3,762 results on '"A, Alland"'
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2. Quality, Usability, and Trust Challenges to Effective Data Use in the Deployment and Use of the Bangladesh Nutrition Information System Dashboard: Qualitative Study
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Berhaun Fesshaye, Shivani Pandya, Lena Kan, Anna Kalbarczyk, Kelsey Alland, SM Mustafizur Rahman, Md. Mofijul Islam Bulbul, Piyali Mustaphi, Muhammad Abu Bakr Siddique, Md. Imtiaz Alam Tanim, Mridul Chowdhury, Tajkia Rumman, and Alain B Labrique more...
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundEvidence-based decision-making is essential to improve public health benefits and resources, especially in low- and middle-income countries (LMICs), but the mechanisms of its implementation remain less straightforward. The availability of high-quality, reliable, and sufficient data in LMICs can be challenging due to issues such as a lack of human resource capacity and weak digital infrastructure, among others. Health information systems (HISs) have been critical for aggregating and integrating health-related data from different sources to support evidence-based decision-making. Nutrition information systems (NISs), which are nutrition-focused HISs, collect and report on nutrition-related indicators to improve issues related to malnutrition and food security—and can assist in improving populations’ nutritional statuses and the integration of nutrition programming into routine health services. Data visualization tools (DVTs) such as dashboards have been recommended to support evidence-based decision-making, leveraging data from HISs or NISs. The use of such DVTs to support decision-making has largely been unexplored within LMIC contexts. In Bangladesh, the Mukto dashboard was developed to display and visualize nutrition-related performance indicators at the national and subnational levels. However, despite this effort, the current use of nutrition data to guide priorities and decisions remains relatively nascent and underused. ObjectiveThe goal of this study is to better understand how Bangladesh’s NIS, including the Mukto dashboard, has been used and areas for improvement to facilitate its use for evidence-based decision-making toward ameliorating nutrition-related service delivery and the health status of communities in Bangladesh. MethodsPrimary data collection was conducted through qualitative semistructured interviews with key policy-level stakeholders (n=24). Key informants were identified through purposive sampling and were asked questions about the experiences and challenges with the NIS and related nutrition dashboards. ResultsMain themes such as trust, data usability, personal power, and data use for decision-making emerged from the data. Trust in both data collection and quality was lacking among many stakeholders. Poor data usability stemmed from unstandardized indicators, irregular data collection, and differences between rural and urban data. Insufficient personal power and staff training coupled with infrastructural challenges can negatively affect data at the input stage. While stakeholders understood and expressed the importance of evidence-based decision-making, ultimately, they noted that the data were not being used to their maximum potential. ConclusionsLeveraging DVTs can improve the use of data for evidence-based decision-making, but decision makers must trust that the data are believable, credible, timely, and responsive. The results support the significance of a tailored data ecosystem, which has not reached its full potential in Bangladesh. Recommendations to reach this potential include ensuring a clear intended user base and accountable stakeholders are present. Systems should also have the capacity to ensure data credibility and support ongoing personal power requirements. more...
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- 2024
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3. Prelacteal feeding is not associated with infant size at 3 months in rural Bangladesh: a prospective cohort study
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Hannah Tong, Andrew Thorne-Lyman, Amanda C. Palmer, Saijuddin Shaikh, Hasmot Ali, Ya Gao, Monica M. Pasqualino, Lee Wu, Kelsey Alland, Kerry Schulze, Keith P. West, Jr., Md Iqbal Hossain, and Alain B. Labrique more...
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Breastfeeding ,Neonatal health ,Infant development ,Prelacteal ,Early newborn food ,South Asia ,Pediatrics ,RJ1-570 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Early and exclusive breastfeeding may reduce neonatal and post-neonatal mortality in low-resource settings. However, prelacteal feeding (PLF), the practice of giving food or liquid before breastfeeding is established, is still a barrier to optimal breastfeeding practices in many South Asian countries. We used a prospective cohort study to assess the association between feeding non-breastmilk food or liquid in the first three days of life and infant size at 3–5 months of age. Methods The analysis used data from 3,332 mother-infant pairs enrolled in a randomized controlled trial in northwestern rural Bangladesh conducted from 2018 to 2019. Trained interviewers visited women in their households during pregnancy to collect sociodemographic data. Project staff were notified of a birth by telephone and interviewers visited the home within approximately three days and three months post-partum. At each visit, interviewers collected data on breastfeeding practices and anthropometric measures. Infant length and weight measurements were used to produce length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores. We used multiple linear regression to assess the association between anthropometric indices and PLF practices, controlling for household wealth, maternal age, weight, education, occupation, and infant age, sex, and neonatal sizes. Results The prevalence of PLF was 23%. Compared to infants who did not receive PLF, infants who received PLF may have a higher LAZ (Mean difference (MD) = 0.02 [95% CI: -0.04, 0.08]) score, a lower WLZ (MD=-0.06 [95% CI: -0.15, 0.03]) score, and a lower WAZ (MD=-0.02 [95% CI: -0.08, 0.05]) score at 3–5 months of age, but none of the differences were statistically significant. In the adjusted model, female sex, larger size during the neonatal period, higher maternal education, and wealthier households were associated with larger infant size. Conclusion PLF was a common practice in this setting. Although no association between PLF and infant growth was identified, we cannot ignore the potential harm posed by PLF. Future studies could assess infant size at an earlier time point, such as 1-month postpartum, or use longitudinal data to assess more subtle differences in growth trajectories with PLF. Trial registration ClinicalTrials.gov: NCT03683667 and NCT02909179. more...
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- 2024
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4. An Egg Intervention Improves Ponderal But Not Linear Growth Among Infants 6–12 mo of Age in Rural Bangladesh
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Pasqualino, Monica M, Shaikh, Saijuddin, Hossain, Md Iqbal, Islam, Md Tanvir, Ali, Hasmot, Haque, Rezwanul, Ayesha, Kaniz, Wu, Lee S-F, Dyer, Brian, Hasan, Khaled, Alland, Kelsey, Schulze, Kerry J, Johura, Fatema-Tuz, Alam, Munirul, West, Keith P, Jr., Ahmed, Tahmeed, Labrique, Alain B, and Palmer, Amanda C more...
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- 2024
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5. Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment
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Georghiou, Sophia B, Rodwell, Timothy C, Korobitsyn, Alexei, Abbadi, Said H, Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C, Chakravorty, Soumitesh, Claxton, Pauline M, Cirillo, Daniela M, Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M, Derendinger, Brigitta, Desmond, Edward P, de Steenwinkel, Jurriaan EM, Dheda, Keertan, Diacon, Andreas H, Dolinger, David L, Dooley, Kelly E, Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R, Fattorini, Lanfranco, Finci, Iris, Le Ray, Laure Fournier, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K, Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L, Kambli, Priti, Kaniga, Koné, Karunaratne, GHR Eranga, Sharma, Meenu Kaushal, Keller, Peter M, Kelly, Ellis C, Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F, Limberis, Jason, Lin, S-Y Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martinez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R, Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P, Merker, Matthias, Miotto, Paolo, Omar, Shaheed V, Otto-Knapp, Ralf, Palaci, Moisés, Gutiérrez, Juan José Palacios, Peacock, Sharon J, Peloquin, Charles A, Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E, Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C, Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R, Spitaleri, Andrea, and Streicher, Elizabeth more...
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Biodefense ,Antimicrobial Resistance ,Prevention ,Rare Diseases ,Emerging Infectious Diseases ,Tuberculosis ,Clinical Research ,Vaccine Related ,Orphan Drug ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Antitubercular Agents ,Drug Resistance ,Bacterial ,Drug Resistance ,Multiple ,Bacterial ,Humans ,Microbial Sensitivity Tests ,Mycobacterium tuberculosis ,Tuberculosis ,Multidrug-Resistant ,Antimycobacterial Susceptibility Testing Group ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance. https://bit.ly/3i43wb6 more...
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- 2022
6. An expanded RT-PCR melting temperature coding assay to rapidly identify all known SARS-CoV-2 variants and sub-variants of concern
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Padmapriya P. Banada, Raquel Green, Deanna Streck, Rohini Kurvathi, Robert Reiss, Sukalyani Banik, Naranjargal Daivaa, Ibsen Montalvan, Robert Jones, Salvatore A. E. Marras, Soumitesh Chakravorty, and David Alland more...
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Medicine ,Science - Abstract
Abstract The continued emergence of vaccine-resistant SARS-CoV-2 variants of concern (VOC) requires specific identification of each VOC as it arises. Here, we report an expanded version of our previously described sloppy molecular beacon (SMB) melting temperature (Tm) signature-based assay for VOCs, now modified to include detection of Delta (B.1.617.2) and Omicron (B.1.1.529) sub-variants. The SMB-VOC assay targets the signature codons 501, 484 and 452 in the SARS-CoV-2 spike protein which we show can specifically detect and differentiate all known VOCs including the Omicron subvariants (BA.1, BA.2, BA.2.12.1, BA.4/BA.5). The limit of detection (LOD) of the assay was 20, 22 and 36 genomic equivalents (GE) per reaction with the Delta, Omicron BA.1 and BA.2 respectively. Clinical validation of the 3-codon assay in the LC480 instrument showed the assay detected 94% (81/86) of the specimens as WT or VOCs and 6% (5/86) of the tests producing indeterminate results compared to sequencing. Sanger sequencing also failed for four samples. None of the specimens were incorrectly identified as WT or as a different VOC by our assay. Thus, excluding specimens with indeterminant results, the assay was 100% sensitive and 100% specific compared to Sanger sequencing for variant identification. This new assay concept can be easily expanded to add newer variants and can serve as a robust diagnostic tool for selecting appropriate monoclonal antibody therapy and rapid VOC surveillance. more...
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- 2023
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7. Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture for detection of Mycobacterium tuberculosis in symptomatic adults: a diagnostic accuracy study
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Xie, Yingda L, Eichberg, Christie, Hapeela, Nchimunya, Nakabugo, Elizabeth, Anyango, Irene, Arora, Kiranjot, Korte, Jeffrey E, Odero, Ronald, van Heerden, Judi, Zemanay, Widaad, Kennedy, Samuel, Nabeta, Pamela, Hanif, Mahmud, Rodrigues, Camilla, Skrahina, Alena, Stevens, Wendy, Dietze, Reynaldo, Liu, Xin, Ellner, Jerrold J, Alland, David, Joloba, Moses L, Schumacher, Samuel G, McCarthy, Kimberly D, Nakiyingi, Lydia, and Dorman, Susan E more...
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- 2024
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8. Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise
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Alland, David, Behr, Marcel A, Beko, Busisiwe B, Burhan, Erlina, Churchyard, Gavin, Cobelens, Frank, Denholm, Justin T, Dinkele, Ryan, Ellner, Jerrold J, Fatima, Razia, Haigh, Kate A, Hatherill, Mark, Horton, Katherine C, Kendall, Emily A, Khan, Palwasha Y, MacPherson, Peter, Malherbe, Stephanus T, Mave, Vidya, Mendelsohn, Simon C, Musvosvi, Munyaradzi, Nemes, Elisa, Penn-Nicholson, Adam, Ramamurthy, Dharanidharan, Rangaka, Molebogeng X, Sahu, Suvanand, Schwalb, Alvaro, Shah, Divya K, Sheerin, Dylan, Simon, Donald, Steyn, Adrie J C, Thu Anh, Nguyen, Walzl, Gerhard, Weller, Charlotte L, Williams, Caroline ML, Wong, Emily B, Wood, Robin, Xie, Yingda L, Yi, Siyan, Coussens, Anna K, Zaidi, Syed M A, Allwood, Brian W, Dewan, Puneet K, Gray, Glenda, Kohli, Mikashmi, Kredo, Tamara, Marais, Ben J, Marks, Guy B, Martinez, Leo, Ruhwald, Morten, Scriba, Thomas J, Seddon, James A, Tisile, Phumeza, Warner, Digby F, Wilkinson, Robert J, Esmail, Hanif, and Houben, Rein M G J more...
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- 2024
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9. An expanded RT-PCR melting temperature coding assay to rapidly identify all known SARS-CoV-2 variants and sub-variants of concern
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Banada, Padmapriya P., Green, Raquel, Streck, Deanna, Kurvathi, Rohini, Reiss, Robert, Banik, Sukalyani, Daivaa, Naranjargal, Montalvan, Ibsen, Jones, Robert, Marras, Salvatore A. E., Chakravorty, Soumitesh, and Alland, David more...
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- 2023
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10. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies
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Topp, Max, Dlugosz-Danecka, Monika, Skotnicki, Aleksander B., Salogub, Galina, Viardot, Andreas, Klein, Andreas K., Hess, Georg, Michel, Christian S., Grosicki, Sebastian, Gural, Alex, Schwarz, Sylvia E., Pietzko, Kerstin, Gärtner, Ulrike, Strassz, András, Alland, Leila, and Mayer, Jiri more...
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- 2023
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11. Accuracy of a smartphone application for blood pressure estimation in Bangladesh, South Africa, and Tanzania
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Festo, Charles, Vannevel, Valerie, Ali, Hasmot, Tamrat, Tigest, Mollel, Getrud J., Hlongwane, Tsakane, Fahmida, Kaniz A., Alland, Kelsey, Barreix, María, Mehrtash, Hedieh, Silva, Ronaldo, Thwin, Soe Soe, Mehl, Garrett, Labrique, Alain B., Masanja, Honorati, and Tunçalp, Ӧzge more...
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- 2023
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12. Considering a Marketing Degree? Student Perceptions of General versus Specialized Majors
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Atkin, JoAnn L., Bowie, Anthony Alland, Cowley, Scott, Eckert, James A., Ferrin, Bruce G., Harrison, Robert L., Lancendorfer, Karen M., Luqmani, Mushtaq, Luqmani, Zahida, Leingpibul, Thaweephan, Mumuni, Alhassan G., O'Reilly, Kelley, Quraeshi, Zahir A., Samples, Robert G., Veeck, Ann, Xie, Hu, and Zondag, Marcellis M. more...
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Many business colleges offer specialized marketing majors in addition to the general marketing major. Given the extra resources needed to maintain multiple majors, in a time when higher education budgets are being strained, a need exists to understand how students make choices among these majors and what students perceive to be the advantages of general marketing majors versus specialized marketing majors. Using social cognitive theory, we examine how students make selections among choices in marketing-related majors, focusing on influence and compatibility factors. We surveyed 608 marketing majors representing one general and five specialized marketing majors. The findings indicate that, compared with general marketing majors, students' choice of a specialized major is significantly more likely to be influenced by faculty and other students in the major. Also, the results show that students rate specialized majors better than a general marketing major in terms of self-efficacy, culture, and professional fit. On the other hand, students rate the general marketing major better than specialized majors in flexibility. These results have implications for supporting the priorities of students in both general and specialized majors. more...
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- 2022
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13. Accuracy of a smartphone application for blood pressure estimation in Bangladesh, South Africa, and Tanzania
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Charles Festo, Valerie Vannevel, Hasmot Ali, Tigest Tamrat, Getrud J. Mollel, Tsakane Hlongwane, Kaniz A. Fahmida, Kelsey Alland, María Barreix, Hedieh Mehrtash, Ronaldo Silva, Soe Soe Thwin, Garrett Mehl, Alain B. Labrique, Honorati Masanja, and Ӧzge Tunçalp more...
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Undetected and unmonitored hypertension carries substantial mortality and morbidity, especially during pregnancy. We assessed the accuracy of OptiBPTM, a smartphone application for estimating blood pressure (BP), across diverse settings. The study was conducted in community settings: Gaibandha, Bangladesh and Ifakara, Tanzania for general populations, and Kalafong Provincial Tertiary Hospital, South Africa for pregnant populations. Based on guidance from the International Organization for Standardization (ISO) 81,060–2:2018 for non-invasive BP devices and global consensus statement, we compared BP measurements taken by two independent trained nurses on a standard auscultatory cuff to the BP measurements taken by a research version of OptiBPTM called CamBP. For ISO criterion 1, the mean error was 0.5 ± 5.8 mm Hg for the systolic blood pressure (SBP) and 0.1 ± 3.9 mmHg for the diastolic blood pressure (DBP) in South Africa; 0.8 ± 7.0 mmHg for the SBP and −0.4 ± 4.0 mmHg for the DBP in Tanzania; 3.3 ± 7.4 mmHg for the SBP and −0.4 ± 4.3 mmHg for the DBP in Bangladesh. For ISO criterion 2, the average standard deviation of the mean error per subject was 4.9 mmHg for the SBP and 3.4 mmHg for the DBP in South Africa; 6.3 mmHg for the SBP and 3.6 mmHg for the DBP in Tanzania; 6.4 mmHg for the SBP and 3.8 mmHg for the DBP in Bangladesh. OptiBPTM demonstrated accuracy against ISO standards in study populations, including pregnant populations, except in Bangladesh for SBP (criterion 2). Further research is needed to improve performance across different populations and integration within health systems. more...
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- 2023
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14. Author Correction: Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase
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Ezewudo, Matthew, Borens, Amanda, Chiner-Oms, Álvaro, Miotto, Paolo, Chindelevitch, Leonid, Starks, Angela M, Hanna, Debra, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Kohl, Thomas Andreas, Warren, Robin M, Crook, Derrick, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, McNerney, Ruth, Cirillo, Daniela M, Schito, Marco, Rodwell, Timothy C, and Posey, James more...
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Microbiology ,Biological Sciences ,Infection ,Good Health and Well Being - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
15. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies
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Max Topp, Monika Dlugosz-Danecka, Aleksander B. Skotnicki, Galina Salogub, Andreas Viardot, Andreas K. Klein, Georg Hess, Christian S. Michel, Sebastian Grosicki, Alex Gural, Sylvia E. Schwarz, Kerstin Pietzko, Ulrike Gärtner, András Strassz, Leila Alland, and Jiri Mayer more...
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Non-Hodgkin lymphoma ,Acute lymphoblastic leukaemia ,AFM11 ,Neurotoxicity ,T-cell engager ,Medicine (General) ,R5-920 - Abstract
Abstract Background The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin’s lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells. Methods Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion. Results In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination. Conclusions AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated. Trial registration NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016. more...
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- 2023
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16. Digitalization of routine health information systems: Bangladesh, Indonesia, Pakistan/Numerisation des systemes d'information sanitaire habituels au Bangladesh, en Indonesie et au Pakistan/Digitalizacion de los sistemas habituales de informacion sanitaria en Bangladesh, Indonesia y Pakistan
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Tamrat, Tigest, Chandir, Subhash, Alland, Kelsey, Pedrana, Alisa, Shah, Mubarak Talghoon, Footitt, Carolyn, Snyder, Jennifer, Ratanaprayul, Natschja, Siddiqi, Danya Arif, Nazneen, Numera, Syah, Inraini Fitria, Wong, Roger, Lubell-Doughtie, Peter, Utami, Annisa Dwi, Anwar, Khaerul, Ali, Hasmot, Labrique, Alain B., Say, Lale, Shankar, Anuraj H., and Mehl, Garrett Livingston more...
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Mobile devices -- Usage ,Vaccination -- Usage ,Usability testing -- Usage ,Medical informatics -- Usage ,Information storage and retrieval -- Usage ,Health ,World Health Organization - Abstract
Objective To describe a systematic process of transforming paper registers into a digital system optimized to enhance service provision and fulfil reporting requirements. Methods We designed a formative study around primary health workers providing reproductive, maternal, newborn and child health services in three countries in Bangladesh, Indonesia and Pakistan. The study ran from November 2014 to June 2018. We developed a prototype digital application after conducting a needs assessment of health workers' responsibilities, workflows, routine data requirements and service delivery needs. Methods included desk reviews, focus group discussions, in-depth interviews; data mapping of paper registers; observations of health workers; co-design workshops with health workers; and usability testing. Finally, we conducted an observational feasibility assessment to monitor uptake of the application. Findings Researchers reviewed a total of 17 paper registers across the sites, which we transformed into seven modules within a digital application running on mobile devices. Modules corresponded to the services provided, including household enumeration, antenatal care, family planning, immunization, nutrition and child health. A total of 65 health workers used the modules during the feasibility assessment, and average weekly form submissions ranged from 8 to 234, depending on the health worker and their responsibilities. We also observed variability in the use of modules, requiring consistent monitoring support for health workers. Conclusion Lessons learnt from this study shaped key global initiatives and resulted in a software global good. The deployment of digital systems requires well-designed applications, change management and strengthening human resources to realize and sustain health system gains. Objectif Decrire un processus methodique de transformation des registres papier en systeme numerique optimise, en vue d'ameliorer la fourniture de services et de remplir les exigences relatives a l'etablissement de rapports. Methodes Nous avons concu une etude formative consacree aux professionnels des soins primaires proposant des services de sante reproductive et maternelle, de sante des nouveau-nes et de sante infantile dans trois pays: le Bangladesh, l'Indonesie et le Pakistan. Cette etude a ete menee entre novembre 2014 et juin 2018. Nous avons mis au point un prototype d'application numerique apres avoir evalue les besoins des soignants, leurs responsabilites, leur charge de travail, les donnees necessaires a leurs activites quotidiennes et les imperatifs lies a leurs prestations de service. Parmi les methodes employees figuraient des examens documentaires, des discussions de groupes, des entretiens approfondis; une cartographie des donnees fondee sur les registres papier; une observation des professionnels de la sante; des ateliers de cocreation avec les soignants; et enfin, des tests d'utilisabilite. Pour terminer, nous avons effectue une analyse de faisabilite observationnelle afin de mesurer le taux d'adhesion a l'application. Resultats Les chercheurs ont passe au crible un total de 17 registres papier sur l'ensemble des sites, que nous avons transformes en sept modules repris dans une application numerique compatible avec les appareils mobiles. Ces modules correspondaient aux services proposes, dont le recensement des menages, les soins prenatals, la planification familiale, la vaccination, la nutrition et la sante infantile. Au total, 65 soignants ont utilise les modules au cours de l'analyse de faisabilite et le nombre moyen de formulaires soumis chaque semaine etait compris entre 8 et 234, en fonction du soignant et de ses responsabilites. Nous avons egalement observe des variations dans l'utilisation des modules, ce qui montre la necessite d'assurer un suivi permanent aupres des professionnels de la sante. Conclusion Les lecons tirees de cette etude ont permis de faconner des initiatives internationales majeures et d'elaborer un logiciel d'interet mondial. Le deploiement de dispositifs numeriques requiert des applications bien pensees, une bonne gestion du changement et un renforcement des ressources humaines afin d'obtenir et de preserver les avantages pour le systeme de sante. Objetivo Describir un proceso sistematico que permita transformar los registros en papel en un sistema digital optimizado para mejorar la prestacion de servicios y cumplir con los requisitos de informacion. Metodos Se diseno un estudio formativo en torno a los profesionales de la salud primaria que prestan servicios de salud reproductiva, materna, neonatal e infantil en tres paises: de Bangladesh, Indonesia y Pakistan. El estudio se realizodesarrollo entre noviembre de 2014 y junio de 2018. Se desarrollo un prototipo de aplicacion digital despues de realizar una evaluacion sobre las necesidades de las responsabilidades de los profesionales sanitarios, los flujos de trabajo, los requisitos de datos rutinarios y las necesidades de prestacion de servicios. Los metodos incluyeron revisiones de documentos, grupos de discusion, entrevistas en profundidad; mapeo de datos de los registros en papel; observaciones de los profesionales sanitarios; talleres de codiseno con los profesionales sanitarios; y pruebas de usabilidad. Por ultimo, se llevo a cabo una evaluacion de viabilidad observacional para supervisar la aceptacion de la aplicacion. Resultados Los investigadores revisaron un total de 17 registros en papel en todos los sitios, que se adaptaron a siete modulos dentro de una aplicacion digital que funcionaba en dispositivos moviles. Los modulos correspondian a los servicios prestados, como la enumeracion de los hogares, la atencion prenatal, la planificacion familiar, la inmunizacion, la nutricion y la salud infantil. Un total de 65 profesionales sanitarios utilizaron los modulos durante la evaluacion de viabilidad, y la media de envios de formularios semanales oscilo entre 8 y 234, dependiendo del profesional sanitario y de sus responsabilidades. Tambien se observo una variabilidad en el uso de los modulos, lo que requirio un apoyo de seguimiento constante por parte de los profesionales sanitarios. Conclusion Las lecciones aprendidas de este estudio dieron forma a iniciativas globales clave y permitieron crear un programa informatico de interes mundial. El despliegue de los sistemas digitales requiere aplicaciones bien disenadas, la gestion del cambio y el fortalecimiento de los recursos humanos para realizar y mantener los beneficios del sistema sanitario., Introduction Global agencies advocate for the use of information and communication technologies to accelerate progress on priorities, such as the sustainable development goals, the Roadmap for Measurement and Accountability, and [...] more...
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- 2022
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17. Diagnostic accuracy of the NOVA Tuberculosis Total Antibody Rapid test for detection of pulmonary tuberculosis and infection with Mycobacterium tuberculosis
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Nsubuga, Gideon, Kennedy, Samuel, Rani, Yasha, Hafiz, Zibran, Kim, Soyeon, Ruhwald, Morten, Alland, David, Ellner, Jerrold, Joloba, Moses, Dorman, Susan E., Penn-Nicholson, Adam, and Nakiyingi, Lydia
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- 2023
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18. Structural and functional studies of scorpine: A channel blocker and cytolytic peptide
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López-Giraldo, Estefanía, Carrillo, Elisa, Titaux-Delgado, Gustavo, Cano-Sánchez, Patricia, Colorado, Alland, Possani, Lourival D., and Río-Portilla, Federico del
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- 2023
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19. A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome
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Poonam Chitale, Alexander D. Lemenze, Emily C. Fogarty, Avi Shah, Courtney Grady, Aubrey R. Odom-Mabey, W. Evan Johnson, Jason H. Yang, A. Murat Eren, Roland Brosch, Pradeep Kumar, and David Alland
- Subjects
Science - Abstract
H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is the reference sequence for this pathogen. Here, Chitale et al. present a bioinformatic pipeline for accurate assembly of bacterial genome sequences, and use it to provide important updates to the M. tuberculosis reference genome. more...
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- 2022
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20. Diagnostic accuracy of the NOVA Tuberculosis Total Antibody Rapid test for detection of pulmonary tuberculosis and infection with Mycobacterium tuberculosis
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Gideon Nsubuga, Samuel Kennedy, Yasha Rani, Zibran Hafiz, Soyeon Kim, Morten Ruhwald, David Alland, Jerrold Ellner, Moses Joloba, Susan E. Dorman, Adam Penn-Nicholson, and Lydia Nakiyingi
- Subjects
Tuberculosis ,Mycobacteria ,Diagnostic accuracy ,Specificity ,Sensitivity ,Lateral flow ,Diseases of the respiratory system ,RC705-779 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background: The NOVA Tuberculosis Total Antibody Rapid Test is a commercially available lateral flow serological assay that is intended to be used as an aid in the diagnosis of tuberculosis. We conducted a study to estimate diagnostic accuracy of this assay for diagnosis of active pulmonary tuberculosis disease and for detection of M. tuberculosis infection. Methods: This study used existing frozen plasma specimens that had been obtained previously from consenting HIV-negative adults in Cambodia, South Africa, and Vietnam whose tuberculosis status was rigorously characterized using sputum mycobacterial cultures and blood interferon gamma release assay. The investigational assay was performed in a single laboratory by laboratory staff specifically trained to conduct the assays according to the manufacturer’s procedures. In addition, intensity of the test band was subjectively assessed. Results: Plasma specimens from 150 participants were tested. All testing attempts yielded a determinate result of either positive or negative. For diagnosis of active pulmonary tuberculosis disease, test sensitivity and specificity were 40.0 % (20/50, 95 % confidence interval [CI] 27.6 % to 53.8 %) and 85.0 % (95 % CI 76.7 % to 90.7 %), respectively. For detection of M. tuberculosis infection, test sensitivity and specificity were 28.0 % (95 % CI 20.5 % to 37.2 %) and 86.0 % (95 % CI 73.8 % to 93.0 %), respectively. Among the 35 positive tests, no statistically significant band intensity trend was found across participant groups (p = 0.17). Conclusion: Study findings do not support a role for the NOVA Tuberculosis Test in current tuberculosis diagnostic algorithms. more...
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- 2023
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21. Development of a novel human CD147 knock-in NSG mouse model to test SARS-CoV-2 viral infection
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Saiaditya Badeti, Qingkui Jiang, Alireza Naghizadeh, Hsiang-chi Tseng, Yuri Bushkin, Salvatore A. E. Marras, Annuurun Nisa, Sanjay Tyagi, Fei Chen, Peter Romanienko, Ghassan Yehia, Deborah Evans, Moises Lopez-Gonzalez, David Alland, Riccardo Russo, William Gause, Lanbo Shi, and Dongfang Liu more...
- Subjects
CD147 ,Basigin ,BSG ,hCD147KI ,NSG ,SARS-CoV-2 ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background An animal model that can mimic the SARS-CoV-2 infection in humans is critical to understanding the rapidly evolving SARS-CoV-2 virus and for development of prophylactic and therapeutic strategies to combat emerging mutants. Studies show that the spike proteins of SARS-CoV and SARS-CoV-2 bind to human angiotensin-converting enzyme 2 (hACE2, a well-recognized, functional receptor for SARS-CoV and SARS-CoV-2) to mediate viral entry. Several hACE2 transgenic (hACE2Tg) mouse models are being widely used, which are clearly invaluable. However, the hACE2Tg mouse model cannot fully explain: (1) low expression of ACE2 observed in human lung and heart, but lung or heart failure occurs frequently in severe COVID-19 patients; (2) low expression of ACE2 on immune cells, but lymphocytopenia occurs frequently in COVID-19 patients; and (3) hACE2Tg mice do not mimic the natural course of SARS-CoV-2 infection in humans. Moreover, one of most outstanding features of coronavirus infection is the diversity of receptor usage, which includes the newly proposed human CD147 (hCD147) as a possible co-receptor for SARS-CoV-2 entry. It is still debatable whether CD147 can serve as a functional receptor for SARS-CoV-2 infection or entry. Results Here we successfully generated a hCD147 knock-in mouse model (hCD147KI) in the NOD-scid IL2Rgammanull (NSG) background. In this hCD147KI-NSG mouse model, the hCD147 genetic sequence was placed downstream of the endogenous mouse promoter for mouse CD147 (mCD147), which creates an in vivo model that may better recapitulate physiological expression of hCD147 proteins at the molecular level compared to the existing and well-studied K18-hACE2-B6 (JAX) model. In addition, the hCD147KI-NSG mouse model allows further study of SARS-CoV-2 in the immunodeficiency condition which may assist our understanding of this virus in the context of high-risk populations in immunosuppressed states. Our data show (1) the human CD147 protein is expressed in various organs (including bronchiolar epithelial cells) in hCD147KI-NSG mice by immunohistochemical staining and flow cytometry; (2) hCD147KI-NSG mice are marginally sensitive to SARS-CoV-2 infection compared to WT-NSG littermates characterized by increased viral copies by qRT-PCR and moderate body weight decline compared to baseline; (3) a significant increase in leukocytes in the lungs of hCD147KI-NSG mice, compared to infected WT-NSG mice. Conclusions hCD147KI-NSG mice are more sensitive to COVID-19 infection compared to WT-NSG mice. The hCD147KI-NSG mouse model can serve as an additional animal model for further interrogation whether CD147 serve as an independent functional receptor or accessory receptor for SARS-CoV-2 entry and immune responses. more...
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- 2022
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22. RT-PCR negative COVID-19
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Heta Parmar, Margaret Montovano, Padmapriya Banada, Sri Ram Pentakota, Stephanie Shiau, Zhongjie Ma, Kaheerman Saibire, Abby Chopoorian, Michael O’Shaughnessy, Mitchell Hirsch, Priyanshi Jain, Gaiane Demirdjian, Magali Karagueuzian, Thomas Robin, Michael Salvati, Bhavana Patel, David Alland, and Yingda L. Xie more...
- Subjects
COVID-19 ,SARS-CoV-2 ,Suspects ,RT-PCR ,Diagnosis ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background COVID-19 is a multi-system infection with emerging evidence-based antiviral and anti-inflammatory therapies to improve disease prognosis. However, a subset of patients with COVID-19 signs and symptoms have repeatedly negative RT-PCR tests, leading to treatment hesitancy. We used comparative serology early in the COVID-19 pandemic when background seroprevalence was low to estimate the likelihood of COVID-19 infection among RT-PCR negative patients with clinical signs and/or symptoms compatible with COVID-19. Methods Between April and October 2020, we conducted serologic testing of patients with (i) signs and symptoms of COVID-19 who were repeatedly negative by RT-PCR (‘Probables’; N = 20), (ii) signs and symptoms of COVID-19 but with a potential alternative diagnosis (‘Suspects’; N = 15), (iii) no signs and symptoms of COVID-19 (‘Non-suspects’; N = 43), (iv) RT-PCR confirmed COVID-19 patients (N = 40), and (v) pre-pandemic samples (N = 55). Results Probables had similar seropositivity and levels of IgG and IgM antibodies as propensity-score matched RT-PCR confirmed COVID-19 patients (60.0% vs 80.0% for IgG, p-value = 0.13; 50.0% vs 72.5% for IgM, p-value = 0.10), but multi-fold higher seropositivity rates than Suspects and matched Non-suspects (60.0% vs 13.3% and 11.6% for IgG; 50.0% vs 0% and 4.7% for IgM respectively; p-values more...
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- 2022
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23. Persistence of SARS-CoV-2 in saliva: Implications for late-stage diagnosis and infectious duration.
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Abby Chopoorian, Padmapriya Banada, Robert Reiss, David Elson, Samuel Desind, Claire Park, Sukalyani Banik, Emily Hennig, Aanchal Wats, Austin Togba, Abraham Wei, Naranjargal Daivaa, Laura Palo, Mitchell Hirsch, Carter Campbell, Pooja Saiganesh, David Alland, and Yingda L Xie more...
- Subjects
Medicine ,Science - Abstract
Saliva has been a COVID-19 diagnostic specimen of interest due to its simple collection, scalability, and yield. Yet COVID-19 testing and estimates of the infectious period remain largely based on nasopharyngeal and nasal swabs. We sought to evaluate whether saliva testing captured prolonged presence of SARS-CoV-2 and potential infectiousness later in the disease course. We conducted an observational study of symptomatic COVID-19 patients at University Hospital in Newark, NJ. Paired saliva and nasal specimens from 96 patients were analyzed, including longitudinal analysis of paired observations from 28 of these patients who had multiple time-points. Saliva detected significantly more cases of COVID-19 beyond 5 days (86.1% [99/115] saliva vs 48.7% [56/115] nasal, p-value < 0.001), 9 days (79.4% [50/63] saliva vs 36.5% [23/63] nasal, p-value < 0.001) and 14 days (71.4% [20/28] saliva vs 32.1% [9/28] nasal, p-value = 0.010) of symptoms. Additionally, saliva yielded lower cycle thresholds across all time periods, indicative of higher viral loads in saliva. In the longitudinal analysis, a log-rank analysis indicated that the survival curve for saliva was significantly different from the curve for nasal swabs (p more...
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- 2023
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24. Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase
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Ezewudo, Matthew, Borens, Amanda, Chiner-Oms, Álvaro, Miotto, Paolo, Chindelevitch, Leonid, Starks, Angela M, Hanna, Debra, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Kohl, Thomas Andreas, Warren, Robin M, Crook, Derrick, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, McNerney, Ruth, Cirillo, Daniela M, Schito, Marco, Rodwell, Timothy C, and Posey, James more...
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Microbiology ,Clinical Sciences ,Human Genome ,Tuberculosis ,Antimicrobial Resistance ,Rare Diseases ,Biotechnology ,Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Antitubercular Agents ,Bacterial Proteins ,Drug Resistance ,Multiple ,Bacterial ,Genome ,Bacterial ,Genotype ,Humans ,Knowledge Bases ,Mutation ,Mycobacterium tuberculosis ,Polymorphism ,Single Nucleotide ,Sequence Analysis ,DNA ,Tuberculosis ,Multidrug-Resistant ,Whole Genome Sequencing - Abstract
Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis. more...
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- 2018
25. RT-PCR negative COVID-19
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Parmar, Heta, Montovano, Margaret, Banada, Padmapriya, Pentakota, Sri Ram, Shiau, Stephanie, Ma, Zhongjie, Saibire, Kaheerman, Chopoorian, Abby, O’Shaughnessy, Michael, Hirsch, Mitchell, Jain, Priyanshi, Demirdjian, Gaiane, Karagueuzian, Magali, Robin, Thomas, Salvati, Michael, Patel, Bhavana, Alland, David, and Xie, Yingda L. more...
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- 2022
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26. Development of a novel human CD147 knock-in NSG mouse model to test SARS-CoV-2 viral infection
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Badeti, Saiaditya, Jiang, Qingkui, Naghizadeh, Alireza, Tseng, Hsiang-chi, Bushkin, Yuri, Marras, Salvatore A. E., Nisa, Annuurun, Tyagi, Sanjay, Chen, Fei, Romanienko, Peter, Yehia, Ghassan, Evans, Deborah, Lopez-Gonzalez, Moises, Alland, David, Russo, Riccardo, Gause, William, Shi, Lanbo, and Liu, Dongfang more...
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- 2022
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27. Author Correction: A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome
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Chitale, Poonam, Lemenze, Alexander D., Fogarty, Emily C., Shah, Avi, Grady, Courtney, Odom-Mabey, Aubrey R., Johnson, W. Evan, Yang, Jason H., Eren, A. Murat, Brosch, Roland, Kumar, Pradeep, and Alland, David more...
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- 2022
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28. A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome
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Chitale, Poonam, Lemenze, Alexander D., Fogarty, Emily C., Shah, Avi, Grady, Courtney, Odom-Mabey, Aubrey R., Johnson, W. Evan, Yang, Jason H., Eren, A. Murat, Brosch, Roland, Kumar, Pradeep, and Alland, David more...
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- 2022
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29. REPLY TO VARGAS AND FARHAT : Mycobacterium tuberculosis glpK mutants in human tuberculosis
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Safi, Hassan, Sherman, David R., Dick, Thomas, and Alland, David
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- 2020
30. Tips for managing 4 common soft-tissue finger and thumb injuries
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Nicholson, Caitlin A. and Alland, Jeremy A.
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Fingers -- Injuries ,Health - Abstract
After examination and, in some cases, imaging, most of these injuries can be managed conservatively with splinting or injection. Some cases require prompt surgical referral. Finger injuries are often seen [...] more...
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- 2022
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31. Pattern avoidance and fiber bundle structures on Schubert varieties
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Alland, Timothy and Richmond, Edward
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Mathematics - Combinatorics ,14M15, 22E40, 20F55, 05A05, 05E05 - Abstract
We give a permutation pattern avoidance criteria for determining when the projection map from the flag variety to a Grassmannian induces a fiber bundle structure on a Schubert variety. In particular, we introduce the notion of a split pattern and show that a Schubert variety has such a fiber bundle structure if and only if the corresponding permutation avoids the split patterns 3|12 and 23|1. Continuing, we show that a Schubert variety is an iterated fiber bundle of Grassmannian Schubert varieties if and only if the corresponding permutation avoids (non-split) patterns 3412, 52341, and 635241. This extends a combined result of Lakshmibai-Sandhya, Ryan, and Wolper who prove that Schubert varieties whose permutation avoids the "smooth" patterns 3412 and 4231 are iterated fiber bundles of smooth Grassmannian Schubert varieties., Comment: 16 pages and 9 Figures more...
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- 2016
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32. Origin and Dynamics of Mycobacterium tuberculosis Subpopulations That Predictably Generate Drug Tolerance and Resistance
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Jees Sebastian, Anooja Thomas, Carly Levine, Riju Shrestha, Shawn Levy, Hassan Safi, Sri Ram Pentakota, Pradeep Kumar, and David Alland
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Mycobacterium tuberculosis ,antibiotic tolerance ,antibiotic resistance ,chromosomal barcoding ,Microbiology ,QR1-502 - Abstract
ABSTRACT Initial responses to tuberculosis treatment are poor predictors of final therapeutic outcomes in drug-susceptible disease, suggesting that treatment success depends on features that are hidden within a small minority of the overall infecting Mycobacterium tuberculosis population. We developed a multitranswell robotic system to perform numerous parallel cultures of genetically barcoded M. tuberculosis exposed to steady-state concentrations of rifampicin to uncover these difficult-to-eliminate minority populations. We found that tolerance emerged repeatedly from at least two subpopulations of barcoded cells, namely, one that could not grow on solid agar media and a second that could form colonies, but whose kill curves diverged from the general bacterial population within 4 and 16 days of drug exposure, respectively. These tolerant subpopulations reproducibly passed through a phase characterized by multiple unfixed resistance mutations followed by emergent drug resistance in some cultures. Barcodes associated with drug resistance identified an especially privileged subpopulation that was rarely eliminated despite 20 days of drug treatment even in cultures that did not contain any drug-resistant mutants. The association of this evolutionary scenario with a defined subset of barcodes across multiple independent cultures suggested a transiently heritable phenotype, and indeed, glpK phase variation mutants were associated with up to 16% of the resistant cultures. Drug tolerance and resistance were eliminated in a ΔruvA mutant, consistent with the importance of bacterial stress responses. This work provides a window into the origin and dynamics of bacterial drug-tolerant subpopulations whose elimination may be critical for developing rapid and resistance-free cures. IMPORTANCE Tuberculosis is unusual among bacterial diseases in that treatments which can rapidly resolve symptoms do not predictably lead to a durable cure unless treatment is continued for months after all clinical and microbiological signs of disease have been eradicated. Using a novel steady-state antibiotic exposure system combined with chromosomal barcoding, we identified small hidden Mycobacterium tuberculosis subpopulations that repeatedly enter a state of drug tolerance with a predisposition to develop fixed drug resistance after first developing a cloud of unfixed resistance mutations. The existence of these difficult-to-eradicate subpopulations may explain the need for extended treatment regimen for tuberculosis. Their identification provides opportunities to test genetic and therapeutic approaches that may result in shorter and more effective TB treatments. more...
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- 2022
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33. Reversible gene silencing through frameshift indels and frameshift scars provide adaptive plasticity for Mycobacterium tuberculosis
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Aditi Gupta and David Alland
- Subjects
Science - Abstract
Bacterial adaptation through frame-shifting insertions and deletions (indels) could be reversed by secondary introduction of a frame-restoring indel. Here, the authors develop ScarTrek, a program that scans genomic data for different indels, and analyze 5977 clinical M. tuberculosis isolates for indel frequency. more...
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- 2021
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34. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
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Miotto, Paolo, Tessema, Belay, Tagliani, Elisa, Chindelevitch, Leonid, Starks, Angela M, Emerson, Claudia, Hanna, Debra, Kim, Peter S, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Denkinger, Claudia M, Fleming, Joy, Warren, Robin M, Crook, Derrick, Posey, James, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Murray, Megan, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, Ranganathan, Uma Devi K, McNerney, Ruth, Ezewudo, Matthew, Cirillo, Daniela M, Schito, Marco, Köser, Claudio U, and Rodwell, Timothy C more...
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Tuberculosis ,HIV/AIDS ,Antimicrobial Resistance ,Genetics ,Rare Diseases ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Antitubercular Agents ,Bacterial Proteins ,DNA ,Bacterial ,Data Interpretation ,Statistical ,Drug Resistance ,Multiple ,Bacterial ,Genotype ,Humans ,Microbial Sensitivity Tests ,Mutation ,Mycobacterium tuberculosis ,Phenotype ,Sequence Analysis ,DNA ,Systematic Reviews as Topic ,Tuberculosis ,Multidrug-Resistant ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis. more...
- Published
- 2017
35. Decontaminating N95 respirators during the COVID-19 pandemic: simple and practical approaches to increase decontamination capacity, speed, safety and ease of use
- Author
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Russo, R., Levine, C., Grady, C., Peixoto, B., McCormick-Ell, J., Block, T., Gresko, A., Delmas, G., Chitale, P., Frees, A., Ruiz, A., and Alland, D.
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- 2021
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36. Use, re-use or discard? Quantitatively defined variance in the functional integrity of N95 respirators following vaporized hydrogen peroxide decontamination during the COVID-19 pandemic
- Author
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Levine, C., Grady, C., Block, T., Hurley, H., Russo, R., Peixoto, B., Frees, A., Ruiz, A., and Alland, D.
- Published
- 2021
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37. Dual mobility versus conventional total hip arthroplasty in femoral neck fractures (DISTINCT): protocol for a registry-nested, open-label, cluster-randomised crossover trial
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Ian A Harris, Jacqueline Close, Richard S de Steiger, Sam Adie, Steven E Graves, Michelle Lorimer, Thu-Lan Kelly, Justine M Naylor, Tamara Hooper, Margaret Rogers, Peter L Lewis, John E Farey, Tania Alland, and Adriane M Lewin more...
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Medicine - Abstract
Introduction Hip fractures treated with total hip arthroplasty (THA) are at high risk of prosthesis instability, and dislocation is the most common indication for revision surgery. This study aims to determine whether dual mobility THA implants reduce the risk of dislocation compared with conventional THA in patients with hip fracture suitable to be treated with THA.Methods and analysis This is a cluster-randomised, crossover, open-label trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will comprise hospitals that perform at least 12 THAs for hip fracture per annum. All adults age ≥50 years who meet the Australian and New Zealand Hip Fracture Registry guidelines for THA will be included. The intervention will be dual mobility THA and the comparator will be conventional THA. Each hospital will be allocated to two consecutive periods, one of dual mobility THA and the other of conventional THA in random order, aiming for an average of 16 patients eligible for the primary analysis per group (32 total per site), allowing different recruitment totals between sites. Data will be collected through the AOANJRR and linked with patient-level discharge data acquired through government agencies. The primary outcome is dislocation within 1 year. Secondary outcomes include revision surgery for dislocation and all-cause, complications and mortality at 1, 2 and 5 years. If dual mobility THA is found to be superior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 1536 patients from at least 48 hospitals over 3 years.Ethics and dissemination Ethics approval has been granted (Sydney Local Health District - Royal Prince Alfred Hospital Zone (approval X20-0162 and 2020/ETH00680) and site-specific approvals). Participant recruitment is via an opt-out consent process as both treatments are considered accepted, standard practice. The trial is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.Trial registration number ACTRN12621000069853. more...
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- 2022
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38. A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma
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Bartlett, Nancy L., Herrera, Alex F., Domingo-Domenech, Eva, Mehta, Amitkumar, Forero-Torres, Andres, Garcia-Sanz, Ramon, Armand, Philippe, Devata, Sumana, Izquierdo, Antonia Rodriguez, Lossos, Izidore S., Reeder, Craig, Sher, Taimur, Chen, Robert, Schwarz, Sylvia E., Alland, Leila, Strassz, Andras, Prier, Kim, Choe-Juliak, Cassandra, and Ansell, Stephen M. more...
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- 2020
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39. Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data
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Barr, David A, Lewis, Joseph M, Feasey, Nicholas, Schutz, Charlotte, Kerkhoff, Andrew D, Jacob, Shevin T, Andrews, Ben, Kelly, Paul, Lakhi, Shabir, Muchemwa, Levy, Bacha, Helio A, Hadad, David J, Bedell, Richard, van Lettow, Monique, Zachariah, Rony, Crump, John A, Alland, David, Corbett, Elizabeth L, Gopinath, Krishnamoorthy, Singh, Sarman, Griesel, Rulan, Maartens, Gary, Mendelson, Marc, Ward, Amy M, Parry, Christopher M, Talbot, Elizabeth A, Munseri, Patricia, Dorman, Susan E, Martinson, Neil, Shah, Maunank, Cain, Kevin, Heilig, Charles M, Varma, Jay K, von Gottberg, Anne, Sacks, Leonard, Wilson, Douglas, Squire, S Bertel, Lalloo, David G, Davies, Gerry, and Meintjes, Graeme more...
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- 2020
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40. Cross-validation of existing signatures and derivation of a novel 29-gene transcriptomic signature predictive of progression to TB in a Brazilian cohort of household contacts of pulmonary TB
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Leong, Samantha, Zhao, Yue, Ribeiro-Rodrigues, Rodrigo, Jones-López, Edward C., Acuña-Villaorduña, Carlos, Rodrigues, Patricia Marques, Palaci, Moises, Alland, David, Dietze, Reynaldo, Ellner, Jerrold J., Johnson, W. Evan, and Salgame, Padmini more...
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- 2020
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41. Hand-Held Echocardiography by Advanced Practice Providers in Patients with Congestive Heart Failure
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Tagle-Cornell, Maria Cecilia, primary, Novais, Barbara S., additional, Wen, Songnan, additional, Shipman, Justin N., additional, Mandale, Deepa R., additional, Flom, Andrew P., additional, Sahnan, Sandeep K., additional, Kriz, Lindsey M., additional, Alland, Michelle L., additional, Bird, Christen W., additional, and Naqvi, Tasneem Z., additional more...
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- 2024
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42. Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure
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Savic, Radojka, Nahid, Payam, Jayakumar, A, Savic, RM, Everett, CK, Benator, D, Alland, D, Heilig, CM, Weiner, M, Friedrich, SO, Martinson, NA, and Kerrigan, A
- Published
- 2016
43. Memória de trabalho e capacidade física em idosos
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Lima, Flávio Anselmo Silva de, primary, Barros, Jônatas de França, additional, Silva, Erick Job Santos Pereira da, additional, Silva, Alana Monteiro Bispo da, additional, Rocha, Arthur Alland Cruz Morais, additional, Fernandes, Ingrid Luana Toscano, additional, Almeida, Hélio Franklin Rodrigues de, additional, Barros, Luiz Felipe Ferreira, additional, Silva, André Ribeiro da, additional, and Neto, Leônidas de Oliveira, additional more...
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- 2021
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44. Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings
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Luetkemeyer, Anne F, Firnhaber, Cynthia, Kendall, Michelle A, Wu, Xingye, Mazurek, Gerald H, Benator, Debra A, Arduino, Roberto, Fernandez, Michel, Guy, Elizabeth, Johnson, Pamela, Metchock, Beverly, Sattler, Fred, Telzak, Edward, Wang, Yun F, Weiner, Marc, Swindells, Susan, Sanne, Ian M, Havlir, Diane V, Grinsztejn, Beatriz, and Alland, David more...
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Rare Diseases ,Prevention ,Biodefense ,HIV/AIDS ,Clinical Research ,Vaccine Related ,Infectious Diseases ,Tuberculosis ,Emerging Infectious Diseases ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Infection ,Good Health and Well Being ,Adult ,Antibiotics ,Antitubercular ,Brazil ,DNA ,Bacterial ,Drug Resistance ,Bacterial ,Female ,Humans ,Male ,Middle Aged ,Mutation ,Mycobacterium tuberculosis ,Nucleic Acid Amplification Techniques ,Prevalence ,Rifampin ,Sensitivity and Specificity ,South Africa ,Sputum ,Tuberculosis ,Pulmonary ,United States ,Xpert MTB/RIF ,tuberculosis diagnosis ,respiratory isolation ,nontuberculous mycobacteria ,HIV/tuberculosis coinfection ,AIDS Clinical Trials Group A5295 and Tuberculosis Trials Consortium Study 34 Teams ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundThe Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.MethodsXpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa.ResultsOf 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%.ConclusionsIn the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation. more...
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- 2016
45. Phase variation in Mycobacterium tuberculosis glpK produces transiently heritable drug tolerance
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Safi, Hassan, Gopal, Pooja, Lingaraju, Subramanya, Ma, Shuyi, Levine, Carly, Dartois, Veronique, Yee, Michelle, Li, Liping, Blanc, Landry, Liang, Hsin-Pin Ho, Husain, Seema, Hoque, Mainul, Soteropoulos, Patricia, Rustad, Tige, Sherman, David R., Dick, Thomas, and Alland, David more...
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- 2019
46. Mycobacterium tuberculosis progresses through two phases of latent infection in humans
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Roberto Colangeli, Aditi Gupta, Solange Alves Vinhas, Uma Deepthi Chippada Venkata, Soyeon Kim, Courtney Grady, Edward C. Jones-López, Patricia Soteropoulos, Moisés Palaci, Patrícia Marques-Rodrigues, Padmini Salgame, Jerrold J. Ellner, Reynaldo Dietze, and David Alland more...
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Science - Abstract
Here, Colangeli et al. use a human household contact cohort to measure the rate of mutation and evolution of Mycobacterium tuberculosis strains and find that long term latency is characterized by reduced mutation rates compared to latency in the first year, coinciding with clinical risk of developing active TB. more...
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- 2020
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47. Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response
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Stephanus T. Malherbe, Ray Y. Chen, Patrick Dupont, Ilse Kant, Magdalena Kriel, André G. Loxton, Bronwyn Smith, Caroline G. G. Beltran, Susan van Zyl, Shirely McAnda, Charmaine Abrahams, Elizna Maasdorp, Alex Doruyter, Laura E. Via, Clifton E. Barry, David Alland, Stephanie Griffith- Richards, Annare Ellman, Thomas Peppard, John Belisle, Gerard Tromp, Katharina Ronacher, James M. Warwick, Jill Winter, and Gerhard Walzl more...
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Tuberculosis ,18F-FDG ,PET-CT ,Tuberculosis treatment response ,Mycobacterium tuberculosis ,Quantitative imaging analysis ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. Results Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. Conclusions Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities. more...
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- 2020
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48. Reversible gene silencing through frameshift indels and frameshift scars provide adaptive plasticity for Mycobacterium tuberculosis
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Gupta, Aditi and Alland, David
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- 2021
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49. Author Correction: A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome
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Poonam Chitale, Alexander D. Lemenze, Emily C. Fogarty, Avi Shah, Courtney Grady, Aubrey R. Odom-Mabey, W. Evan Johnson, Jason H. Yang, A. Murat Eren, Roland Brosch, Pradeep Kumar, and David Alland
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Science - Published
- 2022
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50. Lack of association of novel mutation Asp397Gly in aftB gene with ethambutol resistance in clinical isolates of Mycobacterium tuberculosis
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Giri, Astha, Safi, Hassan, Cabibbe, Andrea Maurizio, Gupta, Shraddha, Narang, Anshika, Tyagi, Gaurav, Shrivastava, Kamal, Kumar, Chanchal, Kumar Sharma, Naresh, Lingaraju, Subramanya, Trovato, Alberto, Battaglia, Simone, Cirillo, Daniela Maria, Bose, Mridula, Alland, David, and Varma-Basil, Mandira more...
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- 2019
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