) (P < .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P < .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P < .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P < .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20–2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89–4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. Conclusion SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.
Published: 2022

45. Codesigning a patient support portal with health professionals and men with prostate cancer: An action research study

Author: Benjamin Shemesh, Jacinta Opie, Ellie Tsiamis, Darshini Ayton, Prassannah Satasivam, Paula Wilton, Karla Gough, Katrina Lewis, Colin O'Brien, Max Shub, Amanda Pomery, Christopher Mac Manus, Jeremy Millar, and Susan Evans
Subjects: Male, Victoria, Health Personnel, Public Health, Environmental and Occupational Health, Humans, Prostatic Neoplasms, Health Services Research, Focus Groups
Abstract: The supportive care needs of men with prostate cancer (PCa) have been well documented, but little is known about how an online portal may address these. This study sought to determine priority issues facing men with PCa, barriers and enablers to accessing care and whether health professionals (HPs) and men would support the inclusion of a patient-reported outcome (PRO) comparator tool.We conducted four online focus groups with HPs recruited from healthcare services in Victoria, followed by seven online codesign workshops with men with PCa, recruited through the Victorian Prostate Cancer Outcomes Registry, Prostate Cancer Foundation Australia and the Cancer Council Victoria. Men were eligible to participate if they had lived experience of PCa and access to the internet. We analysed focus groups thematically. Workshops were analysed using descriptive-content analysis.HPs (n = 39) highlighted that men had shifting priorities over time, but noted the importance of providing information to men in lay terms to assist in treatment decision-making and side-effect management. HPs identified key enablers to men accessing support services such as practice nurses, partners and having men share their stories with each other. HPs raised financial, cultural, geographic and emotional barriers to accessing supportive care. Inclusion of a PRO comparator tool received mixed support from HPs, with 41% (n = 16) supportive, 49% (n = 19) unsure and 10% (n = 4) not supportive. Men involved in workshops (n = 28) identified informational needs to assist in treatment decision-making and side-effect management as the top priority throughout care. Men described support groups and practice nurses as key enablers. Short consultation times and complex information were described as barriers. Unlike HPs, all men supported the inclusion of a PRO comparator tool in a portal.Our findings suggest that a patient support portal should provide information in lay terms that address the shifting priorities of men with PCa. Men with PCa would welcome the development of a portal to centralize support information and a PRO comparator tool to prompt health-seeking behaviour. Future research will implement these findings in the development of a portal, and pilot and evaluate the portal within a population-based sample.This project adopted a codesign approach including both men with PCa and HPs involved in PCa care. Men with PCa also formed part of the study's steering committee and consumer advisory groups. HPs were consulted in a serious of online focus groups. Subsequently, men with PCa and their support persons participated in workshops. Men with PCa were also involved in the preparation of this manuscript.
Published: 2022

46. Case study: Perspectives on the use of LEGO® bricks in the biochemistry classroom

Author: Shane Austin, Crystal-Ann Millar, and Sherena Christmas
Subjects: Biochemical Phenomena, Humans, Problem-Based Learning, Students, Molecular Biology, Biochemistry
Abstract: The use of LEGO® bricks in the higher education classroom has increased in the last two decades. This is no different in the STEM classroom and several disciplines, including physics, chemistry, and biology, have all made use of LEGO® bricks in some way to create models for active learning activities. Currently, the discipline to make the greatest use of LEGO® bricks is chemistry; only limited examples exist in biochemistry and the molecular life sciences. Here, we present the use of a LEGO® brick modelling activity in the introductory biochemistry classroom during the teaching of metabolism. We present student comments on the activity and the models that were generated by the students. Additionally, we focus on other instructor and project student-designed models for the teaching of ATP synthesis, gene regulation and restriction digestion. Interestingly, both the gene regulation and restriction digest activities were generated with the help of undergraduate students or recent graduates, by applying a backward design approach. This case study seeks to encourage more molecular life science educators to adopt the use of LEGO® bricks in their classrooms to engage in more active learning.
Published: 2022

47. Assessing the rate, natural history, and treatment trends of intracranial aneurysms in patients with intracranial dural arteriovenous fistulas

Author: Isaac Josh Abecassis, R. Michael Meyer, Michael R. Levitt, Jason P. Sheehan, Ching-Jen Chen, Bradley A. Gross, Ashley Lockerman, W. Christopher Fox, Waleed Brinjikji, Giuseppe Lanzino, Robert M. Starke, Stephanie H. Chen, Adriaan R. E. Potgieser, J. Marc C. van Dijk, Andrew Durnford, Diederik Bulters, Junichiro Satomi, Yoshiteru Tada, Amanda Kwasnicki, Sepideh Amin-Hanjani, Ali Alaraj, Edgar A. Samaniego, Minako Hayakawa, Colin P. Derdeyn, Ethan Winkler, Adib Abla, Pui Man Rosalind Lai, Rose Du, Ridhima Guniganti, Akash P. Kansagra, Gregory J. Zipfel, Louis J. Kim, Jay F. Piccirillo, Hari Raman, Kim Lipsey, Enrico Giordan, Roanna Vine, Harry J. Cloft, David F. Kallmes, Bruce E. Pollock, Michael J. Link, Jason Sheehan, Mohana Rao Patibandla, Dale Ding, Thomas Buell, Gabriella Paisan, Cory Kelly, Jonathan Duffill, Adam Ditchfield, John Millar, Jason Macdonald, Adam J. Polifka, Dimitri Laurent, Brian Hoh, Jessica Smith, L. Dade Lunsford, Brian T. Jankowitz, Santiago Ortega Gutierrez, David Hasan, Jorge A. Roa, James Rossen, Waldo Guerrero, Allen McGruder, Fady T. Charbel, Victor A. Aletich, Linda Rose-Finnell, Eric C. Peterson, Dileep R. Yavagal, Samir Sur, Yasuhisa Kanematsu, Nobuaki Yamamoto, Tomoya Kinouchi, Masaaki Korai, Izumi Yamaguchi, Yuki Yamamoto, Ryan R. L. Phelps, Michael Lawton, Martin Rutkowski, M. Ali Aziz-Sultan, Nirav Patel, Kai U. Frerichs, and Movement Disorder (MD)
Subjects: medicine.medical_specialty, External carotid artery, Population, Arteriovenous fistula, feeding artery aneurysm, vascular disorders, Aneurysm, Dural arteriovenous fistulas, medicine.artery, Outcome Assessment, Health Care, medicine, Humans, cardiovascular diseases, education, dural arteriovenous fistula, Retrospective Studies, Central Nervous System Vascular Malformations, education.field_of_study, business.industry, Intracranial Aneurysm, General Medicine, medicine.disease, Embolization, Therapeutic, Surgery, Natural history, Concomitant, Cohort, cardiovascular system, business
Abstract: OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.
Published: 2022

48. Binocular Alignment Changes Between Sitting and Supine Positions in Patients with Dizziness

Author: Matthew Ryan Tan, Jorge Serrador, Jamie Perin, Yoav Gimmon, Jennifer Millar, Kelly Brewer, Dan Gold, and Michael C. Schubert
Subjects: Sitting Position, Otorhinolaryngology, Supine Position, Vertigo, Humans, Reflex, Vestibulo-Ocular, Dizziness, Sensory Systems, Research Article
Abstract: Vertical and torsional ocular misalignment can occur from mild traumatic brain injury or inner ear pathology, which may vary depending on head position. Here, we evaluate differences in a behavioral measure of binocular alignment in both upright and supine head position. Ocular perception of vertical and torsional alignment was measured using the torsional and vertical alignment nulling (TAN, VAN) task in N = 52 veterans with dizziness (N = 38 with traumatic brain injury), N = 41 civilians with vestibular schwannoma resection (UVD), and N = 33 healthy controls for both positions. The interquartile range within each group, regardless of head position, was greater for torsional compared to vertical misalignment. We use generalized estimating equations to compare average TAN (torsional) scores and VAN (vertical) scores between groups and test position. Compared to the healthy controls, TAN was significantly increased by + 0.4186° in veterans (P = 0.030) and by + 0.5747° in UVD (P = 0.010), but there was no difference with head position. For VAN, no difference was found between the three groups, but the misalignment did worsen by 0.0888° (P = 0.0070) as the head position moved from upright to supine. Head position had negligible effects on this behavioral measure of vertical and torsional binocular misalignment, and torsional misalignments were worse than controls in both veterans with dizziness and patients with vestibular nerve resection although neither reported torsional diplopia. Our data suggests that the tolerance for roll misalignment may be abnormally large in patients with dizziness. Alternatively, perceptual roll misalignments may be a manifest cause for dizziness, and therefore a useful proxy for distinguishing differences in putative otolith function in veterans with dizziness.
Published: 2022

49. Evidence of a decrease in sales of antimicrobials of very high importance for humans in dairy herds after a new regulation restricting their use in Quebec, Canada

Author: Nikky Millar, Cécile Aenishaenslin, Hélène Lardé, Jean‐Philippe Roy, Christine Fourichon, David Francoz, Marie‐Ève Paradis, and Simon Dufour
Subjects: Canada, Dairying, Infectious Diseases, Anti-Infective Agents, General Veterinary, General Immunology and Microbiology, Epidemiology, Quebec, Public Health, Environmental and Occupational Health, Animals, Humans, Cattle, Anti-Bacterial Agents
Abstract: In the province of Quebec, Canada, a new regulation restricting usage of antimicrobials of very high importance for human health (Health Canada: category 1 antimicrobials) in production animals is effective since February 2019. The objective of this study was to estimate changes in AM sales in dairy herds after the implementation of the regulation. Therefore, invoice data were extracted from veterinary software, Vet-Expert, used by most dairy veterinarians in the province of Quebec, and antimicrobial quantities were transformed in Canadian defined course doses for cattle (DCDbovCA). The sum of antimicrobials sales monthly in each herd was estimated in DCDbovCA from June 2016 to May 2020. To evaluate the herd-level change in AM sales and the impact of different factors, the number of DCDbovCA by herd from June 2017 to May 2018 (pre-regulation period) were compared with those of June 2019 to May 2020 (post-regulation period). Total category 1 AM sales of 3,569 Quebec's herds went from a range of 14,258 to 21,528 DCDbovCA/month to a range of 1,494 to 4,707 DCDbovCA/month after the implementation of the new regulation. Moreover, using data from 3,337 herds, we estimated a mean (95% confidence interval) reduction in 19 DCDbovCA/herd-year (14.8, 24.2), while the pre-regulation herd-level category 1 AM sales was 26 DCDbovCA/herd-year. This reduction was achieved without evidence of an increase in other antimicrobials. Finally, the veterinary facility associated with the herd was an important determinant of the herd-level reduction in category 1 antimicrobials. This study was the first to quantify a significant reduction in category 1 AM sales following the implementation of a restrictive regulation in dairy production in Canada. These results demonstrate that such an approach is effective to reduce the sales of a specific category of antimicrobial in animal production.
Published: 2022

50. Elevated muscle sympathetic activity in former smokers with heart failure

Author: Anthony V. Incognito, Hisayoshi Murai, Takuto Hamaoka, Hiroyuki Sugimoto, Philip J. Millar, and Masayuki Takamura
Subjects: Heart Failure, Smokers, Endocrine and Autonomic Systems, Muscles, Humans, Neurology (clinical)
Published: 2022

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