Author: "Lawrence SO" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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1. Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model

Author: Claire M. Naftalin, Rupangi Verma, Meera Gurumurthy, Kim Hor Hee, Qingshu Lu, Benjamin Chaik Meng Yeo, Kin Hup Tan, Wenwei Lin, Buduo Yu, Kok Yong Seng, Lawrence Soon-U Lee, and Nicholas I. Paton
Subjects: Medicine, Science
Abstract: Abstract COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA −0.10 ± 0.13ΔlogCFU versus −0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference −0.01, 95% CI −0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.
Published: 2018
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2. Strongyloides Hyperinfection Associated with Enterococcus faecalis Bacteremia, Meningitis, Ventriculitis and Gas-Forming Spondylodiscitis: A Case Report

Author: Liang En Wee, Su Wai Khin Hnin, Zheyu Xu, and Lawrence Soon-U Lee
Subjects: strongyloides, hyperinfection, enterococcus, emphysematous spondylodiscitis, Medicine
Abstract: An elderly Singaporean male with no travel history was hospitalized for fever and altered mental status. Blood cultures grew Enterococcus faecalis, and given a preceding history of steroid use and peripheral eosinophilia, Strongyloides hyperinfection was suspected. Stool specimens were positive for Strongyloides stercoralis larvae over four days, and larvae were also isolated in an early morning nasogastric aspirate specimen prior to initiation of ivermectin. A cerebrospinal fluid examination was consistent with partially treated bacterial meningitis and ventriculitis was demonstrated on neuroimaging. In view of a persistent fever, a further imaging evaluation was performed, which demonstrated bilateral pneumonia as well as the unusual finding of gas-forming emphysematous spondylodiscitis and left psoas abscesses. Despite the early suspicion of Strongyloides hyperinfection, commencement of appropriate antibiotics and anti-helminthics, microbiological clearance of bacteremia as well as clearance of S. stercoralis from the stool, the patient still succumbed to infection and passed away 11 days after admission.
Published: 2020
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3. Manipulation of Cognitive Load Variables and Impact on Auscultation Test Performance

Author: Chen, Ruth, Grierson, Lawrence, and Norman, Geoffrey
Abstract: Health profession educators have identified auscultation skill as a learning need for health professional students. This article explores the application of cognitive load theory (CLT) to designing cardiac and respiratory auscultation skill instruction for senior-level undergraduate nursing students. Three experiments assessed student auscultation performance following instructional manipulations of the three primary components of cognitive load: intrinsic, extraneous, and germane load. Study 1 evaluated the impact of intrinsic cognitive load by varying the number of diagnoses learned in one instruction session; Study 2 evaluated the impact of extraneous cognitive load by providing students with single or multiple examples of diagnoses during instruction; and Study 3 evaluated the impact of germane cognitive load by employing mixed or blocked sequences of diagnostic examples to students. Each of the three studies presents results that support CLT as explaining the influence of different types of cognitive processing on auscultation skill acquisition. We conclude with a discussion regarding CLT's usefulness as a framework for education and education research in the health professions.
Published: 2015
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4. Preservice Teachers' Perceptions of Neuroscience, Medicine, and Students with ADHD

Author: Zambo, Debby, Zambo, Ron, and Sidlik, Lawrence
Abstract: Neuroscience is revealing how the brains of individuals with Attention Deficit Hyperactivity Disorder (ADHD) function, and advances in medicine are leading to treatments. This study investigated preservice teachers' knowledge and beliefs about students with ADHD. The majority of preservice teachers knew someone with ADHD, which, along with courses taken and the media, allowed them to understand ADHD's signs, symptoms, and challenges. However, in general their responses showed a lack of understanding. The authors conclude that preservice teachers need information embedded in their coursework and mentors who understand know how to work with students with ADHD.
Published: 2013

5. Tracking Telehealth Needs for Individuals With Sickle Cell Disease Through the COVID‐19 Pandemic: A Cross‐Sectional Survey Study

Author: Marsha Treadwell, Lisa Du, Yemi Lawrence, Maxine Gaspar, Kathryn Hassell, Sanjay Shah, Moses Akpan, Nicole Crook, Marcia Taylor, Srila Gopal, and For the Pacific Sickle Cell Regional Collaborative
Subjects: access to care, quality of care, sickle cell disease, telehealth, Medicine
Abstract: ABSTRACT Background and Aim Pervasive disparities characterize sickle cell disease (SCD) care, including limited access to SCD specialists. Rapid deployment of remote healthcare provision and support during the COVID‐19 pandemic provides an opportunity to understand telehealth barriers/facilitators for SCD. We aimed to evaluate telehealth experiences and satisfaction for routine visits among adults and caregivers of children with SCD within a US regional collaborative. Methods 151 adults ≥ 18 [median (IQR) = 36 (28, 43) years], and 94 caregivers [median child age (IQR) = 12 (7, 14) years] completed a 30‐item online survey in 2021 assessing systems issues such as reliable Internet; health information sharing; and consumer focus (e.g., visit started on time). A multivariable logistic regression model was used to evaluate relations between independent variables and the outcome overall satisfaction with telehealth. Results Patients were primarily diagnosed with sickle cell anemia (60.8%) and prescribed hydroxyurea (57.6%). Satisfaction with telehealth was high (> 90%), but 60.6% of caregivers gave the highest rating compared with 44.9% of adults (p = 0.02). Few accessibility/technical issues were cited, however, caregivers reported more often having home support for telehealth (80.9% vs. 63.6%, p = 0.003). In multivariable analyses, participants seen in large centers (> 200) were more likely to give the highest satisfaction ratings compared with those in smaller centers (
Published: 2024
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6. The Types and Effectiveness of Mobile Health Applications Used in Improving Oral Cancer Knowledge: A Mixed Methods Systematic Review

Author: Kehinde Kazeem Kanmodi, Afeez Abolarinwa Salami, Kamini Shah, Fatemeh Vida Zohoori, and Lawrence Achilles Nnyanzi
Subjects: app, knowledge, mobile health, oral cancer, systematic review, Medicine
Abstract: ABSTRACT Background and Aims The global burden of oral cancer (OC) is enormous. Mobile health applications have been found to play a promising role in cancer prevention; however, no known systematic review evidence exists on whether the use of mobile health applications is effective in increasing public knowledge of OC or not. Therefore, this systematic review aimed to synthesize evidence on the types and effectiveness of mobile health applications used for improving OC knowledge. Methods This study adopted a mixed methods systematic review design. The review methodology was informed by Joanna Brigg's Institute's PRISMA checklist and the AMSTAR‐2 guidelines. The literature used for this review were obtained through the search of multiple sources, including 12 electronic databases, web sources, and manual searching of the reference lists and citations of the included articles. Quality appraisal of the included articles was done using the Mixed Methods Appraisal Tool, after which relevant data were collected, synthesized, and configured. Results A total of three high‐quality articles, from two studies conducted in India, were included in this review. The studies investigated 574 participants, who are predominantly doctors and community members, on two Android‐based mobile health applications (M‐OncoED and Prayaas). Only Prayaas was found to significantly increase OC knowledge among its users (p
Published: 2024
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7. Work-related impacts on doctors’ mental health: a qualitative study exploring organisational and systems-level risk factors

Author: Paul R Ward, Sharon Lawn, Alison Weightman, Belinda Lunnay, Kristen Foley, Michael Baigent, Diana Lawrence, Virginia Drummond, and Mandi Baker
Subjects: Medicine
Abstract: Background Protecting doctors’ mental health has typically focused on individuals, rather than addressing organisational and structural-level factors in the work environment.Objectives This study uses the socioecological model (SEM) to illuminate and explore how these broader factors inform the mental health of individual doctors.Design Semi-structured interviews (20–25 hours) and ethnographic observations (90 hours) involving work shadowing doctors (n=14).Participants Doctors representing various career stages, specialty areas, genders and cultural backgrounds.Setting Three specialties in a public South Australian hospital. Thematic analysis revealed work-related risk factors for poor mental health.Results The SEM framework was used to analyse the work environment’s impact on doctors’ mental health. The analysis identified how the layers interconnect to influence risk factors for individual doctors. Microsystem: lack of control over career advancement, disenfranchisement due to understaffing and concerns about handling complex cases relative to experience. Mesosystem: negative impacts of shift work and fragmented teams, leading doctors to absorb pressure despite exhaustion to maintain professional credibility. Exosystem: high patient loads with time constraints and geographical limitations hindering care delivery, compounded by administrative burdens. Macrosystem: the commercialisation of medicine emphasising corporatisation and bureaucratic processes, which devalues professional autonomy.Conclusions This study highlights how doctors experience layers of interconnected factors that compromise their mental health but over which they have very little control. Interventions must therefore address these issues at organisational and systemic levels, for which starting points evident within our data are identified.
Published: 2024
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8. Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.

Author: Lawrence Soon-U Lee, Kok-Yong Seng, Ling-Zhi Wang, Wei-Peng Yong, Kim-Hor Hee, Thomas I Soh, Andrea Wong, Pei F Cheong, Richie Soong, Nur S Sapari, Ross Soo, Lu Fan, Soo-Chin Lee, and Boon C Goh
Subjects: Medicine, Science
Abstract: BACKGROUND:Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods. METHODS:Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5. RESULTS:SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p
Published: 2016
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9. Definitions of Insanity in College Students

Author: Geiger, John F. and Weinstein, Lawrence
Abstract: The legal concept of insanity has had many definitions throughout the years, and the precise definition used is critical in determining the status of a person in the legal system. Past research has demonstrated that different professions working in the legal system cannot agree on the definition of insanity (Weinstein & Geiger, 2003). However, many times the final decision of sanity vs. insanity is made by 12 laypersons-the jury. In the present study, 177 undergraduate students were asked to rate seven different definitions of insanity. There were differences in the level of agreement between the seven definitions, and also differences between professionals and college students were found for 3 definitions: The medical model, the sociological model, and the psychometric model. In addition, depression and alcoholism were viewed as more onset controllable than paranoid schizophrenia. (Contains 3 tables.)
Published: 2008

10. Anatomists Debate the Value of a Teaching Credential

Author: Rizzolo, Lawrence J. and Drake, Richard L.
Abstract: Fewer and fewer programs are training graduate students and postdoctoral fellows in the classical anatomical disciplines. Nonetheless, there remains a need at all levels of clinical and basic science education for skilled instructors of anatomy, histology, and embryology. Two sessions at the 2006 annual meeting of the American Association of Anatomists (AAA) explored whether a system of accreditation would benefit students, institutions, and training programs. Although the value of accreditation was controversial, three challenges for the various anatomical societies emerged from these discussions: (1) To identify the skills and knowledge that should be shared among all anatomists, and the more specific skills and knowledge needed for the diverse settings in which anatomists work. (2) To address the historical inattention of institutions to the training of educators. (3) To develop strategies to lobby institutions and national organizations to support the training and work of educators in the anatomical sciences. One approach to meeting these challenges would be to develop guidelines for training programs. These guidelines would help graduate students seek the training they need, provide institutions with a benchmark to assess or develop training programs, and provide the basis for focusing lobbying efforts targeted at institutions or existing accreditation bodies. (Contains 3 tables.)
Published: 2008
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11. Newcastle Disease Virus Expressing Cap Gene of Porcine Circovirus Type 2 Confers Protection in Mice and Induced Long-Lasting Neutralizing Antibodies in Pigs

Author: Sohini Dey, Rudhreswaran Murugasamy, Lukumoni Buragohain, Ajai Lawrence D’silva, Jayashree Sarma, Arpita Bharali, Saravanan Ramakrishnan, Mani Saminathan, Nagendra Nath Barman, Vikram N. Vakharia, and Madhan Mohan Chellappa
Subjects: Porcine Circovirus 2, Newcastle disease virus, recombinant vector, immune response, mice and pig models, Medicine
Abstract: Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated the efficacy of two novel recombinant Newcastle disease virus (NDV) strain R2B vectored vaccines that express the cap gene of PCV2 alone and along with the transmembrane and cytoplasmic tail (TMCT) domains of the NDV F gene. The efficacy of the vaccine candidates was studied in mouse and pig models. Methods: Six-week-old BALB/c mice were divided into five groups and immunized intramuscularly three times at 14-day intervals with various vaccine candidates, namely rNDV-R2B-PCVcap-TMCT, rNDV-R2B-PCVcap, and CircoFLEX commercial vaccine, along with controls. Following immunization and PCV2d virus challenge, multiple assays assessed the immune responses in animal trials. In the pig animal trial, pigs were divided into four groups: a control group (PBS), NDV-vectored PCVcap-TMCT group, NDV-vectored-PCVcap group, and CircoFLEX vaccine group. Pigs were immunized intramuscularly twice at 28-day intervals. Blood samples were collected at regular intervals over 70 days to evaluate the humoral and cell-mediated immune responses. Results: Both mice and pigs’ trials indicated that the NDV-vectored PCV2 cap-TMCT vaccine candidate elicited superior immune responses. In mice, the rNDV-R2B-PCVcap-TMCT group showed enhanced humoral and cellular immunity, increased PCV2-specific antibody levels, higher CD4+/CD8+ ratio, elevated IFN-γ and TNF-α levels, decreased IL-10 levels, reduced viral loads, and minimal histopathological changes. In pigs, the NDV-vectored PCVcap-TMCT group demonstrated better antibody responses, cytokine profiles (IFN-γ and IL-10), and higher levels of PCV2-specific neutralizing antibodies against the PCV2a, PCV2b and PCV2d genotypes when compared to other groups. Conclusions: These findings suggest NDV-vectored PCVcap-TMCT vaccine candidate, expressing the cap gene of PCV2 along with the TMCT domain, offers a promising alternative for protecting against PCV2 infection, potentially addressing the challenges posed by emerging PCV2 strains in the swine industry.
Published: 2024
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12. A Nation-wide mapping programme for genetic syndromes associated with cancer

Author: Cristina Lopez Escola, David Ballesteros, Christina Macano, Naim Qandil, Lawrence Stagnetto, Lauren Olivero, Lindsay Rainford, Paul Pereira, Pamela Estella, Christine Gill, and Terri McVeigh
Subjects: Medicine
Abstract: Introduction: Gibraltar Health Authority in collaboration with Dr Terri McVeigh (Geneticist at Royal Marsden NHS Foundation Trust) have implemented a cutting-edge programme to screen for patients with certain cancer types who meet criteria for Specialist-led germline testing since January 2023. This initiative aligns with NICE guidance (DG27 and DG42), NHS Long Term Plan and NHS England National Genomic Test Directory.A - Lynch Syndrome (LS) is a hereditary condition associated with increased risk of several cancer types, including colorectal, gastrointestinal and biliary tract, genitourinary system and pancreatic cancer. It is caused by a germline pathogenic variant in one of four DNA MisMatch Repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2.Approximately one in 250 individuals have Lynch Syndrome; half of whom are estimated to develop colorectal cancer.B - BRCA1 and BRCA2 are 2 important tumour-suppressor genes against breast, ovarian, prostate, pancreatic and other cancers. BRCA1 gene mutations can increase a woman's risk of developing breast cancer by the age of 70 to 65–85% and ovarian cancer to 30–50%. However, BRCA2 gene mutations can increase a woman's risk of developing breast cancer by the age of 70 to 40–85% and ovarian cancer to 10–20%. This compares to the 12.5% lifetime risk of breast cancer and 2% risk of ovarian cancer for the average British woman.Approximately one in 400 individuals are estimated to carry a BRCA1/BRCA2 mutation. Materials and methods: Tissue-based samples from biopsy or surgery are identified at weekly Oncology Multi-Disciplinary Team (MDT) meeting; based on the criteria outlined by NHS England National Genomic Test Directory.These samples are air-shipped to Royal Marsden for testing; with target Turn Around Time (TAT) of 14 days from the date of sample arrival to Clinical Genomics laboratory.Strong family history of cancer, alterations on MMR or BRCA1-2 routinely prompt referral to Dr McVeigh for consideration of germline testing. Results and discussion: At 13-month landmark, a total of 94 non-breast probands have been screened as eligible for initial testing at MDT; 89 of whom have proceeded to testing. One case was taken off programme for overseas location of tissue blocks; remaining four are planned for surgery, which will provide with further material.Excluding breast cases on this first interim analysis, 11 referrals have been sent to Dr McVeigh for germline testing: four MSI-high colon cancers; four Micro-Satellite Stable (MSS) colon cancer patients aged 40 or with family history; a co-mutation in ATM/CDK12 in prostate and two BRCA2 mutations in prostate and pancreatic cancer probands. Conclusion: From 93 non-breast probands, four colon cancers are pending conclusion on LS and two are awaiting outcome on BRCA2 mutation (prostate and pancreatic) over 30,000 Gibraltarian population; which falls well below general estimates.Counselling on individual cancer risk over life time, risk-reducing surgery, chemo-prevention, tailored screening and surveillance programmes are the main aimed benefits.Hand-in-hand liaison with Royal Marsden and Clinical Nurse Specialists have been key to implement and conduct this programme successfully.Stepped processes are being audited for Quality Improvement, care excellence, patients and caregivers' satisfaction.
Published: 2024
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13. Evaluation of reliability generalization of Conner-Davison Resilience Scale (CD-RISC-10 and CD-RISC-25): A Meta-analysis.

Author: Ajele Kenni Wojujutari, Erhabor Sunday Idemudia, and Lawrence Ejike Ugwu
Subjects: Medicine, Science
Abstract: BackgroundResilience, a critical multi-faceted construct in psychological research, is often measured using Conner-Davison Resilience Scale (CD-RISC-10 and CD-RISC-25). This reliability generalization (RG) meta-analysis delves into evaluate the level of reliability generalization estimate of both CD-RISC-10 and CD-RISC-25 in assessing resilience across diverse populations and settings.MethodsA reliability generalization meta-analysis on the psychometric properties of CD-RISC-10 and CD-RISC-25 was conducted, encompassing 27 studies. The original versions' psychometric properties were systematically retrieved from databases including PubMed, PsycINFO, Google Scholar, Web of Science, Science Direct, and Scopus, with a focus on studies published between 2018 and 2023. The study protocol, including the specific methods for the reliability generalization meta-analysis, was pre-registered in the Prospero database (registration number CRD42023479052). This pre-registration ensures transparency and minimizes the risk of bias in the study design and analysis.ResultsThe analysis revealed a combined estimated overall estimate of Cronbach's Alpha of 0.89 (95% CI [0.87, 0.91], z = 77.20, p < 0.05), indicating a high level of reliability for CD-RISC-10 and CD-RISC-25. CD-RISC-10 exhibited an overall estimate of Cronbach's Alpha of 0.8732 (95% CI [0.85, 0.10], z = 69.81, p < 0.05), indicating a high level of reliability, while CD-RISC-25 also demonstrated an overall estimate of Cronbach's Alpha of 0.8922 (95% CI [0.87, 0.91], z = 77.20, p < 0.001), indicating a high level of reliability. Furthermore, CD-RISC-10 displayed commendable reliability (ωα+ = 0.86), slightly lower compared to the impressive reliability of CD-RISC-25 (ωα+ = 0.89), with a significant difference (t = 0.1159, p > 0.001). The mixed-effects model revealed a non-significant moderating effect of the CD-RISC language version on reliability estimates (coefficient = -0.0017, p ConclusionThe results affirm the high overall reliability of both CD-RISC-10 and CD-RISC-25, with CD-RISC-25 exhibiting a slightly superior level. The non-significant moderating effect of language version suggests that the psychometric properties of these scales remain robust across different linguistic adaptations. These findings enhance our understanding of the CD-RISC scales, providing practitioners, researchers, and clinicians valuable insights for informed scale selection in diverse contexts. The commendable reliability of both scales underscores their utility in assessing and promoting resilience across varied populations and settings. Future research should explore specific contexts, demographics, and applications, enhancing their utility for diverse populations and settings.
Published: 2024
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14. Improving cardiorespiratory fitness and quality of life among heart failure patients: A comparative study of circuit resistance training and myofascial release techniques.

Author: Sergio R Thomaz, Cássia Da Luz Goulart, Natália Turri-Silva, Felipe A Teixeira, Luis Freitas, Glauco Lima Rodrigues, Graziella França B Cipriano, Gerson Cipriano, and Lawrence P Cahalin
Subjects: Medicine, Science
Abstract: BackgroundHeart failure (HF) imposes limitations due to severe dyspnea and fatigue, which are often linked to diminished exercise tolerance, potentially influenced by compromised microvascular density, blood flow, and muscle strength. Myofascial release techniques (MRT) have demonstrated the capacity to enhance blood flow by reducing fascial tension.PurposeTo assess the impact of incorporating MRT into Circuit Resistance Training (CRT) in comparison to an unsupervised home-based rehabilitation (RUHB) program on exercise tolerance (ET), muscle strength (MS), quality of life (QoL), and depression in patients with HF.MethodsA randomized clinical trial involved HF patients with reduced ejection fraction (HFrEF, ejection fraction ResultsThirty-eight patients (14 in CRT, 14 in CRT+MRT, and 10 in RUHB), with a mean age of 55 years and 50% male, completed the study. After 12 weeks, only the CRT group displayed a significant effect in certain ET variables VO2 peak [baseline 12 (9-15) vs post 16 (11-19) ml/kg/min, pConclusionOur findings suggest that CRT alone is sufficient to enhance cardiorespiratory function and muscle capacity, improve the quality of life, and alleviate depression in individuals with HF.
Published: 2024
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15. Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model.

Author: Nabarun Chakraborty, George Dimitrov, Swapna Kanan, Alexander Lawrence, Candance Moyler, Aarti Gautam, Oluseyi O Fatanmi, Stephen Y Wise, Alana D Carpenter, Rasha Hammamieh, and Vijay K Singh
Subjects: Medicine, Science
Abstract: Multiple accidents in nuclear power plants and the growing concerns about the misuse of radiation exposure in warfare have called for the rapid determination of absorbed radiation doses (RDs). The latest findings about circulating microRNA (miRNAs) using several animal models revealed considerable promises, although translating this knowledge to clinics remains a major challenge. To address this issue, we randomly divided 36 nonhuman primates (NHPs) into six groups and exposed these groups to six different radiation doses ranging from 6.0-8.5 Gy in increments of 0.5 Gy. Serum samples were collected pre-irradiation as well as three post-irradiation timepoints, namely 1, 2 and 6 days post-total body irradiation (TBI). Generated from a deep sequencing platform, the miRNA reads were multi-variate analyzed to find the differentially expressed putative biomarkers that were linked to RDs, time since irradiation (TSI) and sex. To increase these biomarkers' translational potential, we aligned the NHP-miRNAs' sequences and their functional responses to humans following an in-silico routine. Those miRNAs, which were sequentially and functionally conserved between NHPs and humans, were down selected for further analysis. A linear regression model identified miRNA markers that were consistently regulated with increasing RD but independent TSI. Likewise, a set of potential TSI-markers were identified that consistently shifted with increasing TSI, but independent of RD. Additional molecular analysis found a considerable gender bias in the low-ranges of doses when the risk to radiation-induced fatality was low. Bionetworks linked to cell quantity and cell invasion were significantly altered between the survivors and decedents. Using these biomarkers, an assay could be developed to retrospectively determine the RD and TSI with high translational potential. Ultimately, this knowledge can lead to precise and personalized medicine.
Published: 2024
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16. Enhancing childhood immunization coverage in Mozambique and Malawi: Study protocol of a mixed methods evaluation of the ‘Let’s talk about vaccines’ multisite community-based participatory project

Author: Linda Shuro, Emily Lawrence, Lucia Knight, Helen Schneider, and Hanani Tabana
Subjects: Medicine, Science
Published: 2024

17. Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.

Author: Cham, Jason, Zhang, Li, Kwek, Serena, Paciorek, Alan, He, Tao, Fong, Grant, Oh, David Y, and Fong, Lawrence
Subjects: CD8-Positive T-Lymphocytes, Humans, Melanoma, Skin Neoplasms, Granulocyte-Macrophage Colony-Stimulating Factor, Receptors, Antigen, T-Cell, Recombinant Proteins, Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Adult, Middle Aged, Male, High-Throughput Nucleotide Sequencing, CTLA-4 Antigen, Prostatic Neoplasms, Castration-Resistant, Ipilimumab, immunology, medicine, oncology
Abstract: BackgroundCTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.MethodsWe used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.ResultsWhile melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p
Published: 2020

18. Obesity-linked suppression of membrane-bound O-acyltransferase 7 (MBOAT7) drives non-alcoholic fatty liver disease.

Author: Helsley, Robert, Varadharajan, Venkateshwari, Brown, Amanda, Gromovsky, Anthony, Schugar, Rebecca, Ramachandiran, Iyappan, Fung, Kevin, Kabbany, Mohammad, Banerjee, Rakhee, Neumann, Chase, Finney, Chelsea, Pathak, Preeti, Orabi, Danny, Osborn, Lucas, Massey, William, Zhang, Renliang, Kadam, Anagha, Sansbury, Brian, Pan, Calvin, Sacks, Jessica, Lee, Richard, Crooke, Rosanne, Graham, Mark, Lemieux, Madeleine, Gogonea, Valentin, Kirwan, John, Allende, Daniela, Civelek, Mete, Fox, Paul, Rudel, Lawrence, Lusis, Aldons, Spite, Matthew, and Brown, J
Subjects: NAFLD, hepatology, human biology, medicine, mouse, triacylglycerol, Acylation, Acyltransferases, Animals, Disease Progression, Humans, Membrane Proteins, Mice, Non-alcoholic Fatty Liver Disease, Obesity
Abstract: Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound O-acyltransferase domain-containing 7 (MBOAT7) and transmembrane channel-like 4 (TMC4) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017). Based on hepatic expression quantitative trait loci analysis, it has been suggested that MBOAT7 loss of function promotes liver disease progression (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017), but this has never been formally tested. Here we show that Mboat7 loss, but not Tmc4, in mice is sufficient to promote the progression of NAFLD in the setting of high fat diet. Mboat7 loss of function is associated with accumulation of its substrate lysophosphatidylinositol (LPI) lipids, and direct administration of LPI promotes hepatic inflammatory and fibrotic transcriptional changes in an Mboat7-dependent manner. These studies reveal a novel role for MBOAT7-driven acylation of LPI lipids in suppressing the progression of NAFLD.
Published: 2019

19. Expository Writing in Chinese. International Studies, East Asian Language Texts, No. 5.

Author: Kansas Univ., Lawrence. Center for East Asian Studies. and McMahon, Keith
Abstract: This text is intended for use by advanced students of the Chinese language to learn to write at the college level in modern Chinese. The first ten lessons teach how to progress from the spoken structures to their contemporary written forms. Each lesson contains a text with a familiar form, notes on grammatical structures, and exercises. The text and exercises are largely in Chinese; notes are in English and Chinese. Text forms include a letter to a friend, an anecdote, a short travel essay, formal letters, an expository essay on Chinese mythology, a discussion of Chinese medicine, an essay in appreciation of a Chinese poem, and an essay on Chinese landscape painting. An index follows these lessons. Lessons 11 through 14 contain brief texts of contemporary Chinese writers, selected for variation in style, and exercises. A second index follows this section. Indexes include ideograph, Romanized form, and lesson and note references. (MSE)
Published: 1987

20. Research Training in Medical Informatics: The Stanford Experience.

Author: Shortliffe, Edward H. and Fagan, Lawrence M.
Abstract: Stanford University created an interdisciplinary program to train researchers and academic leaders in the field of medical information sciences. The program is described, identifying experiences of interest to people developing such a program. The program's background and history, students, curriculum and philosophy, and lessons learned are discussed. (Author/MSE)
Published: 1989

21. Effect of Physician Tutorials on Prescribing Patterns of Graduate Physicians.

Author: Klein, Lawrence E.
Abstract: Physicians in an experimental group were surveyed to assess their knowledge of the effectiveness, cost, and side effects of antibiotics, and a tutorial was developed to modify some prescribing patterns. Prescribing patterns were statistically different. (Author/MLW)
Published: 1981

22. Patient-reported outcome differences for navigated and robot-assisted total hip arthroplasty frequently do not achieve clinically important differences: a systematic review.

Author: Lawrence, Kyle W, Rajahraman, Vinaya, Meftah, Morteza, Rozell, Joshua C, Schwarzkopf, Ran, and Arshi, Armin
Subjects: *DECISION support systems, *SURGICAL robots, *RADIOGRAPHY, *TOTAL hip replacement, *MEDICAL technology, *COMPUTER-assisted image analysis (Medicine), *DESCRIPTIVE statistics, *SURGICAL therapeutics, *TREATMENT effectiveness, *SYSTEMATIC reviews, *MEDLINE, *MEDICAL databases, *HEALTH outcome assessment, *QUALITY assurance, *ONLINE information services, *POSTOPERATIVE period, *MEDICINE
Abstract: Introduction: Total hip arthroplasty (THA) using computer-assisted navigation (N-THA) and robot-assisted surgery (RA-THA) has been increasingly adopted to improve implant positioning and offset/leg-length restoration. Whether clinically meaningful differences in patient-reported outcomes (PROMs) compared to conventional THA (C-THA) are achieved with intraoperative technology has not been established. This systematic review aimed to assess whether published relative PROM improvements with technology use in THA achieved minimal clinically important differences (MCIDs). Methods: PubMed/MEDLINE/Cochrane Library were systematically reviewed for studies comparing PROMs for primary N-THA or RA-THA with C-THA as the control group. Relative improvement differences between groups were compared to established MCID values. Reported clinical and radiographic differences were assessed. Review of N-THA and RA-THA literature yielded 6 (n = 2580) and 10 (n = 2786) studies, respectively, for analyses. Results: Statistically significant improvements in postoperative PROM scores were reported in 2/6 (33.3%) studies comparing N-THA with C-THA, though only 1 (16.7%) reported clinically significant relative improvements. Statistically significant improvements in postoperative PROMs were reported in 6/10 (60.0%) studies comparing RA-THA and C-THA, though none reported clinically significant relative improvements. Improved radiographic outcomes for N-THA and RA-THA were reported in 83.3% and 70.0% of studies, respectively. Only 1 study reported a significant improvement in revision rates with RA-THA as compared to C-THA. Conclusions: Reported PROM scores in studies comparing N-THA or RA-THA to C-THA often do not achieve clinically significant relative improvements. Future studies reporting PROMs should be interpreted in the context of validated MCID values to accurately establish the clinical impact of intraoperative technology. [ABSTRACT FROM AUTHOR]
Published: 2024
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23. IRF5 directs colonic inflammation and control of mononuclear phagocyte adaptation to the tissue environment

Author: Corbin, Alastair Lawrence, Powrie, Fiona, and Udalova, Irina
Subjects: 610, Mucosal Immunology, Innate immunity, Immunology, Inflammatory Bowel Disease, Single Cell RNA sequencing, Medicine, Macrophage, IRF5, Lamina Propria, Mononuclear Phagocyte
Abstract: Macrophages are leukocytes of the innate immune system that display great phenotypic plasticity to mediate diverse functions. The ontogeny of tissue resident macrophages has been debated in recent decades. It is now recognised that tissue macrophages can be replenished from embryonically-derived precursors, and/or monocyte intermediates in a tissue specific manner. Interferon Regulatory Factor 5 (IRF5) is a transcription factor that promotes a pro-inflammatory phenotype in macrophages in vitro and in vivo. Indeed, IRF5 contributes to the pathogenesis of experimental inflammatory arthritis, lupus, and obesity via recruitment and activation of effector cells. Research described here as part of this thesis, involves the profiling of the intestinal Mononuclear Phagocyte system to investigate the role of IRF5 in the development of monocyte-derived macrophages in the Colonic Lamina Propria (cLP) which are exclusively replenished by adult Ly6Chi monocytes. Using Mixed Bone Marrow Chimaeras (MBMCs) we showed that in shared environment Wild-Type (WT) cLP macrophages dominated IRF5-deficient (Irf5-/-) cLP macrophages in both steady state and inflammation. The development of in vitro bone marrow derived macrophages, and the reconstitution of the haematopoietic compartment in bone marrow of MBMCs were not significantly affected by IRF5 deficiency. IRF5 promoted the accumulation of WT monocytes in the cLP of MBMCs in a process possibly dependent on the CCL2/CCR2 axis. Furthermore, IRF5 expression committed Ly6Chi monocytes to a pro-inflammatory macrophage fate in the inflamed cLP, characterised by protein expression of the cytokines IL1β, and TNFα, and the expression of Ccl4 and Ccl8 transcripts, whilst loss of IRF5 favoured accumulation of CD11b+ IRF4-dependent Dendritic Cells. Of significance, IRF5 expression might have prevented further differentiation of inflammatory macrophages into tissue-resident macrophages, thus supporting an inflammatory state. Irf5-/- mice were protected from Helicobacter hepaticus + αIL10R colitis. Intriguingly, protection from colitis may also be conferred by the presence of Irf5-/- haematopoietic cells, evidenced by WT:Irf5-/- MBMCs . Modulation of IRF5 activity may therefore be a viable therapeutic strategy. RNA sequencing identified that C1q, Cd81, and Ccl8 were upregulated in WT macrophages from MBMC, which may prove therapeutic targets.
Published: 2017

24. Plagues: How People Responded to Them in the Past Is Studied by Scholars as a Guide in AIDS Crisis.

Author: Biemiller, Lawrence
Abstract: The latest epidemic, acquired immune deficiency syndrome (AIDS), is ending an unprecedented interval of optimism about medicine's ability to conquer illness. (MSE)
Published: 1988

25. Rickettsia prowazekii Attack (Typhus Fever)

Author: Robert Partridge, Devin M. Smith, and Lawrence Proano
Subjects: Rickettsia prowazekii, biology, business.industry, Typhus fever, Medicine, business, biology.organism_classification, Virology
Published: 2024
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26. The prognostic value of advanced MR in gliomas

Author: Kenning, Lawrence, Lowry, Martin, and Pickles, Martin Darren
Subjects: 610, Medicine
Abstract: This work examines the prognostic value of advanced MR at selected time points during the early stages of treatment in glioma patients. In this thesis, serial imaging of glioma patients was conducted using diffusion tensor imaging (DTI), dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) MRI. A methodology for the processing and registration of multiparametric MRI was developed in order to simultaneously sample whole tumour measurements of multiple MR parameters with the same volume of interest. Differences between glioma grades were investigated using functional MR parameters and tested using Kruskal-Wallis tests. A 2-stage logistic regression model was developed to grade lesions from the preoperative MR, with the model retaining the apparent diffusion coefficient, radial diffusivity, anisotropic component of diffusion, vessel permeability and extravascular extracellular space parameters for glioma grading. A multi-echo single voxel spectroscopic sequence was independently investigated for the classification of gliomas into different grades. From preoperative MR, progression-free survival was predicted using the multiparametric MR data. Individual parameters were investigated using Kaplan-Meier survival analysis, before Cox regression modelling was used for a multiparametric analysis. Radial diffusivity, spin–lattice relaxation rate and blood volume fraction calculated from the DTI and DCE MRI were retained in the final model. MR parameter values were also investigated during the early stages of adjuvant treatment. Patients were scanned before and after chemoradiotherapy, with the change in MR parameters as well as the absolute values investigated for their prognostic information. Cox regression analysis was also performed for the adjuvant treatment imaging, with measures of the apparent diffusion coefficient, spin–lattice relaxation rate, vessel permeability and extravascular extracellular space, derived from the DTI and DCE datasets most predictive of progression-free survival. In conclusion, this thesis demonstrates multiparametric MR of gliomas during the early stages of treatment contains useful prognostic information relating to grade and progression-free survival interval.
Published: 2014

27. ACSM Expert Consensus Statement on Exertional Heat Illness: Recognition, Management, and Return to Activity

Author: Susan W. Yeargin, Lawrence E. Armstrong, William O. Roberts, Michael N. Sawka, Yuval Heled, and Francis G. O'Connor
Subjects: Hyperthermia, medicine.medical_specialty, business.industry, Heat exhaustion, Public Health, Environmental and Occupational Health, General Medicine, medicine.disease, Heat illness, Heat generation, Health care, medicine, Etiology, Chain of survival, Orthopedics and Sports Medicine, Intensive care medicine, business, Stroke
Abstract: Exertional heat stroke (EHS) is a true medical emergency with potential for organ injury and death. This consensus statement emphasizes that optimal exertional heat illness management is promoted by a synchronized chain of survival that promotes rapid recognition and management, as well as communication between care teams. Health care providers should be confident in the definitions, etiologies, and nuances of exertional heat exhaustion, exertional heat injury, and EHS. Identifying the athlete with suspected EHS early in the course, stopping activity (body heat generation), and providing rapid total body cooling are essential for survival, and like any critical life-threatening situation (cardiac arrest, brain stroke, sepsis), time is tissue. Recovery from EHS is variable, and outcomes are likely related to the duration of severe hyperthermia. Most exertional heat illnesses can be prevented with the recognition and modification of well-described risk factors ideally addressed through leadership, policy, and on-site health care.
Published: 2023
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28. Implementation and adherence of routine pertussis vaccination (DTP) in a low-resource urban birth cohort

Author: Christian E Gunning, Lawrence Mwananyanda, William B MacLeod, Magdalene Mwale, Donald M Thea, Rachel C Pieciak, Pejman Rohani, and Christopher J Gill
Subjects: Medicine
Abstract: Introduction Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia.Methods Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria–tetanus–pertussis (DTP) vaccinations across the first 14–18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration.Results At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days.Conclusions We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directly-observed, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting.
Published: 2020
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29. Development and Validation of a Syndrome Definition for Suspected Nonfatal Unintentional/Undetermined Intent Stimulant-Involved Overdoses

Author: Cassandra M. Pickens, Herschel Smith, Stephanie Snodgrass, Stephen Liu, and Lawrence Scholl
Subjects: medicine.medical_specialty, Validation study, Psychotropic Drugs, business.industry, medicine.medical_treatment, Public Health, Environmental and Occupational Health, Emergency department, Drug overdose, medicine.disease, Disease control, United States, Stimulant, Undetermined intent, Public health surveillance, Emergency medicine, medicine, Humans, Central Nervous System Stimulants, Centers for Disease Control and Prevention, U.S, Drug Overdose, business, Emergency Service, Hospital, Sentinel Surveillance
Abstract: Objectives To monitor stimulant-involved overdose (SOD) trends, the Centers for Disease Control and Prevention (CDC) developed and evaluated the validity of a syndromic surveillance definition for suspected nonfatal, unintentional/undetermined intent stimulant-involved overdose (UUSOD). Methods We analyzed all emergency department (ED) visits in CDC’s surveillance system that met the UUSOD syndrome definition (January 2018–December 2019). We classified visits as true positive, possible, or not UUSODs after reviewing diagnosis codes and chief complaints. We first assessed whether visits were acute SODs, subsequently classifying acute SODs by intent. The percentage of true-positive UUSODs did not include intentional or possibly intentional visits. We considered all visits with UUSOD diagnosis codes to be acute SODs and reviewed them for intent. We manually reviewed and double-coded a 10% random sample of visits without UUSOD diagnosis codes using decision rules based on signs and symptoms. The overall percentage of true-positive UUSODs was a weighted average of the percentage of true-positive UUSODs based on diagnosis codes and the percentage of true-positive UUSODs determined by manually reviewing visits without codes. Results During 2018-2019, 40 045 ED visits met the syndrome definition for UUSOD. Approximately half (n = 18 793; 46.9%) of 40 045 visits had UUSOD diagnosis codes, indicating acute SOD; of these, 98.6% (n = 18 534) were true-positive UUSODs. Of 2125 manually reviewed visits without UUSOD diagnosis codes, 32.6% (n = 693) were true-positive UUSODs, 54.2% (n = 1151) were possible UUSODs, and 13.2% (n = 281) were not UUSODs. Overall, 63.6% of visits were true-positive UUSODs, 29.3% were possible UUSODs, and 7.1% were not UUSODs. Practice Implications CDC’s UUSOD definition may assist in surveillance efforts with further refinement to capture data on SOD clusters and trends.
Published: 2023

30. Contemporary robotic cardiac surgical training

Author: Arnar Geirsson, Douglas A. Murphy, Serguei Melnitchouk, A. Marc Gillnov, Husam H. Balkhy, Johannes Bonatti, T. Sloane Guy, Lawrence M. Wei, W. Randolph Chitwood, Francis P. Sutter, Eugene A. Grossi, Vinay Badhwar, and Joseph A. Dearani
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Physical therapy, medicine, Surgery, Cardiology and Cardiovascular Medicine, business, Surgical training, Cardiac surgery
Published: 2023
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31. A Batavian in Paris

Author: Principe, Lawrence M., author
Published: 2020
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32. Feasibility of reporting results of large randomised controlled trials to participants: experience from the Fluoxetine Or Control Under Supervision (FOCUS) trial

Author: Martin Dennis, D Cohen, A Thompson, M Smith, A Naqvi, Graham Ellis, A Khan, L Hunt, X Huang, J Andrews, J Foot, J Smith, S Wong, A Stevens, D Bailey, S Johnston, S Jones, R Robinson, A Johnson, S Williams, T Smith, A Ahmed, S Bloom, L Sekaran, D Singh, F Smith, R Greenwood, A Singh, R Brown, J White, S Smith, S Arif, S Ross, S Trippier, S Levy, B Patel, M Khan, A Thomas, S Brown, V Jones, D Wood, S Maguire, U Khan, P Nair, A Smith, G Hann, R Williams, M Cooper, S Jackson, M Hassan, P Kumar, A Metcalf, R Patel, A Wright, S Khan, A Bell, C Williams, M Robinson, K Jones, S Alam, R Shah, J Simpson, K Ali, K Miller, K Kennedy, S Ahmed, J Francis, L Thomas, M Scott, S Nelson, S Clayton, L Zhang, B Charles, P Lopez, A Fleming, C Lambert, A Shah, J Wong, David Burgess, L Wilson, A Siddiqui, S Kumar, A Hassan, D Cooke, M Williams, P Cooper, S Graham, S Morrison, M Holland, C Green, C Edwards, K Subramanian, K Patel, J Mitchell, J Stewart, S Keenan, C Duggan, S McKenna, R Murphy, M Ward, S Walker, S Lewis, R Jones, L Wright, M Edwards, N Sattar, J Mcgee, R Butler, M Wilkinson, S Das, C Kelly, R Cowan, C Brown, K Moore, L Denny, M Harrison, S Patel, R Rodriguez, J Allen, M Kalita, Gillian Mead, A Bowring, A Edwards, J Scott, J Drew, D Ward, L Dixon, K Burton, E Brown, E Epstein, R Miller, F Reid, A Jones, P Murphy, A Ali, N Ahmad, S Noor, C Leonard, A Nair, M Naeem, M Johnson, E Douglas, J Thompson, R Evans, C Jenkins, J Wilson, R Anderson, H Wilson, H Stone, J Ward, L Greenhalgh, P Walker, A Hill, K Stagg, S Naqvi, R Scott, M Hughes, P Jones, M Simpson, K Elliott, M Davy, S Young, Karen Innes, Pippa Tyrrell, A David, Steff Lewis, A Bwalya, C Buckley, S Kelly, C Thomas, I Kane, M Hussain, S Shah, J Roberts, D Morales, C McInnes, N Khan, N Weir, L Hill, J McLaughlin, K Kavanagh, R Clarke, P Thompson, J Price, J Ball, L Benton, E Walton, E Walker, L Burgess, K McCormick, L Wade, C Anderson, S Stevenson, R Blackburn, L Brown, B Clarke, T Khan, S Dhar, L Harrison, S Bell, D Buchanan, A Deary, J Drever, R Fraser, C Graham, K Innes, C McGill, D Perry, A Barugh, G Blair, Y Chun, E Maschauer, J Forbes, M Hackett, G Hankey, A House, E Lundström, Peter Sandercock, Judith Williamson, John Forbes, Graeme Hankey, Maree Hackett, Veronica Murray, Ray French, David Stott, Jonathan Emberson, P Sandercock, M MacLeod, F Sullivan, P Langhorne, H Rodgers, N Hunter, R Parakramawansha, A Fazal, P Taylor, W Rutherford, R Buchan, A MacRaild, R Paulton, S Burgess, D McGowan, J Skwarski, F Proudfoot, J Perry, J Bamford, C Bedford, D Waugh, E Veraque, M Kambafwile, L Makawa, P Smalley, M Randall, L Idrovo, T Thirugnana-Chandran, R Vowden, J Jackson, A Bhalla, C Tam, A Rudd, C Gibbs, J Birns, L Lee Carbon, E Cattermole, A Cape, L hurley, K Marks, S Kullane, N Smyth, E Giallombardo, C Eglinton, D Dellafera, P Reidy, M Pitt, L Sykes, A Frith, V Croome, J Duffy, M Hancevic, L Kerwood, C Narh, C Merritt, J Willson, T Jackson, H Bowler, C Kamara, J Howe, K Stocks, G Dunn, K Endean, F Claydon, S Duty, C Doyle, K Harkness, E Richards, M Meegada, A Maatouk, L Barron, K Dakin, R Lindert, A Majid, P Rana, C Brighouse-Johnson, J Greig, M Kyu, S Prasad, B Mclean, I Alam, Z Ahmed, C Roffe, S Brammer, A Barry, C Beardmore, K Finney, H Maguire, P Hollinshead, J Grocott, I Natarajan, J Chembala, R Sanyal, S Lijko, N Abano, A Remegoso, P Ferdinand, S Stevens, C Stephen, P Whitmore, A Butler, C Causley, R Varquez, G Muddegowda, R Carpio, J Hiden, H Denic, J Sword, F Hall, J Cageao, R Curwen, M James, P Mudd, C Roughan, H Kingwell, A Hemsley, C Lohan, S Davenport, T Chapter, M Hough, D Strain, K Gupwell, A Goff, E Cusack, S Todd, R Partridge, G Jennings, K Thorpe, J Stephenson, K Littlewood, M Barber, F Brodie, S Marshall, D Esson, I Coburn, F Ross, V Withers, E Bowie, H Barcroft, L Miller, P Willcoxson, M Keeling, M Donninson, D Daniel, J Coyle, M Elliott, P Wanklyn, J Wightman, E Iveson, A Porteous, N Dyer, M Haritakis, J Bell, C Emms, P Wood, P Cottrell, L Doughty, L Carr, C Anazodo, M O Neill, J Westmoreland, R Mir, C Donne, E Bamford, P Clark Brown, A Stanners, I Ghouri, A Needle, M Eastwood, M Carpenter, P Datta, R Davey, F Razik, G Bateman, J Archer, V Balasubramanian, L Jackson, R Bowers, J Ellam, K Norton, P Guyler, S Tysoe, P Harman, A Kundu, T Dowling, S Chandler, O Omodunbi, T Loganathan, S Kunhunny, D Sinha, M Sheppard, S Kelavkar, K Ng, A Ropun, L Kamuriwo, R Orath Prabakaran, E France, S Rashmi, D Mangion, C Constantin, S Markova, A Hardwick, J Borley, L De Michele Hock, T Lawrence, J Fletcher, K Netherton, R Spencer, H Palmer, M Soliman, S Leach, J Sharma, C Taylor, I Wahishi, A Fields, S Butler, J Hindle, E Watson, C Hewitt, C Cullen, D Hamill, Z Mellor, T Fluskey, V Hankin, A Keeling, R Durairaj, D Shackcloth, R Tangney, T Hlaing, V Sutton, J Ewing, C Patterson, H Ramadan, R Bellfield, U Hamid, M Hooley, R Ghulam, L Masters, W Gaba, O Quinn, M Tate, N Mohammed, S Sethuraman, L Alwis, K Bharaj, R Pattni, F Justin, M Chauhan, L Eldridge, S Mintias, J Palmones, C Holmes, L Guthrie, N Devitt, J Leonard, M Osborn, L Ball, A Steele, E Dodd, A Holloway, P Baker, I Penwarden, S Caine, S Clarke, L Dow, R Wynn-Williams, J Kennedy, A DeVeciana, P Mathieson, I Reckless, R Teal, U Schulz, G Ford, P Mccann, G Cluckie, G Howell, J Ayer, B Moynihan, R Ghatala, G Cloud, N Al-Samarrai, F Watson, T Adedoyin, N Chopra, L Choy, N Clarke, A Dainty, A Blight, J Selvarajah, W Smith, F Moreton, A Welch, D Kalladka, B Cheripelli, A Lush, S El Tawil, N Day, K Montgomery, H Hamilton, D Ritchie, S Ramachandra, K McLeish, B Badiani, M Abdul-Saheb, A Chamberlain, M Mpelembue, R Bathula, M Lang, J Devine, L Southworth, N Epie, E Owoyele, F Guo, A Oshodi, V Sudkeo, K Thavanesan, D Tiwari, C Ovington, E Rogers, R Bower, B Longland, O David, A Hogan, S Loganathan, C Cox, S Orr, M Keltos, K Rashed, B Williams-Yesson, J Board, S De Bruijn, C Vickers, S Board, J Allison, E Keeling, T Duckett, D Donaldson, C Barron, L Balian, T England, A Hedstrom, E Bedford, M Harper, E Melikyan, W Abbott, M Goldsworthy, M Srinivasan, I Mukherjee, U Ghani, A Yeomans, F Hurford, R Chapman, S Shahzad, N Motherwell, L Tonks, R Young, D Dutta, P Brown, F Davis, J Turfrey, M Obaid, B Cartwright, B Topia, J Spurway, C Hughes, S OConnell, K Collins, R Bakawala, K Chatterjee, T Webster, S Haider, P Rushworth, F Macleod, C Perkins, A Nallasivan, E Burns, S Leason, T Carter, S Seagrave, E Sami, S Parkinson, L Armstrong, S Mawer, G Darnbrook, C Booth, B Hairsine, S Williamson, F Farquhar, B Esisi, T Cassidy, B McClelland, G Mankin, M Bokhari, D Sproates, S Hurdowar, N Sukhdeep, S Razak, N Upton, A Hashmi, K Osman, K Fotherby, A Willberry, D Morgan, G Sahota, K Jennings-Preece, D Butler, K Kauldhar, F Harrington, A Mate, J Skewes, K Adie, K Bond, G Courtauld, C Schofield, L Lucas, A James, S Ellis, B Maund, L Allsop, C Brodie, E Driver, K Harris, M Drake, E Thomas, M Burn, A Hamilton, S Mahalingam, A Benford, D Hilton, A Misra, L Hazell, K Ofori, M Mathew, S Dayal, I Burn, D Bruce, R Burnip, R Hayman, P Earnshaw, P Gamble, S Dima, M Dhakal, G Rogers, L Stephenson, R Nendick, Y Pai, K Nyo, V Cvoro, M Couser, A Tachtatzis, K Ullah, R Cain, N Chapman, S Pound, S McAuley, D Hargroves, B Ransom, K Mears, K Griffiths, L Cowie, T Hammond, T Webb, I Balogun, H Rudenko, A Thomson, D Ceccarelli, A Gillian, E Beranova, A Verrion, N Chattha, N Schumacher, A Bahk, D Sims, R Tongue, M Willmot, C Sutton, E Littleton, J Khaira, S Maiden, J Cunningham, Y Chin, M Bates, K Ahlquist, J Breeds, T Sargent, L Latter, A Pitt Ford, T Levett, N Gainsborough, A Dunne, E Barbon, S Hervey, S Ragab, T Sandell, C Dickson, S Power, J Dube, N Evans, B Wadams, S Elitova, B Aubrey, T Garcia, J Mcilmoyle, C Dickinson, C Jeffs, J Howard, C Armer, J Frudd, A Potter, S Donaldson, D Collas, S Sundayi, L Denham, D Oza, M Bhandari, S Ispoglou, K Sharobeem, A Hayes, J Howard-Brown, S Shanu, S Billingham, G Howard, E Wood, V Pressly, P Crawford, H Burton, A Walters, J Marigold, R Said, C Allen, S Evans, S Egerton, J Hakkak, R Lampard, S Tsang, R Creeden, I Gartrell, F Price, J Pryor, A Hedges, L Moseley, L Mercer, E Warburton, D Handley, S Finlay, N Hannon, A Espanol, H Markus, D Chandrasena, J Sesay, D Hayden, H Hayhoe, J Macdonald, M Bolton, C Farron, E Amis, D Day, A Culbert, L Whitehead, S Crisp, J OConnell, E Osborne, R Beard, P Corrigan, L Mokoena, M Myint, R Krishnamurthy, A Azim, S Whitworth, A Nicolson, M Krasinska-Chavez, J Imam, S Chaplin, J Curtis, L Wood, A Byrne, C McGhee, A Smart, F Donaldson, J Blackburn, C Copeland, P Fitzsimmons, G Fletcher, A Manoj, P Cox, L Trainor, H Allsop, U Sukys, S Valentine, D Jarrett, K Dodsworth, M Wands, C Watkinson, W Golding, J Tandy, K Yip, C James, Y Davies, A Suttling, K Nagaratnam, N Mannava, N Haque, N Shields, K Preston, G Mason, K Short, G Uitenbosch, G Lumsdale, H Emsley, S Sultan, B Walmsley, D Doyle, A McLoughlin, L Hough, B Gregary, S Raj, A Maney, S Blane, G Gamble, A Hague, B Duran, R Whiting, M Harvey, J Homan, L Foote, L Graham, C Lane, L Kemp, J Rowe, H Durman, L Brotherton, N Hunt, A Whitcher, C Pawley, P Sutton, S Mcdonald, D Pak, A Wiltshire, J Balami, C Self, J Jagger, G Healey, M Crofts, A Chakrabarti, C Hmu, J Keshet-Price, G Ravenhill, C Grimmer, T Soe, I Potter, P Tam, M Langley, M Christie, J Irvine, A Joyson, F Annison, D Christie, C Meneses, V Taylor, J Furnace, H Gow, J Reid, Y Abousleiman, S Goshawk, J Purcell, T Beadling, S Collins, S Sangaralingham, E Munuswamy Vaiyapuri, M Landicho, Y Begum, S Mutton, J Lowe, I Wiggam, S Tauro, S Cuddy, B Wells, A Mohd Nor, N Persad, M Weinling, S Weatherby, D Lashley, A Pace, A Mucha, J Baker, M Marner, J Westcott, N Wilmshurst, D Chadha, M Fairweather, D Walstow, R Fong, M Krishnan, H Thompson Jones, C Lynda, C Clements, T Anjum, S Sharon, D Lynne, S Tucker, D Colwill, E Vasileiadis, A Parry, C Mason, M Holden, K Petrides, T Nishiyama, H Mehta, S Mumani, C Almadenboyle, S Carson, M Stirling, E Tenbruck, D Broughton, A Annamalai, D Tryambake, A Skotnicka, A Sigsworth, S Whitehouse, J Pagan, A Pusalkar, H Beadle, K Chan, P Dangri, A Asokanathan, A Rana, S Gohil, K Crabtree, A Cook, M Massyn, P Aruldoss, S Dabbagh, T Black, C Clarke, R Fennelly, L Nardone, V DiMartino, A Anthony, D Mead, M Tribbeck, B Affley, C Sunderland, E Young, L Goldenberg, P Wilkinson, L Abbott, R Nari, S Lock, A Shakhon, R Pereira, M DSouza, S Dunn, N Cron, A Mckenna, R Sivakumar, S Cook, J Ngeh, R Saksena, J Ketley-O'Donel, R Needle, E Chinery, L Howaniec, C Watchurst, R Erande, M Brezitski, N Passeron, E Elliott, N Oji, D Austin, A Banaras, C Hogan, T Corbett, M Kidd, G Hull, S Punekar, J Nevinson, H Penney, W Wareing, N Hayes, K Bunworth, L Connell, K Mahawish, G Drummond, N Sengupta, M Metiu, C Gonzalez, J Margalef, S Funnell, G Peters, I Chadbourn, H Proeschel, P Ashcroft, S Sharpe, P Cook, D Jenkinson, D Kelly, H Bray, G Gunathilagan, S Tilbey, S Abubakar, A Rajapakse, A Nasar, J Janbieh, L Otter, I Wynter, S Haigh, R Boulton, J Burgoyne, A Boulton, J Vassallo, A Hasan, L Orrell, S Qamar, D Leonard, E Hewitt, M Haque, J Awolesi, E Bradshaw, A Kent, A Hynes, E Nurse, S Raza, U Pallikona, B Edwards, G Morgan, H Tench, R Loosley, K Dennett, T Trugeon-Smith, D Robson, R Rayessa, A Abdul-Hamid, V Lowthorpe, K Mitchelson, E Clarkson, H Rhian, R Kirthivasan, J Topliffe, R Keskeys, F McNeela, E Bohannan, L Cooper, G Zachariah, F Cairns, T James, L Fergey, S Smolen, A Lyle, E Cannon, S Omer, S Mavinamane, S Meenakshisundaram, L Ranga, J Bate, M Hargreaves, S Dealing, S Amlani, G Gulli, M Hawkes-Blackburn, L Francis, S Holland, A Peacocke, J Amero, M Burova, O Speirs, S Brotheridge, S Al Hussayni, H Lyon, C Hare, J Featherstone, M Goorah, J Walford, D Rusk, D Sutton, F Patel, S Duberley, K Hayes, E Ahmed El Nour, S Dyer, E Temlett, J Paterson, S Honour, C Box, R Furness, E Orugun, H Crowther, R Glover, C Brewer, S Thornthwaite, M Sein, K Haque, L Bailey, E Gibson, L Brookes, K Rotchell, K Waltho, C Lindley, P Harlekar, C Culmsee, L Booth, J Ritchie, N Mackenzie, J Barker, M Haley, D Cotterill, L Lane, D Simmons, R Warinton, G Saunders, H Dymond, S Kidd, C Little, Y Neves-Silva, B Nevajda, M Villaruel, U Umasankar, A Man, N Gadi, N Christmas, R Ladner, R Rangasamy, G Butt, W Alvares, M Power, S Hagan, K Dynan, D Wilson, S Crothers, B Wroath, G Douris, D Vahidassr, B Gallen, C McGoldrick, M Bhattad, J Putteril, R Gallifent, E Makanju, M Lepore, C McRedmond, L Arundell, A Goulding, K Kawafi, P Jacob, L Turner, N Saravanan, L Johnson, D Morse, R Namushi, S Humphrey, M Salehin, S Tinsley, T Jones, L Garcia-Alen, L Kalathil, N Gautam, J Horton, J Meir, E Margerum, A Ritchings, K Amor, V Nadarajan, J Laurence, S Fung Lo, S Melander, P Nicholas, E Woodford, G McKenzie, V Le, J Crause, P OMahony, C Orefo, C McDonald, E Osikominu, G Appiatse, A Wardale, M Augustin, R Luder, M Bhargava, G Bhome, V Johnson, D Chesser, H Bridger, E Murali, A Burns, J Graham, M Duffy, E Pitcher, J Gaylard, J Newman, S Punnoose, S Oakley, V Murray, C Bent, R Walker, K Purohit, A Rees, S Besley, O Chohan, L Argandona, L Cuenoud, H Hassan, E Erumere, A OCallaghan, O Redjep, G Auld, P Gompertz, A Song, R Hungwe, H Kabash, T Tarkas, G Livingstone, F Butler, S Bradfield, L Gordon, J Schmit, A Wijewardane, C Medcalf, T Edmunds, R Wills, and C Peixoto
Subjects: Medicine
Abstract: Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.
Published: 2020
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33. International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale

Author: Amy S Paller, Emma Guttman-Yassky, Katrina Abuabara, Jonathan I Silverberg, Eric L Simpson, Lawrence F. Eichenfield, Robert Bissonnette, James Krueger, John E. Harris, Laura Dalfonso, Stephanie E Watkins, Julie M Crawford, and D Thaçi
Subjects: Medicine
Abstract: Introduction As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.Methods and analysis The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events.Ethics and dissemination TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals.Trial registration number NCT03661866, pre-results.
Published: 2020
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34. A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa

Author: Laura E. Levin, Catherine McCuaig, Anne W. Lucky, Kimberly D. Morel, Lawrence A. Schachner, Amy Huang, Harper N. Price, Irene Lara-Corrales, Moise L. Levy, Karen Wiss, Elena Pope, Phuong Khuu, Laura Kaplan, Jean Y. Tang, Kristen P. Hook, Amy S. Paller, Leslie Castelo-Soccio, Tor Shwayder, Kathleen Peoples, Marla N. Jahnke, Julie Powell, Susan J. Bayliss, Sharon A. Glick, John Browning, Gregory S. Phillips, Lawrence F. Eichenfield, Anna L. Bruckner, and Bret D. Augsburger
Subjects: medicine.medical_specialty, business.industry, Genetic counseling, Fluorescent Antibody Technique, Diagnostic test, Diagnostic concordance, Retrospective cohort study, Dermatology, Junctional epidermolysis bullosa (medicine), medicine.disease, Epidermolysis Bullosa Dystrophica, Interquartile range, Epidermolysis Bullosa Simplex, North America, Cohort, medicine, Humans, Epidermolysis bullosa, Epidermolysis Bullosa, Epidermolysis Bullosa, Junctional, business, Retrospective Studies
Abstract: BACKGROUND Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P
Published: 2022
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35. Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair

Author: Megan J. Riddle, Nicholas J Lawrence, Jakub Tolar, Sang Y Yun, Heather E. Stefanski, Bruce R. Blazar, Kelly Walton, Michael A. Linden, Elizabeth M. Sagatys, Jane Yuet Ching Hui, Jongphil Kim, Yan Xing, Harshani Lawrence, Brian C. Betts, John V. Kiluk, Marie C. Lee, Said M. Sebti, Kirsti Walker, Joseph Pidala, Jordan Reff, Claudio Anasetti, and Brent H. Koehn
Subjects: Graft Rejection, T cell, Article, Mice, Immune system, Animals, Humans, Transplantation, Homologous, Immunology and Allergy, Medicine, Pharmacology (medical), STAT5, Aurora Kinase A, Transplantation, Innate immune system, biology, business.industry, Innate lymphoid cell, GATA3, Janus Kinase 2, Immunity, Innate, Mice, Inbred C57BL, medicine.anatomical_structure, biology.protein, Cancer research, Th17 Cells, business
Abstract: Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. AJI-100 significantly reduces the frequency of skin-homing CLA(+) donor T cells, limiting allograft invasion and tissue destruction by T effectors. AJI-100 also suppresses pathogenic Th1 and Th17 cells in the spleen yet spares beneficial regulatory T cells (Tregs). We show dual JAK2/Aurora kinase A blockade enhances human type 2 innate lymphoid cell (ILC2) responses, which are capable of tissue repair. ILC2 differentiation mediated by GATA3 requires STAT5 phosphorylation (pSTAT5) but is opposed by STAT3. Further, we demonstrate that Aurora kinase A activation correlates with low pSTAT5 in ILC2s. Importantly, AJI-100 maintains pSTAT5 levels in ILC2s by blocking Aurora kinase A and reduces interference by STAT3. Therefore, combined JAK2/Aurora kinase A inhibition is an innovative strategy to merge immune suppression with tissue repair after transplantation.
Published: 2022
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36. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C 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Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, 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Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M 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C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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37. Prevalence and Predictors of Household Food Insecurity and Supplemental Nutrition Assistance Program Use in Youth and Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study

Author: Beth A. Reboussin, Catherine Pihoker, Dana Dabelea, Jason A. Mendoza, Anna Bellatorre, Christine B. Turley, Beth Loots, Elizabeth T. Jensen, Jean M. Lawrence, Edward A. Frongillo, Faisal Malik, Elizabeth J. Mayer-Davis, Katherine A. Sauder, and Angela D. Liese
Subjects: Advanced and Specialized Nursing, Research design, Type 1 diabetes, education.field_of_study, business.industry, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, medicine.disease, Logistic regression, Diabetes mellitus, Internal Medicine, medicine, Epidemiology/Health Services Research, Young adult, business, education, Medicaid, Demography
Abstract: OBJECTIVE To assess the prevalence of household food insecurity (HFI) and Supplemental Nutrition Assistance Program (SNAP) participation among youth and young adults (YYA) with diabetes overall and by type, and sociodemographic characteristics. RESEARCH DESIGN AND METHODS The study included participants with youth-onset type 1 diabetes and type 2 diabetes from the SEARCH for Diabetes in Youth study. HFI was assessed using the 18-item U.S. Household Food Security Survey Module (HFSSM) administered from 2016 to 2019; three or more affirmations on the HFSSM were considered indicative of HFI. Participants were asked about SNAP participation. We used χ2 tests to assess whether the prevalence of HFI and SNAP participation differed by diabetes type. Multivariable logistic regression models were used to examine differences in HFI by participant characteristics. RESULTS Of 2,561 respondents (age range, 10–35 years; 79.6% ≤25 years), 2,177 had type 1 diabetes (mean age, 21.0 years; 71.8% non-Hispanic White, 11.8% non-Hispanic Black, 13.3% Hispanic, and 3.1% other) and 384 had type 2 diabetes (mean age, 24.7 years; 18.8% non-Hispanic White, 45.8% non-Hispanic Black, 23.7% Hispanic, and 18.7% other). The overall prevalence of HFI was 19.7% (95% CI 18.1, 21.2). HFI was more prevalent in type 2 diabetes than type 1 diabetes (30.7% vs. 17.7%; P < 0.01). In multivariable regression models, YYA receiving Medicaid or Medicare or without insurance, whose parents had lower levels of education, and with lower household income had greater odds of experiencing HFI. SNAP participation was 14.1% (95% CI 12.7, 15.5), with greater participation among those with type 2 diabetes compared with those with type 1 diabetes (34.8% vs. 10.7%; P < 0.001). CONCLUSIONS Almost one in three YYA with type 2 diabetes and more than one in six with type 1 diabetes reported HFI in the past year—a significantly higher prevalence than in the general U.S. population.
Published: 2022
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38. Role of Bioactivation Reactions in Chemically Induced Nephrotoxicity

Author: Lawrence H. Lash
Subjects: chemistry.chemical_classification, Kidney, urogenital system, Chemistry, Pharmacology, Nephrotoxicity, Chemically Induced Toxicity, chemistry.chemical_compound, Enzyme, medicine.anatomical_structure, medicine, Xenobiotic, human activities, Drug toxicity
Abstract: Kidneys express a diverse array of enzymes that can catalyze the bioactivation of many drugs and xenobiotics. The kidneys are particularly susceptible to chemically induced toxicity because of their basic physiology and biochemistry. The article discusses the role of bioactive reactions in chemically induced nephrotoxicity. Keywords: nephrotoxicity; xenobiotics; kidney; bioactive reactions; drug toxicity
Published: 2022
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39. Extracorporeal photopheresis (ECP) improves overall survival in the treatment of steroid refractory acute graft-versus-host disease (SR aGvHD)

Author: H. Kent Holland, Asad Bashey, Xu Zhang, Lawrence E. Morris, Chloe Farnham, Melhem Solh, and Scott R. Solomon
Subjects: medicine.medical_specialty, Transplantation, business.industry, Cell Biology, Hematology, Gastroenterology, Internal medicine, Extracorporeal Photopheresis, Acute graft versus host disease, Overall survival, Molecular Medicine, Immunology and Allergy, Medicine, business, Steroid refractory
Published: 2022
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40. Work-related and nonwork stressors, PTSD, and psychological distress: Prevalence and attributable burden among Australian police and emergency services employees

Author: David Lawrence, Wavne Rikkers, Jennifer Bartlett, Anthony D. LaMontagne, and Michael J. Kyron
Subjects: medicine.medical_specialty, Social Psychology, PsycINFO, Psychological Distress, Work related, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Prevalence, Humans, Medicine, 030212 general & internal medicine, Psychiatry, business.industry, Stressor, Australia, Odds ratio, Mental health, Police, 030227 psychiatry, Clinical Psychology, Distress, Attributable risk, Occupational stress, business, Stress, Psychological
Abstract: OBJECTIVE Police and emergency services personnel are at an increased risk of developing mental health issues. We sought to compare patterns of exposure to work-related and nonwork stressors and associations with posttraumatic stress symptoms and psychological distress among police and emergency services employees. METHOD A total of 14,868 employees from 33 ambulance, fire and rescue, police, and state emergency service agencies around Australia participated in a survey to assess the prevalence of exposure to work-related and nonwork stressors, and the prevalence of mental health conditions. Associations between work and nonwork stressors and mental health problems were estimated using logistic regression models and population attributable risk (PAR) percentages. RESULTS Traumatic events experienced while working in the police and emergency services sector were the most frequently reported stressor (51%). Stressful events experienced at work in the sector were associated with significantly higher levels of suspected posttraumatic stress symptoms (odds ratio = 4.5, PAR = 65%) and high psychological distress (odds ratio = 2.5, PAR = 40%) compared to stressors experienced away from the sector. CONCLUSIONS Stressors experienced at work are a risk factor for developing posttraumatic stress symptoms and distress in the sector. Organizations should have comprehensive policies and programs to help prevent the development of mental health problems and to support personnel who develop mental health problems. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Published: 2022
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41. Traumatic injury to peripheral nerves

Author: Lawrence R. Robinson
Subjects: medicine.medical_specialty, Time Factors, Electrodiagnosis, Physiology, Central nervous system, Neural Conduction, Electromyography, Models, Biological, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Peripheral nerve, Peripheral Nerve Injuries, Physiology (medical), Animals, Medicine, Humans, Peripheral Nerves, Muscle, Skeletal, Nerve Transfer, Radial nerve, Needle electromyography, Plexus, medicine.diagnostic_test, business.industry, Peripheral Nervous System Diseases, Recovery of Function, medicine.disease, Prognosis, Peripheral, Electrophysiology, medicine.anatomical_structure, Traumatic injury, Anesthesia, Peripheral nervous system, Wounds and Injuries, Upper limb, Sciatic nerve, Neurology (clinical), business, Neuroscience, Penetrating trauma, Sensory nerve
Abstract: Publisher Summary This chapter discusses the epidemiology and classification of traumatic peripheral nerve injuries, the effects of these injuries on nerve and muscle, and how electrodiagnosis is used to help classify the injury. Traumatic injury to peripheral nerves results in considerable disability across the world. In peacetime, peripheral nerve injuries result commonly from motor vehicle accident trauma and less commonly from penetrating trauma, such as falls and industrial accidents. If plexus and root injuries are also included, the incidence is about 5%. In the upper limb, the nerve injured most commonly is the radial nerve, followed by the ulnar and median nerves. Lower limb peripheral nerve injuries are less common, and the sciatic nerve is injured most frequently, followed by the peroneal and rarely the tibial or femoral nerves. Peripheral nerve injuries may be seen in isolation, but they also often accompany central nervous system (CNS) trauma. Peripheral nerve injuries have significant impact, as they impede the recovery of function and return to work. There is also a risk of secondary disability from falls, fractures, or other injuries.
Published: 2022
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42. High epileptiform discharge burden predicts delayed cerebral ischemia after subarachnoid hemorrhage

Author: Jonathan Elmer, Sahar F. Zafar, Manohar Ghanta, Wei-Long Zheng, Valdery Moura Junior, Jennifer A. Kim, M. Brandon Westover, Jin Jing, Aman B. Patel, Eric Rosenthal, Emily J. Gilmore, and Lawrence J. Hirsch
Subjects: Moderate to severe, Periodicity, medicine.medical_specialty, Subarachnoid hemorrhage, Ischemia, Electroencephalography, 050105 experimental psychology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Retrospective analysis, Humans, 0501 psychology and cognitive sciences, cardiovascular diseases, Retrospective Studies, Receiver operating characteristic, medicine.diagnostic_test, business.industry, 05 social sciences, Cerebral Infarction, Subarachnoid Hemorrhage, medicine.disease, Sensory Systems, nervous system diseases, Neurology, Cardiology, Biomarker (medicine), Neurology (clinical), business, Complication, 030217 neurology & neurosurgery
Abstract: Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.
Published: 2022
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43. Bispecific antibodies for the treatment of breast cancer

Author: Patrick M. Dillon, Lawrence G Lum, and Jogender Tushir-Singh
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, T-Lymphocytes, Clinical Biochemistry, Estrogen receptor, Breast Neoplasms, Disease, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Drug Discovery, Antibodies, Bispecific, medicine, Tumor Microenvironment, Humans, Pharmacology, business.industry, Cancer, Immunotherapy, medicine.disease, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, Female, business
Abstract: Introduction There are more than two dozen bispecific antibodies (BsAbs) in development with a variety of designs which are relevant to breast cancer. The field of BsAbs for breast cancer includes agents that co-direct immune recognition of the cancer cell, target unique cancer antigens, and target the microenvironment. BsAbs are being developed for use as antibody-drug conjugates and as homing signals for engineered T-cells. Areas covered This review covers potential targets for bispecific antibodies, agents in pre-clinical development, agents in clinical trials, combinatorial therapies, and future directions. Expert opinion There is no BsAb approval expected for breast cancer in the near term, but late-stage trials are underway. Future BsAb roles in breast cancer are possible given unmet needs in estrogen receptor+ disease, residual disease, and de-escalating chemotherapy use. The HER2+ space shows hints of success for BsAbs, but is already crowded. Areas of unmet need still exist.
Published: 2023

44. Alternative cause for hypoglycaemia in insulin-treated diabetes mellitus

Author: Viraj Parmar, Vasanth Sritharan, Christopher Lawrence, and Archana Dhere
Subjects: medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, 030209 endocrinology & metabolism, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, medicine, Humans, Insulin, 030212 general & internal medicine, Insulinoma, Aged, Reactive hypoglycemia, C-Peptide, business.industry, nutritional and metabolic diseases, Hydroxychloroquine, General Medicine, medicine.disease, Hypoglycemia, Discontinuation, Pancreatic Neoplasms, Diabetes Mellitus, Type 2, Prednisolone, Gastrectomy, Female, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud’s disease, previous breast cancer, Barrett’s oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.
Published: 2023

45. Enhancing Mirror Therapy via Scaling and Shared Control: A Novel Open-Source Virtual Reality Platform for Stroke Rehabilitation

Author: Daniel Kortemeyer, Lawrence Glista, Thomas E. Augenstein, and Chandramouli Krishnan
Subjects: Rehabilitation, Computer science, business.industry, medicine.medical_treatment, Process (computing), Virtual reality, Computer Graphics and Computer-Aided Design, Article, Human-Computer Interaction, Computer graphics, Software, Human–computer interaction, Scalability, Data_FILES, medicine, business, Functional movement, Mirroring
Abstract: Mirror therapy is increasingly used in stroke rehabilitation to improve functional movements of the affected limb. However, the extent of mirroring in conventional mirror therapy is typically fixed (1:1) and cannot be tailored based on the patient’s impairment level. Further, the movements of the affected limb are not actively incorporated in the therapeutic process. To address these issues, we developed an immersive VR system using HTC Vive and Leap Motion, which communicates with our free and open-source software environment programmed using SteamVR and the Unity 3D gaming engine. The mirror therapy VR environment was incorporated with two novel features: (1) scalable mirroring and (2) shared control. In the scalable mirroring, mirror movements were programmed to be scalable between 0 and 1, where 0 represents no movements, 0.5 represents 50% mirroring, and 1 represents 100% mirroring. In shared control, the contribution of the mirroring limb to the movements was programmed to be scalable between 0 to 1, where 0 represents 100% contribution from the mirroring limb (i.e., no mirroring), 0.5 represents 50% of movements from the mirrored limb and 50% of movements from the mirroring limb, and 1 represents full mirroring (i.e., no shared movements). Validation experiments showed that these features worked appropriately. The proposed VR-based mirror therapy is the first fully developed system that is freely available to the rehabilitation science community. The scalable and shared control features can diversify mirror therapy and potentially augment the outcomes of rehabilitation, although this needs to be verified through future experiments.
Published: 2023

46. Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons

Author: Ryan M. Ames, Akshay Bhinge, Seema C. Namboori, Patricia Thomas, Lawrence W. Stanton, Alessandro Rosa, Lawrence O. Garrett, Craig R. G. Willis, and Sophie Hawkins
Subjects: developmental pathways, Induced Pluripotent Stem Cells, SOD1, Gene regulatory network, Biology, Biochemistry, Article, TGFβ, Superoxide Dismutase-1, Interneurons, Transforming Growth Factor beta, C9orf72, Genetics, medicine, Humans, Gene Regulatory Networks, Amyotrophic lateral sclerosis, Induced pluripotent stem cell, ALS, iPSC, networks, single-cell RNA-seq, spinal MN, Motor Neurons, Gene Expression Profiling, Amyotrophic Lateral Sclerosis, Neurodegeneration, Cell Biology, Motor neuron, medicine.disease, medicine.anatomical_structure, Gene Expression Regulation, nervous system, Nerve Degeneration, Single-Cell Analysis, Neuroscience, Signal Transduction, Developmental Biology, Transforming growth factor
Abstract: Summary Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by the loss of motor neurons. We utilized single-cell transcriptomics to uncover dysfunctional pathways in degenerating motor neurons differentiated from SOD1 E100G ALS patient-derived induced pluripotent stem cells (iPSCs) and respective isogenic controls. Differential gene expression and network analysis identified activation of developmental pathways and core transcriptional factors driving the ALS motor neuron gene dysregulation. Specifically, we identified activation of SMAD2, a downstream mediator of the transforming growth factor β (TGF-β) signaling pathway as a key driver of SOD1 iPSC-derived motor neuron degeneration. Importantly, our analysis indicates that activation of TGFβ signaling may be a common mechanism shared between SOD1, FUS, C9ORF72, VCP, and sporadic ALS motor neurons. Our results demonstrate the utility of single-cell transcriptomics in mapping disease-relevant gene regulatory networks driving neurodegeneration in ALS motor neurons. We find that ALS-associated mutant SOD1 targets transcriptional networks that perturb motor neuron homeostasis., Highlights • Single-cell transcriptomic analysis of SOD1 E100G ALS iPSC-derived motor neurons • Mapping an ALS-relevant transcriptional network • Upregulation of developmental programs in familial and sporadic ALS motor neurons • Inhibition of TGFβ pathway improves SOD1 ALS iPSC-derived motor neuron survival, In this article, Bhinge and colleagues use single-cell transcriptomics to analyze degenerating motor neurons (MNs) differentiated from SOD1 E100G ALS patient-derived iPSCs. Using network analysis, they uncover upregulation of developmental pathways and TGFβ activation in familial and sporadic ALS MNs. Importantly, they find that inhibition of TGFβ signaling leads to improved survival of SOD1 ALS iPSC-derived MNs.
Published: 2021
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47. Staff perceptions of family access and visitation policies in Australian and New Zealand intensive care units: The WELCOME-ICU survey

Author: Edward Litton, Kim Lawrence, Paul J Young, Shakira Spiller, Cath Townsend, Chris Waite, Lewis T Campbell, Elizabeth Yarad, Nadia Badawi, Joanne Hallam, Mahesh Ramanan, Allison Bone, Elizabeth Doyle, Maité Garrouste-Orgeas, Sunil Sane, Elaine McGlion, Rand Butcher, Natalie Soar, Phillipa Hillard, Sheena Tom, Mandy Stanley, Fiona Coyer, Amanda O’Donnell, Alexis Tabah, Janet Ferrier, Gail Hanger, Sharon Waterson, J. L. Smith, Tor Topping, Kim Bonnici, Abby McClintock, Jenny Dennett, Rachel L. Bailey, Neeraj Bhadange, Kirsty Masters, Nathalie Ssi Yan Kai, Amy Hartley, Emer Slattery, Annamaria Palermo, Sandra Colica, and Sue Cossar
Subjects: medicine.medical_specialty, Emergency Nursing, Burnout, Critical Care Nursing, law.invention, law, Surveys and Questionnaires, Intensive care, Health care, Humans, Medicine, Family, Burnout, Professional, Staff perceptions, business.industry, Australia, Workload, Visitors to Patients, Intensive care unit, Family nursing, Intensive Care Units, Family member, Policy, Family medicine, business, New Zealand
Abstract: Background: Family-centred critical care recognises the impact of a loved one's critical illness on his relatives. Open visiting is a strategy to improve family satisfaction and psychological outcomes by permitting unrestricted or less restricted access to visit their family member in the intensive care unit (ICU). However, increased family presence may result in increased workload and a risk of burnout for ICU staff. Objectives: The objective of this study was to evaluate ICU staff perceptions regarding visiting hours and family access in Australian and New Zealand ICUs. Secondary outcomes included an evaluation of current visiting policies, witnessed events in ICUs, and barriers to implementing open visiting policies. Design: A web-based survey open to all healthcare workers in Australia and New Zealand ICUs was distributed through local, state-based, and national critical care networks. Open visiting was defined as ICUs open for visiting >14 h per day. Main results: We received 1255 valid responses. Most respondents were nurses (n = 930, 74.1%) with a median critical care experience of 10 y. Most worked in open visiting ICUs (n = 749, 59.7%). Reported visiting hours varied greatly with a median of 20 h per day (interquartile range: 10–24 h). Open visiting was perceived as beneficial for the relatives, but less so for patients and staff (relatives: n = 845, 67.3%, patients: n = 561, 44.7%, staff: n = 257, 20.5%, p < 0.0001). Respondents from closed visiting units and nurses identified more risks from open visiting than other professional groups. Generally, staff preferred not to change from their current practice. Conclusion: We report that staff perceived open visiting as beneficial for relatives, but also identified risks to themselves, including increased workload, a risk of burnout, and a risk of occupational violence. Reluctance to change highlights the importance of addressing staff perceptions when implementing an open visiting policy.
Published: 2022
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48. The Tōhoku Theater Project in Postdisaster Japan: An Exemplar for Addressing Community Mental Health in the Context of Disaster

Author: Lawrence H. Yang, Tsuyoshi Akiyama, Kathleen M. Pike, Setsu Hanasaki, Tahilia J. Rebello, Nao Suzuki, Phyllis Kaufman, Ryoko Narita-Ohtaki, Bryan Doerries, Seiji Yasumura, and Elizabeth Magill
Subjects: Coping (psychology), medicine.medical_specialty, business.industry, media_common.quotation_subject, Public health, COVID-19, Context (language use), Empathy, Public relations, The arts, Mental health, Disasters, Psychiatry and Mental health, Mental Health, Japan, Pandemic, Earthquakes, medicine, Humans, Psychological resilience, business, Psychology, Pandemics, media_common
Abstract: The Tōhoku Theater Project was completed 2 years after the natural and nuclear disasters in Tōhoku, Japan, on March 11, 2011. It employed the dramatic arts to support the healing process, promote resilience, and increase dialogue and understanding about mental health among individuals who were directly affected by the disasters. The four performances fostered important discussions regarding the psychological impact of the Tōhoku disasters. Participants (N=143) found the theater performance effective at facilitating discussion, increasing empathy, and enhancing mental health knowledge, coping, and resilience. The performances provided critical information about access to services; many participants reported that they had not known where to seek help for mental health prior to their involvement with the Tōhoku Theater Project. Lessons learned may inform community-based strategies that promote mental health and healing in the wake of the COVID-19 pandemic and other public health disasters.
Published: 2022
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49. Factors Associated With Chronic De Novo Post-Coronavirus Disease Gastrointestinal Disorders in a Metropolitan US County

Author: Christopher Vélez, Mary Paz, Casey Silvernale, Lawrence W. Stratton, Braden Kuo, Kyle Staller, Esteban Barreto, Josselyn Vergara Cobos, Kelly L. Buchanan, Taylor Boyd, Anshuman C. Desai, Shreya Chablaney, Ingrid Guerrero López, and Joseph R. Betancourt
Subjects: medicine.medical_specialty, Hepatology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Public health, Gastroenterology, Ethnic group, medicine.disease, Metropolitan area, Underserved Population, Internal medicine, Pandemic, medicine, business, Socioeconomic status, Irritable bowel syndrome
Abstract: The first coronavirus disease 2019 (COVID-19) pandemic surge harshly impacted the medically underserved populations of the urbanized northeastern United States. Severe acute respiratory syndrome coronavirus 2 virions infect the gastrointestinal (GI) tract, and GI symptoms are common during acute infection.1 Post-COVID syndromes increasingly are recognized as important public health considerations.2 Postinfectious disorders of gut-brain interaction (DGBIs; formerly known as functional gastrointestinal disorders) can occur after enteric illness; the COVID-19 pandemic is anticipated to provoke DGBI development3 within a rapidly evolving post-COVID framework of illness. Here, we evaluate factors associated with DGBI-like post-COVID gastrointestinal disorders (PCGIDs) in our hospital's surrounding communities comprised predominantly of racial/ethnic minorities and those of reduced socioeconomic status.
Published: 2022
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50. To what degree are review outcomes aligned for new active substances (NASs) between the European Medicines Agency and the US Food and Drug Administration? A comparison based on publicly available information for NASs initially approved in the time period 2014 to 2016

Author: Thomas Christian Kühler, Magda Bujar, Neil McAuslane, and Lawrence Liberti
Subjects: Medicine
Abstract: Objective To compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.Design Using publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.Results In 2014–2016, 115 NASs were approved by EMA or FDA or both; 74/115 were new chemical entities and 41 new biological/biotechnology entities; 82/115 were approved by both agencies, 24 only by FDA and nine only by EMA. Simultaneous submission occurred for 52/115; 13/52 received expedited review by both agencies and 18 only by FDA; 8/52 received conditional approval from both agencies, 2/52 only from FDA and 1/52 only from EMA; 17/52 were designated as orphans by both agencies and 10/52 by FDA only; 31/52 indications were approved as submitted and 21 changed by EMA and 29/46 were approved as submitted (six not assessed) and 17/46 changed by FDA. Median FDA review timelines were 319 days compared with 409 days for EMA.Conclusions There was general agreement in EMA / FDA conditional approvals. FDA used expedited pathways and orphan designation more often than EMA, suggesting stricter EMA criteria or definitions for these designations or less flexible processes. Despite consistency in submitted indications, there was lack of concordance in approved indications, which should be further investigated. FDA review times are faster because of a wider range of expedited pathways and the two-step EMA process; this may change with recent revisions to EMA accelerated assessment guidelines and the launch of Priority Medicines.
Published: 2019
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