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1. Care Management for Serious Mental Illness: A Systematic Review and Meta-Analysis

Author: Clifton M. Chow, Marissa P Caan, Miriam C. Tepper, Clara H Kim, Christopher T Lim, and H. Stephen Leff
Subjects: Adult, medicine.medical_specialty, business.industry, Mental Disorders, Case management, Mental illness, medicine.disease, Psychiatry and Mental health, Meta-analysis, Health care, Ambulatory Care, Humans, Medicine, business, Psychiatry
Abstract: Persons with serious mental illness face adverse psychiatric and medical outcomes, and their care is associated with a large burden of health care costs. Care management, in which assessment, care planning, and care coordination are provided, is a common model of support, yet the evidence supporting its use among psychiatric populations is mixed. A systematic review and a meta-analysis were undertaken to determine the impact of care management on clinical outcomes, acute care utilization, cost, and satisfaction among adults with serious mental illness.A multidatabase literature search was performed. Articles were included if they compared standard outpatient care plus care management with standard outpatient care alone for adults with serious mental illness and reported on one or more predefined outcomes. Randomized controlled trials (RCTs) and other study designs were permitted for inclusion in the systematic review. The meta-analysis included only RCTs.For the systematic review, 34 articles representing 28 unique studies were included. Fifteen of these articles, representing 12 unique studies, were included in the meta-analysis, which indicated that care management was associated with small, statistically significant improvements in psychiatric symptoms, overall quality of life (QOL), and mental QOL (Hedges' g range 0.13-0.26). In addition, care management was associated with a small, statistically significant reduction in inpatient psychiatric hospital days (Hedges' g=0.16, p=0.02).Care management is associated with fewer psychiatric symptoms and greater QOL for persons with serious mental illness. Further work is needed to determine which components of the intervention are associated with effectiveness.
Published: 2022
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2. Endoscopic Removal of a Fecalith or Fecomucolith in a Rectal Stump or Pouch

Author: Asiri Arachchi, James T. Lim, Evie Yeap, Ratheesraj Ratinam, Zeev Duieb, and Yeng Kwang Tay
Subjects: fecalith, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Gastroenterology, Colonoscopy, RC799-869, Diseases of the digestive system. Gastroenterology, gastrointestinal endoscopy, Polypectomy snare, Surgery, Rectal stump, colonoscopy, Technical Note, Medicine, Examination Under Anesthesia, Pouch, business, Biopsy forceps, Gastrointestinal endoscopy
Abstract: Fecaliths or fecomucoliths can form in rectal stumps after a Hartmann procedure or in a coloneovaginal conduit. They can cause significant distress to the patient by causing symptoms such as discharge and odor. We describe a novel and effective method of endoscopic obliteration and removal where other techniques such as removal during examination under anesthesia or serial enemas have failed. By using a combination of hydrodissection with a saline injector gun and biopsy forceps and a polypectomy snare to break down the fecomucolith or fecalith, this troublesome problem can be resolved endoscopically. Successful removal of the fecalith/fecomucolith and resolution of the symptoms for the patients were achieved. No complications are reported. We describe an effective and novel method for endoscopic removal of fecaliths and fecomucoliths.
Published: 2021

3. 20 Comparison of Six Frailty Screening Tools in Patients Aged 65+ with An Arm Fragility Fracture

Author: Mark Mullee, Shihua Zhu, Guiqing Lily Yao, C Russel, T Lim, S Tilley, Mark Baxter, Kinda Ibrahim, and Helen C. Roberts
Subjects: Aging, medicine.medical_specialty, Fragility fracture, Life style, business.industry, Hip region, General Medicine, Patient referral, Physical therapy, Medicine, Frail elderly, Screening tool, In patient, Fresh frozen plasma, Geriatrics and Gerontology, business
Abstract: Introduction Frailty is associated with an increased risk of falling and fracture, but not routinely assessed in fracture clinic. Early identification and management of frailty among older people with arm fragility fracture could help avoid further falls and fractures, especially of the hip. We evaluated the feasibility of assessing frailty in a busy fracture clinic. Methods People aged 65+ years with an arm fracture in one acute trust were recruited. Frailty was assessed in fracture clinics using six tools: Fried Frailty Phenotype (FFP), FRAIL scale, PRISMA-7, electronic Frailty Index (e-FI), Clinical Frailty Score (CFS), and Study of Osteoporotic Fracture (SOF). The sensitivity and specificity of each tool was compared against FFP as a reference. Participants identified as frail by 2+ tools were referred for Comprehensive Geriatric Assessment (CGA). Results 100 patients (mean age 75 years±7.2; 20 men) were recruited. Frailty prevalence was 9% (FRAIL scale), 13% (SOF), 14% (CFS > 6), 15% (FFP; e-FI > 0.25), and 25% (PRISMA-7). Men were more likely to be frail than women. Data were complete for all assessments and completion time ranged from one minute (PRISMA-7; CFS) to six minutes for the FFP which required most equipment. Comparing with FFP, the most accurate instrument for stratifying frail from non-frail was the PRISMA-7 (sensitivity = 93%, specificity = 87%) while the remaining tools had good specificity (range 93%–100%) but average sensitivity (range 40%–60%). Twenty patients were eligible for CGA. Five had recently had CGA and 11/15 referred were assessed. CGA led to 3–6 interventions per participant including medication changes, life-style advice, investigations, and onward referrals. Conclusion It was feasible to assess frailty in fracture clinic and to identify patients who benefitted from CGA. Frailty prevalence was 9%—25% depending on the tool used and was higher among men. PRISMA-7 could be a practical tool for routine use in fracture clinics.
Published: 2021
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4. Differences in anterior cruciate ligament injury risk factors between female dancers and female soccer players during single- and double-leg landing

Author: S.-T. Lim, Ji-Hoon Cho, E.-O. Cho, Keun-Ok An, and B.-O. Lim
Subjects: medicine.medical_specialty, biology, Anterior cruciate ligament, Repeated measures design, 030209 endocrinology & metabolism, 030229 sport sciences, musculoskeletal system, medicine.disease, biology.organism_classification, ACL injury, Trunk, 03 medical and health sciences, Vertical jump, Valgus, 0302 clinical medicine, Physical medicine and rehabilitation, medicine.anatomical_structure, medicine, Injury risk, Orthopedics and Sports Medicine, Ground reaction force, Psychology, human activities
Abstract: Summary Purpose The purpose of this study was to compare anterior cruciate ligament (ACL) injury risk factors between female dancers and female soccer players during single- and double-leg drop landing vertical jump tasks. Methods Fifteen elite female soccer players and 45 professional female dancers (15 ballet, 15 modern, and 15 Korean dancers) were recruited to participate in this study. ACL injury risk factors were obtained from motion and ground reaction force data. Two-way repeated measure of analyses of variance (participant groups and landing tasks, 4 × 2) were used. Results The female dancers landed with a significantly lower trunk flexion, trunk external rotation, knee external rotation, and knee valgus moment than the female soccer players. In addition, the single-leg drop landing task demonstrated higher trunk external rotation and knee valgus moment than the double-leg drop landing vertical jump task. The female dancers had lower ACL injury risk factors than the female soccer players during landing tasks. Conclusion The single-leg drop landing task is statistically correlated with ACL injury risk factors compared with double-leg drop landing vertical jump task in all groups.
Published: 2021
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5. Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh

Author: Mazharul Islam, Ghausia Begum, Tahrima Arman Tusty, Nushrat Jahan Dity, Shaoli Sarkar, Marc Woodbury-Smith, Hosneara Akter, Md. Atikur Rahaman, Mohammed Uddin, Bakhrom K. Berdeiv, Reem Abdel Hameid, Mohammad Basiruzzaman, K. M. Furkan Uddin, Sharmin Jahan, Darren D. O’Rielly, Elaine T. Lim, Mohammed Nazmul Ahsan, A.H.M. Nurun Nabi, Stephen W. Scherer, Mohammad Shahnoor Hossain, Dimitri J. Stavropoulos, Nasna Nassir, and Muhammad Sougatul Islam
Subjects: 0301 basic medicine, Population, Case Report, 030105 genetics & heredity, Biology, QH426-470, Compound heterozygosity, XY gonadal dysgenesis, 03 medical and health sciences, symbols.namesake, medicine, Genetics, education, Molecular Biology, Gene, Genetics (clinical), Exome sequencing, Sanger sequencing, education.field_of_study, Genetic heterogeneity, Mucolipidosis, Disease genetics, medicine.disease, 030104 developmental biology, symbols, Medicine, Medical genomics
Abstract: Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet–Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.
Published: 2021

6. Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Author: Eileen Poon, Miriam Tao, Nagavalli Somasundaram, Jason Yongsheng Chan, Peter Martin, Maica Jd Yunon, Shu Q Toh, Cindy Lim, Mohamad Farid, Soon T Lim, Tiffany Tang, and Sean X Yan
Subjects: medicine.medical_specialty, medicine.medical_treatment, Neutropenia, Lymphoma, T-Cell, Gastroenterology, Article, Dexamethasone, Carboplatin, chemistry.chemical_compound, Refractory, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, T-cell lymphoma, Humans, Ifosfamide, Etoposide, Chemotherapy, business.industry, Hematology, Triazoles, medicine.disease, Hydrazines, chemistry, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937).
Published: 2020

7. A Psychiatric Residency in the Era of COVID-19: A Bionian Perspective

Author: Marissa P. Caan, Zachary B Harris, and Christopher T Lim
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Context (language use), Betacoronavirus, Health care, Pandemic, medicine, Humans, Baseline (configuration management), Psychiatry, Pandemics, SARS-CoV-2, business.industry, Perspective (graphical), COVID-19, Internship and Residency, General Medicine, Group dynamic, Group Processes, Leadership, Hospital system, Coronavirus Infections, business, Psychology
Abstract: Coronavirus disease 2019 (COVID-19) is currently ravaging health systems across the world. Psychiatric trainees are at risk of exposure to patients with COVID-19 given their clinical roles in emergency and inpatient psychiatric settings. This article represents a case study of group dynamics in which we reflect on our own experience as psychiatric residents at a Boston-area hospital system in the era of COVID-19 and apply Wilfred Bion's concepts of the “work group” and the “basic assumption group” processes of group operation. We assess dynamics between trainees and administrative leadership both at baseline and in the current pandemic. Since navigation through crises is more effective if group leadership recognizes and responds to basic assumption behaviors, we propose suggestions to enable health system administration to successfully lead health care organizations through periods of societal turmoil. We posit that these principles apply across settings, specialties, and provider types. In addition, we use our observations to indicate future directions for expanding Bion's theories in the contemporary context.
Published: 2020
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8. Barriers and facilitators towards colonoscopy: a qualitative systematic review

Author: Choon Seng Chong, Kia T Lim, Glenn M Decruz, Cheng Han Ng, Ker-Kan Tan, Tian Zhi Lim, and Kamala M. Devi
Subjects: Cancer Research, medicine.medical_specialty, Epidemiology, Colorectal cancer, Health Personnel, Psychological intervention, MEDLINE, Colonoscopy, CINAHL, PsycINFO, 03 medical and health sciences, 0302 clinical medicine, Humans, Mass Screening, Medicine, 030212 general & internal medicine, Early Detection of Cancer, Physician-Patient Relations, Modalities, medicine.diagnostic_test, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Family medicine, Personal experience, Colorectal Neoplasms, business
Abstract: OBJECTIVES Colonoscopy is integral in the early detection of colorectal cancer (CRC), be it for screening, diagnostic or therapeutic intentions. Despite the presence of multiple screening modalities, colonoscopy remains integral in providing a definitive CRC diagnosis. However, uptake rates remain low worldwide with minimal understanding towards stakeholders' perspectives. This systematic review is the first to outline the barriers and facilitators faced by providers and patients in receiving colonoscopy specifically. METHODS Using PRISMA guidelines, our systematic review consolidates findings from Medline, Embase, CINAHL, PsycINFO and Web of Science Core collection. All perceptions of healthcare providers and screening participants aged 45 and above towards colonoscopy were included. RESULTS Forty-five articles were included in our review. Five major analytical themes were identified - procedural perceptions, personal experiences, thoughts and concerns, societal influences, doctor-patient relationship and healthcare system. The discrepancies in knowledge between patients and providers have evidently reduced in the present decade, potentially attributable to the rising influence of social media. The sharing of providers' personal experiences, involvement of patients' family in colonoscopy recommendations and propagation of patients' positive recounts were also more apparent in the past compared to the present decade, highlighting the need to reevaluate the balance between medical confidentiality and personal touch. Additionally, Asian patients were reportedly more apathetic towards CRC diagnosis due to their strong belief in destiny, a crucial association consistent with present studies. CONCLUSION This study highlights pertinent gaps in our healthcare system, providing crucial groundwork for interventions to be enacted in engendering higher colonoscopy uptake rates.
Published: 2020
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9. Afterthoughts on colonoscopy. Was it that bad?

Author: M K Devi, Choon S Chong, Cheng H Ng, Frances Lim, Glenn M Decruz, Chia H Tai, and Kia T Lim
Subjects: Oncology, medicine.medical_specialty, medicine.diagnostic_test, Colorectal cancer, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Colonoscopy, Cancer, medicine.disease, Colorectal cancer screening, Internal medicine, medicine, Humans, Colorectal Neoplasms, business, Early Detection of Cancer
Abstract: Objectives Colorectal cancer is among the top three most common cancers globally. In order to reduce the health burden, it is important to improve the uptake of colorectal cancer screening by understanding the barriers and facilitators encountered. There are numerous reports in the literature on the views of the general public on cancer screening. However, the experiences of colonoscopy patients are not as well studied. This paper maps their perceptions. Methods Keyword searches for terms such as ‘colorectal’, ‘colonoscopy’ and ‘qualitative’ were conducted on 3 December 2019 in five databases: Medline, Embase, CINAHL, PsycINFO and Web of Science Core Collection. Qualitative articles that quoted colonoscopy-experienced patients with no prior history of colorectal cancer were included for the thematic analysis. The systematic review was then synthesized according to PRISMA guidelines. Results The major themes were distilled into three categories: pre-procedure, during and post-procedure. The factors identified in the pre-procedure phase include the troublesome bowel preparation, poor quality of information provided and the dynamics within a support network. Perceptions of pain, emotional discomfort and the role of providers mark the experience during the procedure. The receipt of results, opportunities given for discussion and finances relating to colonoscopy are important post-procedure events. Conclusion Understanding colorectal cancer screening behaviour is fundamental for healthcare providers and authorities to develop system and personal level changes for the improvement of colorectal cancer screening services. The key areas include patient comfort, the use of clearer instructional aids and graphics, establishing good patient rapport, and the availability of individualized options for sedation and the procedure.
Published: 2020
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10. Effect of fall characteristics on the severity of hip impact during a fall on the ground from standing height

Author: Woochol Joseph Choi and K.-t. Lim
Subjects: musculoskeletal diseases, 0301 basic medicine, medicine.medical_specialty, Hip fracture, Standing height, Knee Joint, Hip Fractures, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, medicine.disease, Biomechanical Phenomena, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Orthopedic surgery, Humans, Medicine, Accidental Falls, 030101 anatomy & morphology, Impact, business, Bone Plates, Aged
Abstract: The magnitude of hip impact force during a fall on the ground (i.e., concrete surface) from standing height was determined. We found that this force decreases up to 59%, depending on how they land on the ground. We determined the magnitude of hip impact force that humans may experience in the event of a fall from standing height on the ground, in order to examine how the hip impact force was affected by characteristics of a fall. Twenty subjects mimicked a typical older adults’ falls on a mat. Trials were acquired with three initial fall directions: forward, sideways, and backward. Trials were also acquired with three knee positions at the time of hip impact: knee together, knee on the mat, and free knee. During falls, attenuated vertical hip impact forces and corresponding depression of the mat were measured via a force plate placed under the mat and motion capture system, respectively. Using a mass-spring model, actual hip impact force and body stiffness during a fall on the ground were estimated. Hip impact force averaged 4.0 kN (SD = 1.7). The hip impact force was associated with knee condition (F = 25.6, p
Published: 2020
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11. Click-cross-linked, doxorubicin-loaded hydrogels based on poly(styrene-alt-maleic anhydride)

Author: Cuong M.Q. Le, Kyu Hyun, G-D. Kim, Maheshkumar Prakash Patil, X. Li, Daru Seto Bagus Anugrah, K. T. Lim, and Kalyan Ramesh
Subjects: Materials science, Polymers and Plastics, General Chemical Engineering, injectable hydrogel, poly(styrene-alt-maleic anhydride), macromolecular substances, lcsh:Chemical technology, Styrene, tetrazine-norbornene click reaction, chemistry.chemical_compound, Polymer chemistry, Materials Chemistry, medicine, lcsh:TA401-492, Doxorubicin, lcsh:TP1-1185, Physical and Theoretical Chemistry, raft polymerization, Organic Chemistry, technology, industry, and agriculture, Maleic anhydride, chemistry, Self-healing hydrogels, polymer gels, lcsh:Materials of engineering and construction. Mechanics of materials, medicine.drug
Abstract: A new type of hydrogels based on poly(styrene-alt-maleic anhydride) (PSMA) was prepared via Diels-Alder click chemistry. The formulations consisting of tetrazine-functionalized PSMA as a multi-clickable polymer and norbornene-terminated poly(ethylene glycol) (PEG) as a polymeric cross-linker were used as precursors to give ultrafast hydrogels with controlled structures. The hydrogels formed within several minutes under a physiological condition without any catalyst, and their storage modulus (G′) values were in the range 0.3–1.7 kPa suitable for bio-applications. The pore structure and the release profile of doxorubicin hydrochloride (DOX・HCl) of the hydrogels could be manipulated by the molecular weight of PEG. The precursors exhibited practically no depressing effect of the normal HEK293 growth, while the DOX・HCl-loaded hydrogel presented significant anticancer activity towards HeLa cells. The results suggested this biocompatible hydrogel as a potential injectable drug depot for tumor sites.
Published: 2020

12. The COSMIC Bubble Helmet: A Non-Invasive Positive Pressure Ventilation System for COVID-19

Author: Vionarica Gusti, Wan Jun Wu, Arpan Grover, Sabian Chiu, Kai-Wen Su, Erica Ma, Chanelle K. Chow, Ella Sit, Jun Lim, Abhijit Pandhari, Mattias Park, Ryan Lee, Faisal Shahril, Shawn T. Lim, Christopher Y. Nguan, Dan Driedger, Avinash K. Sinha, Ivan G. Scrooby, Neilson J. Mclean, Michael W. Lee, Tyler D. Yan, and The COSMIC Team
Subjects: medicine.medical_specialty, ventilator, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, non-invasive, Computer applications to medicine. Medical informatics, R858-859.7, Seal (mechanical), Article, law.invention, pressure, law, Positive airway pressure, medicine, Medical technology, Continuous positive airway pressure, R855-855.5, Positive pressure ventilation, Intensive care medicine, COVID, Mechanical ventilation, business.industry, Non invasive, helmet, Ventilation (architecture), business
Abstract: Goal: COSMIC Medical, a Vancouver-based open-source volunteer initiative, has designed an accessible, affordable, and aerosol-confining non-invasive positive-pressure ventilator (NIPPV) device, known as the COSMIC Bubble Helmet (CBH). This device is intended for COVID-19 patients with mild-to-moderate acute respiratory distress syndrome. System Design : CBH is composed of thermoplastic polyurethane, which creates a flexible neck seal and transparent hood. This device can be connected to wall oxygen, NIPPVs including Continuous Positive Airway Pressure and Bi-level Positive Airway Pressure, and mechanical ventilators. Discussion : Justification of CBH design components relied on several factors, predominantly the safety and comfort of patients and healthcare providers. Conclusion: CBH has implications within and outside of the pandemic, as an alternative to invasive mechanical ventilation methods. We have experimentally verified that CBH is effective in minimizing aerosolization risks and performs at specified clinical requirements.
Published: 2020

13. Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures

Author: Hong Sheng Quah, Rachael Bashford-Rogers, Daniel S.W. Tan, Melvin L.K. Chua, Darren W. T. Lim, Annalisa Mupo, Lisda Suteja, Yvonne Hui-Fang Teng, George S. Vassiliou, N. Gopalakrishna Iyer, João Lopes Dias, Teng, Yvonne HF [0000-0002-4242-486X], Iyer, N Gopalakrishna [0000-0002-8812-6219], and Apollo - University of Cambridge Repository
Subjects: Research Report, Cancer Research, T cell, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, Human leukocyte antigen, Computational biology, Immune receptor, Biology, Public TCR, Virus, Antigen, Neoplasms, medicine, Tumor Microenvironment, Immunology and Allergy, Humans, Tumor microenvironment, T-cell receptor, Cancer, medicine.disease, Tumor-infiltrating T cells, TCR sharing, Immune repertoire sequencing, medicine.anatomical_structure, Oncology, T cell receptor
Abstract: Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-03047-7.
Published: 2021
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14. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Author: Gail E. Herman, Jennifer Reichert, Camilla Stoltenberg, Stephen Sanders, Menachem Fromer, Branko Aleksic, Julian Maller, Rachel Nguyen, Utku Norman, J. Jay Gargus, Donna M. Werling, David J. Cutler, Silvia De Rubeis, Kathryn Roeder, Ryan N. Doan, Sherif Gerges, Joseph D. Buxbaum, Per Magnus, Patrick Turley, Moyra Smith, Isaac N. Pessah, Rebecca J. Schmidt, Chiara Fallerini, Michael E. Talkowski, Carla Lintas, Pål Surén, Paige M. Siper, Duncan S. Palmer, Timothy W. Yu, Michael S. Breen, Sven Sandin, Esben Agerbo, Rich Belliveau, Antonio M. Persico, Elaine Cristina Zachi, Matthew W. State, Karoline Teufel, Margaret A. Pericak-Vance, Caitlin E. Carey, Ryan Collins, Lambertus Klei, Lara Tang, Mads V. Hollegaard, Ole Mors, Iuliana Ionita-Laza, Elisa Giorgio, Astanand Jugessur, Gerry Schellenberg, Christopher A. Walsh, A. Ercument Cicek, Caroline Dias, Gun Peggy Knudsen, Louise Gallagher, Elise B. Robinson, Abraham Reichenberg, Judith Miller, Ashley Dumont, Flora Tassone, Grace Schwartz, Peter Szatmari, Jacqueline I. Goldstein, Evelise Riberi, Brian H.Y. Chung, Stephen W. Scherer, Fátima Lopes, Jesslyn Jamison, Thomas Werge, Mara Parellada, Gabriela Soares, Hilary Coon, Shan Dong, Terho Lehtimäki, Norio Ozaki, Lauren A. Weiss, Susan L. Santangelo, F. Kyle Satterstrom, Daniel P. Howrigan, Emily Hansen-Kiss, Anders D. Børglum, Vivek Appadurai, Maria Rita Passos-Bueno, Hailiang Huang, Marcus C.Y. Chan, Eric M. Morrow, Stephen J. Guter, Catalina Betancur, Ditte Demontis, Matthew W. Mosconi, Pierandrea Muglia, Joanna Martin, Jack A. Kosmicki, Christine M. Freitag, Suma Jacob, W. Ian Lipkin, Angel Carracedo, Mark J. Daly, Andreas G. Chiocchetti, Eduarda Montenegro M. de Souza, Carsten Bøcker Pedersen, Isabela Maya Wahys Silva, Elizabeth E. Guerrero, Mafalda Barbosa, A. Jeremy Willsey, Maureen Mulhern, Claire Churchhouse, Raymond K. Walters, Timothy Poterba, Alessandra Renieri, Emilie M. Wigdor, Lauren M. Schmitt, Jennifer L. Moran, Mullin H.C. Yu, Edwin H. Cook, Jiebiao Wang, Behrang Mahjani, Kaitlin E. Samocha, Kaija Puura, Xin He, Ezra Susser, Aarno Palotie, Bernardo Dalla Bernardina, Montserrat Fernández-Prieto, Thomas Damm Als, Mykyta Artomov, Emma Wilkinson, Mads E. Hauberg, Enrico Domenici, Joon Yong An, Christine Søholm Hansen, Somer L. Bishop, Idan Menashe, So Lun Lee, Marianne Giørtz Pedersen, Alfredo Brusco, Nancy J. Minshew, Michael E. Zwick, Jesper Buchhave Poulsen, Elaine T. Lim, Benjamin M. Neale, Harrison Brand, Danielle Halpern, Elisabetta Trabetti, Alexander Kolevzon, Christine Stevens, Aurora Currò, Miia Kaartinen, Gal Meiri, Richard Anney, Søren Dalsgaard, Minshi Peng, Kimberly Chambert, Brooke Sheppard, Yunin Ludena, James S. Sutcliffe, Marie Bækvad-Hansen, Xinyi Xu, Audrey Thurm, Itaru Kushima, Michael Gill, Irva Hertz-Picciotto, Jonatan Pallesen, Stephan Ripke, Dara S. Manoach, Giovanni Battista Ferrero, Nell Maltman, Michael L. Cuccaro, David M. Hougaard, Javier González-Peñas, Wesley K. Thompson, Felecia Cerrato, Danielle de Paula Moreira, Jonas Bybjerg-Grauholm, Alicia R. Martin, Merete Nordentoft, John A. Sweeney, Alfonso Buil, Tarjinder Singh, Bernie Devlin, Jakob Grove, Daniel H. Geschwind, Manuel Mattheisen, Patrícia Maciel, Preben Bo Mortensen, Andrew J. Schork, Ryan Yuen, Christina M. Hultman, Maria del Pilar Trelles, Aparna Bhaduri, Sabine Schlitt, Diego Lopergolo, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Carnegie Mellon University [Pittsburgh] (CMU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of California [San Francisco] (UCSF), University of California, Korea University [Seoul], The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University [Aarhus], Center for Genomics and Personalized Medicine [Aarhus, Denmark] (CGPM), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research [San Francisco, CA, USA], Bilkent University [Ankara], University of California [Irvine] (UCI), Medical Investigation of Neurodevelopmental Disorders Institute [Davis, CA, USA] (MIND), University of California [Davis] (UC Davis), University of California-University of California, Boston Children's Hospital, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Illinois [Chicago] (UIC), University of Illinois System, Trinity College Dublin, Vanderbilt University School of Medicine [Nashville], National Institute of Mental Health (NIMH), Emory University School of Medicine, Emory University [Atlanta, GA], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Autism Sequencing Consortium : Branko Aleksic, Richard Anney, Mafalda Barbosa, Somer Bishop, Alfredo Brusco, Jonas Bybjerg-Grauholm, Angel Carracedo, Marcus C.Y. Chan, Andreas G. Chiocchetti, Brian H.Y. Chung, Hilary Coon, Michael L. Cuccaro, Aurora Curro´ , Bernardo Dalla Bernardina, Ryan Doan, Enrico Domenici, Shan Dong, Chiara Fallerini, Montserrat Ferna´ ndez-Prieto, Giovanni Battista Ferrero, Christine M. Freitag, Menachem Fromer, J. Jay Gargus, Daniel Geschwind, Elisa Giorgio, Javier Gonza´ lez-Pen˜ as, Stephen Guter, Danielle Halpern, Emily HansenKiss, Xin He, Gail E. Herman, Irva Hertz-Picciotto, David M. Hougaard, Christina M. Hultman, Iuliana Ionita-Laza, Suma Jacob, Jesslyn Jamison, Astanand Jugessur, Miia Kaartinen, Gun Peggy Knudsen, Alexander Kolevzon, Itaru Kushima, So Lun Lee, Terho Lehtima¨ ki, Elaine T. Lim, Carla Lintas, W. Ian Lipkin, Diego Lopergolo, Fa´ tima Lopes, Yunin Ludena, Patricia Maciel, Per Magnus, Behrang Mahjani, Nell Maltman, Dara S. Manoach, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Eduarda M.S. Montenegro, Danielle Moreira, Eric M. Morrow, Ole Mors, Preben Bo Mortensen, Matthew Mosconi, Pierandrea Muglia, Benjamin M. Neale, Merete Nordentoft, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio M. Persico, Isaac Pessah, Kaija Puura, Abraham Reichenberg, Alessandra Renieri, Evelise Riberi, Elise B. Robinson, Kaitlin E. Samocha, Sven Sandin, Susan L. Santangelo, Gerry Schellenberg, Stephen W. Scherer, Sabine Schlitt, Rebecca Schmidt, Lauren Schmitt, Isabela M.W. Silva, Tarjinder Singh, Paige M. Siper, Moyra Smith, Gabriela Soares, Camilla Stoltenberg, Pa˚ l Suren, Ezra Susser, John Sweeney, Peter Szatmari, Lara Tang, Flora Tassone, Karoline Teufel, Elisabetta Trabetti, Maria del Pilar Trelles, Christopher A. Walsh, Lauren A. Weiss, Thomas Werge, Donna M. Werling, Emilie M. Wigdor, Emma Wilkinson, A. Jeremy Willsey, Timothy W. Yu, Mullin H.C. Yu, Ryan Yuen, and Elaine Zachi. and iPSYCH-Broad Consortium : e Esben Agerbo, Thomas Damm Als, Vivek Appadurai, Marie Bækvad-Hansen, Rich Belliveau, Alfonso Buil, Caitlin E. Carey, Felecia Cerrato, Kimberly Chambert, Claire Churchhouse, Søren Dalsgaard, Ditte Demontis, Ashley Dumont, Jacqueline Goldstein, Christine S. Hansen, Mads Engel Hauberg, Mads V. Hollegaard, Daniel P. Howrigan, Hailiang Huang, Julian Maller, Alicia R. Martin, Joanna Martin, Manuel Mattheisen, Jennifer Moran, Jonatan Pallesen, Duncan S. Palmer, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Timothy Poterba, Jesper Buchhave Poulsen, Stephan Ripke, Andrew J. Schork, Wesley K. Thompson, Patrick Turley, and Raymond K. Walters., Norman, Utku, Çicek, A. Ercüment, Betancur, Catalina, University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki
Subjects: Male, INTELLECTUAL DISABILITY, genetic structures, MESH: Neurons, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Whole Exome Sequencing, Cohort Studies, 0302 clinical medicine, Gene Frequency, Neurobiology, MESH: Gene Expression Regulation, Developmental, Spectrum disorder, Exome, Developmental, genetics, Copy-number variation, excitatory-inhibitory balance, MESH: Cohort Studies, Exome sequencing, Genetics, Cerebral Cortex, Neurons, 0303 health sciences, MESH: Exome, autism spectrum disorder, cell type, cytoskeleton, excitatory neurons, exome sequencing, inhibitory neurons, liability, neurodevelopment, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Autism spectrum disorder, Female, Single-Cell Analysis, AGED 8 YEARS, MESH: Autistic Disorder, UNITED-STATES, GENETIC RISK, Biology, MESH: Phenotype, behavioral disciplines and activities, SAND DOMAIN, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, MESH: Whole Exome Sequencing, MESH: Neurobiology, mental disorders, medicine, MESH: Gene Frequency, Humans, Cell Lineage, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Autistic Disorder, Allele frequency, Case-Control Studies, Mutation, Missense, Gene Expression Regulation, Developmental, SPECTRUM DISORDER, COPY NUMBER VARIATION, 030304 developmental biology, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Cell Lineage, medicine.disease, MESH: Male, MESH: Cerebral Cortex, DISABILITIES MONITORING NETWORK, Gene Expression Regulation, DE-NOVO MUTATIONS, Mutation, Autism, Missense, MESH: Female, 030217 neurology & neurosurgery, MESH: Single-Cell Analysis
Abstract: International audience; We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
Published: 2020
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15. HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD–ligand interactions

Author: Parker D Webster, Douglas J. Tobias, Victoria T. Lim, Saleh Riahi, Jason D. Galpin, Francesco Tombola, Christopher A. Ahern, Liang Hong, and Chang Zhao
Subjects: 0301 basic medicine, Alanine, Mutation, Binding Sites, Arginine, Physiology, Mutagenesis, Endocytic cycle, Ligands, Ligand (biochemistry), medicine.disease_cause, Ion Channels, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, medicine, Biophysics, Humans, Protons, Binding site, Guanidine, 030217 neurology & neurosurgery
Abstract: The human voltage-gated proton channel Hv1 is a drug target for cancer, ischemic stroke, and neuroinflammation. It resides on the plasma membrane and endocytic compartments of a variety of cell types, where it mediates outward proton movement and regulates the activity of NOX enzymes. Its voltage-sensing domain (VSD) contains a gated and proton-selective conduction pathway, which can be blocked by aromatic guanidine derivatives such as 2-guanidinobenzimidazole (2GBI). Mutation of Hv1 residue F150 to alanine (F150A) was previously found to increase 2GBI apparent binding affinity more than two orders of magnitude. Here, we explore the contribution of aromatic interactions between the inhibitor and the channel in the presence and absence of the F150A mutation, using a combination of electrophysiological recordings, classic mutagenesis, and site-specific incorporation of fluorinated phenylalanines via nonsense suppression methodology. Our data suggest that the increase in apparent binding affinity is due to a rearrangement of the binding site allowed by the smaller residue at position 150. We used this information to design new arginine mimics with improved affinity for the nonrearranged binding site of the wild-type channel. The new compounds, named “Hv1 Inhibitor Flexibles” (HIFs), consist of two “prongs,” an aminoimidazole ring, and an aromatic group connected by extended flexible linkers. Some HIF compounds display inhibitory properties that are superior to those of 2GBI, thus providing a promising scaffold for further development of high-affinity Hv1 inhibitors.
Published: 2021
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16. Speech stimuli and nasalance scores for the assessment of resonance in in Mandarin speaking Malaysian children

Author: Hasherah Mohd Ibrahim, Chia T Lim, Hui W Lim, and Yazmin Ahmad Rusli
Subjects: Male, China, Linguistics and Language, medicine.medical_specialty, Nose, Audiology, Mandarin Chinese, 050105 experimental psychology, Language and Linguistics, Age and gender, 030507 speech-language pathology & audiology, 03 medical and health sciences, Speech and Hearing, Phonetics, otorhinolaryngologic diseases, medicine, Humans, Speech, 0501 psychology and cognitive sciences, Child, Language, 05 social sciences, Malaysia, language.human_language, language, Female, Nasalance, 0305 other medical science, Psychology
Abstract: This study was designed to develop language-specific stimuli for the assessment of resonance and to obtain nasalance scores using the newly developed speech stimuli in Mandarin. Gender and age influences on nasalance scores for each of the stimulus were also examined. Participants recruited were typically developing Mandarin-speaking ethnic Chinese children aged 6;00-7;11 growing up in Malaysia. Perceptual ratings of nasality were made based on the GOS.SP.ASS.'98 (revised) for children while nasalance scores were recorded for each stimulus using the Nasometer II (Model 6400). Fifty Mandarin-speaking children (24 males and 26 females) were recruited. None of the participants were perceived with abnormal nasality on the three stimuli. The mean nasalance scores for the Mandarin stimuli were 16.08% (SD = 2.57, 95% CI = 15.35-16.81) for the Oral passage, 25.20% (SD = 3.63, 95% CI = 24.17-26.23) for the Oral-Nasal passage and 55.44% (SD = 4.17, 95% CI = 54.25-56.63) for the Nasal passage. No significant age- and gender-related differences were observed for all the three stimuli. This is the first set of Mandarin stimuli and nasalance norms for Mandarin-speaking children in Malaysia. The influence of phonetic content on nasalance is supported. Findings call for language-specific normative nasalance data and careful selection of stimuli for the assessment of resonance.
Published: 2019
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17. Effect of Pulmonary Rehabilitation on Symptoms of Anxiety and Depression in COPD

Author: Steffan L. Cavalera, Carla S. Gordon, Rylee M. Cook, Christian R. Osadnik, Jacob W. Waller, and Wing T. Lim
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, Subgroup analysis, Critical Care and Intensive Care Medicine, Hospital Anxiety and Depression Scale, law.invention, 03 medical and health sciences, 0302 clinical medicine, Systematic review, 030228 respiratory system, Randomized controlled trial, law, Strictly standardized mean difference, Meta-analysis, Physical therapy, medicine, Anxiety, Pulmonary rehabilitation, 030212 general & internal medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background Pulmonary rehabilitation (PR) improves exercise capacity and quality of life in people with COPD; however, its effect on anxiety and depression symptoms is less clear. Existing data are difficult to apply to clinical PR because of diverse interventions and comparators. This review evaluated the effectiveness of PR on anxiety and depression symptoms in people with COPD. Methods A systematic review and meta-analysis (PROSPERO CRD42018094172) was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on randomized controlled trials comparing PR (≥ 4 weeks’ duration) with usual care. Four electronic databases were searched to February 2018 using terms related to COPD, PR, anxiety, and depression. Data were extracted by two assessors using standardized templates. Study quality was appraised via the PEDro scale, and evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation. Data were analyzed in RevMan 5.3, with pooled effect estimates reported as standardized mean differences (SMDs). The effect of the program duration (≤ 8 vs > 8 weeks) was explored via subgroup analysis. Results Eleven studies comprising 734 participants (median PEDro score, 4/10) were included. Compared with usual care, PR conferred significant benefits of a moderate magnitude for anxiety symptoms (SMD, −0.53; 95% CI, −0.82 to −0.23) and large magnitude for depression symptoms (SMD, −0.70; 95% CI, −0.87 to −0.53). The certainty of evidence for each outcome was moderate. Effects were not moderated by program duration. Conclusions PR confers significant, clinically relevant benefits on anxiety and depression symptoms. Because further studies involving no treatment control groups are not indicated, these robust estimates of treatment effects are likely to endure.
Published: 2019
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18. Measurement of electromyography during bobsleigh push-start: A comparison with world top-ranked athletes

Author: S.-T. Lim, S.-H. Park, and T.-W. Kim
Subjects: medicine.medical_specialty, medicine.diagnostic_test, biology, Athletes, business.industry, 030209 endocrinology & metabolism, 030229 sport sciences, Electromyography, biology.organism_classification, Biceps, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Orthopedics and Sports Medicine, Elite athletes, Muscle activity, business, Gastrocnemius medialis
Abstract: Summary Aims In the present study, we aimed to determine the muscles that mostly respond to the push-start of the sled. Methods Seven male Korea Winter Olympics elite athletes form the two-man bobsleigh team. Performance was assessed using push-start time. Electromyogram (EMG) activity of the rectus femoris (RF), tibialis anterior (TA), gastrocnemius medialis (GM), and biceps femoris (BF) muscles was recorded during the push-start phases. Results The paired t-test showed that right and left GM activity (P Conclusion This study provides preliminary evidence to suggest that BF muscle activity may represent an effective push-start time to reduce race time in bobsleigh athletes.
Published: 2019
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19. Comparison between general, spinal, epidural, and combined spinal-epidural anesthesia for cesarean delivery: a network meta-analysis

Author: S.-K. Park, M. Hur, Jae-Hyon Bahk, Won Ho Kim, Hyun Kyu Yoon, T. Lim, Seokha Yoo, and Jin-Tae Kim
Subjects: Anesthesia, Epidural, Network Meta-Analysis, Anesthesia, General, Anesthesia, Spinal, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Pregnancy, 030202 anesthesiology, law, Anesthesia, Obstetrical, Humans, Medicine, Cesarean delivery, Randomized Controlled Trials as Topic, Fetus, 030219 obstetrics & reproductive medicine, Cesarean Section, business.industry, Obstetrics and Gynecology, Odds ratio, Confidence interval, Anesthesiology and Pain Medicine, Anesthesia, Meta-analysis, Anesthetic, Apgar Score, Female, Apgar score, business, medicine.drug
Abstract: Background This study is a network meta-analysis to compare maternal and fetal outcomes associated with four different anesthetic techniques for cesarean delivery. Methods An arm-based, random-effects frequentist network meta-analysis was performed. A random effect model was selected considering deviance information criteria. Randomized trials reporting the following outcomes were included: Apgar score at 1- or 5-min; umbilical arterial and venous pH; umbilical arterial pH τ 2 . Quality of evidence was assessed using the GRADE approach. Results Data from 46 randomized trials including 3689 women contributed to the study. There were significant differences in Apgar score ≤6 at 1 min between spinal versus general anesthesia (odds ratio 0.27, 95% confidence interval [CI] 0.13 to 0.55: moderate quality evidence) and Apgar scores at 1- and 5-min, favoring spinal anesthesia. Umbilical venous pH associated with epidural anesthesia was significantly higher than that with general anesthesia (mean difference 0.010, 95% CI 0.001 to 0.020: moderate quality evidence) or spinal anesthesia. Spinal anesthesia was ranked best for Apgar score ≤6 at 1-min (SUCRA=89.8), Apgar score at 1-min (SUCRA=80.4) and 5-min (SUCRA=90.5). Epidural anesthesia was ranked highest for umbilical venous pH (SUCRA=87.4) and neonatal score (SUCRA=79.3). Conclusions Spinal and epidural anesthesia were ranked high regarding Apgar scores and epidural anesthesia was ranked high regarding umbilical venous pH, but the results were based on small heterogeneous studies with high or unclear risks of bias.
Published: 2019
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20. DIGITAL SPATIAL PROFILING OF DIFFUSE LARGE B‐CELL LYMPHOMAS REVEALS STING AS AN IMMUNE‐RELATED DETERMINANT OF SURVIVAL AFTER R‐CHOP THERAPY

Author: Anand D. Jeyasekharan, S. de Mel, S. T Lim, Choon Kiat Ong, Wee Joo Chng, A. VanSchoiack, Nicholas Francis Grigoropoulos, G Bertolazzi, Tiffany Tang, Michal Marek Hoppe, Li-Mei Poon, Shuangyi Fan, Joanne Shu Xian Lee, Patrick Jaynes, Y Peng, Y. L Chee, Claudio Tripodo, Xin Liu, Esther Hian Li Chan, and S.B. Ng
Subjects: Cancer Research, Sting, medicine.anatomical_structure, Immune system, Oncology, medicine, Cancer research, Hematology, General Medicine, Biology, B cell
Published: 2021
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21. MYC, BCL2 AND BCL6 COEXPRESSION PATTERNS AT SINGLE‐CELL RESOLUTION RE‐DEFINE DOUBLE EXPRESSOR LYMPHOMAS

Author: Susan Swee-Shan Hue, S. T Lim, Shih-Sung Chuang, Nicholas Francis Grigoropoulos, Y. L Chee, Anand D. Jeyasekharan, Phuong Mai Hoang, Hyungwon Choi, Anja Mottok, Xin Liu, Wee‐J Chng, Soo Yong Tan, Choon Kiat Ong, Shuangyi Fan, David W. Scott, Joseph D. Khoury, Tiffany Tang, Sheng-Tsung Chang, S. de Mel, Joanne Shu Xian Lee, Esther Hian Li Chan, Shaoying Li, S.B. Ng, Michal Marek Hoppe, Pedro Farinha, Claudio Tripodo, Patrick Jaynes, Y Peng, and Li-Mei Poon
Subjects: Physics, Cancer Research, medicine.anatomical_structure, Oncology, Cell, Resolution (electron density), medicine, Hematology, General Medicine, BCL6, Cell biology
Published: 2021
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22. CLINICAL APPLICATION OF AN EX‐VIVO PLATFORM TO GUIDE THE CHOICE OF DRUG COMBINATIONS IN RELAPSED/REFRACTORY LYMPHOMA; A PROSPECTIVE STUDY

Author: Yi Ching Yuen, Choon Kiat Ong, S. de Mel, L. K Tan, Masturah Bte Mohd Rashid, Nagavalli Somasundaram, Tiffany Tang, Xi Yun Zhang, Hoi‐Y Loi, Jasmine Goh, Y. L Chee, Anand D. Jeyasekharan, David S.P. Tan, Dachuan Huang, Joanne Shu Xian Lee, Xin Liu, Wee Joo Chng, Edward Kai-Hua Chow, S. T Lim, Daryl Ming Zhe Cheah, Jason Yongsheng Chan, Esther Hian Li Chan, Patrick Jaynes, S.B. Ng, Li-Mei Poon, Liang Piu Koh, Wan Lu Pang, X Goh, and T. G Soh
Subjects: Oncology, Drug, Cancer Research, medicine.medical_specialty, business.industry, media_common.quotation_subject, Hematology, General Medicine, medicine.disease, Lymphoma, Internal medicine, Relapsed refractory, medicine, Prospective cohort study, business, Ex vivo, media_common
Published: 2021
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23. Promoting Population Behavioral Health in a Safety-Net Health System During the COVID-19 Pandemic

Author: Philip S. Wang, Hsiang Huang, Nicholas Carson, Zev Schuman-Olivier, Colleen O'Brien, Lee A Robinson, Miriam C. Tepper, Carl E. Fulwiler, and Christopher T Lim
Subjects: education.field_of_study, Coronavirus disease 2019 (COVID-19), Population Health, business.industry, SARS-CoV-2, Safety net, Population, Psychological intervention, COVID-19, Population health, Government Programs, Psychiatry and Mental health, Environmental health, Pandemic, Health care, Medicine, Humans, Health risk, business, education, Pandemics
Abstract: The COVID-19 pandemic has been expected to lead to substantial increases in need for behavioral health care. A population health framework can facilitate the development of interventions and policies to promote the equitable distribution of care across the population. This column describes the application of population behavioral health principles in a safety-net health system during the pandemic. The approach includes stepped models of care, interventions to target individuals at high behavioral health risk, and measurement-based care. Early data suggest that these strategies have resulted in expanded behavioral health care capacity.
Published: 2021

24. A Literature Review of Rapid Prototyping and Patient Specific Implants for the Treatment of Orbital Fractures

Author: Christopher G. T. Lim, Danyon O. Graham, Jason Erasmus, and Peter Coghlan
Subjects: Rapid prototyping, medicine.medical_specialty, genetic structures, business.industry, Reviews, 030206 dentistry, Patient specific, eye diseases, 03 medical and health sciences, 0302 clinical medicine, Orbital trauma, Otorhinolaryngology, Orbital reconstruction, medicine, Surgery, Radiology, Oral Surgery, Orbit (control theory), 030223 otorhinolaryngology, Orbital Fracture, business, Intraoperative imaging
Abstract: Post-traumatic reconstruction of the orbit can pose a challenge due to inherent intraoperative problems. Intra-orbital adipose tissue is difficult to manipulate and retract making visualization of the posterior orbital contents difficult. Rapid prototyping (RP) is a cost-effective method of anatomical model production allowing the surgeon to produce a patient specific implant (PSI) which can be pre-surgically adapted to the orbital defect with exact reconstruction. Intraoperative imaging allows immediate assessment of reconstruction at the time of surgery. Utilization and combination of both technologies improves accuracy of reconstruction with orbital implants and reduces cost, surgical time, and the rate of revision surgery.
Published: 2021

25. Phase II, Randomized Study of Spartalizumab (PDR001), an Anti-PD-1 Antibody, versus Chemotherapy in Patients with Recurrent/Metastatic Nasopharyngeal Cancer

Author: Pei-Jen Lou, Roger K-C Ngan, Jennifer Marie Mataraza, Zujun Li, Hung-Ming Wang, Sebastian Szpakowski, Joël Guigay, Suebpong Tanasanvimon, Juan Gonzalez-Maffe, Chia Jui Yen, Steven L. McCune, Caroline Even, Luigi Manenti, Hongzi Liang, Somvilai Chakrabandhu, Brigette B.Y. Ma, V. Lee, Po Chung Chan, Arunee Dechaphunkul, Yao Yao, Li Zhang, Romain Sechaud, Alexander I. Spira, Darren W-T. Lim, Shau-Hsuan Li, and Ammar Sukari
Subjects: Cancer Research, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Phases of clinical research, Monoclonal antibody, Antibodies, Monoclonal, Humanized, Gastroenterology, law.invention, Randomized controlled trial, Drug Therapy, law, Internal medicine, Clinical endpoint, medicine, Humans, Adverse effect, Chemotherapy, biology, business.industry, Standard treatment, Nasopharyngeal Neoplasms, Oncology, biology.protein, Antibody, Neoplasm Recurrence, Local, business
Abstract: Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression. Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.
Published: 2021

26. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Eugenia Abaleke, Mustafa Abbas, Sadia Abbasi, Alfie Abbott, Ashraf Abdelaziz, Sherif Abdelbadiee, Mohamed Abdelfattah, Basir Abdul, Althaf Abdul Rasheed, Rezan Abdul-Kadir, Abdulfatahi Abdulmumeen, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer UA Abeer Ul Amna, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmad Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Devikumar Acharya, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Kate Adams, Richard Adams, Tim Adams, Malgorzata Adamus, Kirsty Adcock, Aderonke Adebiyi, Ken Adegoke, Vicki Adell, Aldrin Adeni, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Elizabeth Adeyeye, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Lynn Afari, Debbie Affleck, Carmel Afnan, Deborah Afolabi, Muhammad Afridi, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Judith Agwada-Akeru, Kwame A Agyapong, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Jonathan Ah-Chuen, Mahin Ahmad, Ashar Ahmed, Bilal Ahmed, Forizuddin Ahmed, Iram Ahmed, Irshad Ahmed, Liban Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Syed H Ahmed, Roa Ahmed Ali, Sana Ahmer, Dhiraj Ail, Adam Ainsley, Mark Ainsworth, Myriam Aissa, Lucy Aitchson, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Muhammad N Akhtar, Nasim Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Umeh Akudo, Asma Al Balushi, Majd Al Dakhola, Narendra Aladangady, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Lorraine Albon, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter DG Alexander, Julyan Al-Fori, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Anyat Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Katrin Alizaedeh, Maithem Al-Jibury, Moutaz Alkhusheh, Alison Allanson, Robert Allcock, Eireann Allen, Jonathan Allen, Kerry Allen, Louise Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Christine Almadenboyle, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Sakarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Amjad Amjad, Victoria Amosun, Khaled Amsha, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Prematie Andreou, Angela Andrews, Jill Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Bianca Araba, Angela Aramburo, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Dhawal Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Ganesh Arunachalam, Rita Arya, Salma Asam, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Ayesha Ashfaq, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Harshini Asogan, Julia Asplin, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Ahmed Attiq, Paula Aubrey, Suzannah August, Aye CT Aung, Hnin Aung, Kyaw Thu Aung, Nini Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Miriam Avery, Joanne Avis, Cristina Avram, Paula Avram, Gabriel Awadzi, Aszad Aya, Eman Ayaz, Amanda Ayers, Vivek Ayra, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Nasaruilla Babajan, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Adetona O Babs-Osibodu, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Kasra Bahadori, Gayathri Baijiu, Charles Bailey, Julie Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Peter Bailey, Hamish Baillie, Kenneth Baillie, Jennifer Bain, Karen Bain, Becky Bainton, David Baird, Yolanda Baird, Aiysha Bajandouh, Evelyn Baker, Johanne Baker, Kenneth Baker, Pearl Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Panos Bakoulas, Abhijit Bal, Niranjan Balachandran, Irvin Balagosa, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Cheryl Baldwick, Alexander Baldwin, Ashley Baldwin, Danielle Baldwin, Lisa Baldwin, Rebekah Baldwin-Jones, James Balfour, Ceri Ball, Craig Balmforth, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Kasun Bamunuarachchi, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Ritwik Banerjee, Sandip Banerjee, Harrison Banks, Luke Banks, Daniel Banner, Oliver Bannister, Christopher Bannon, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Desislava Baramova, Russell Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Charlotte Barclay, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Joseph B Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Amy Barnett, Debra Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Fiona Barrett, Jessica Barrett, Jazz Bartholomew, Sarah Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Ayten Basoglu, Amira Bassaly, G Bassett, Bengisu Bassoy, Anupam Basumatary, Adam Bataineh, Freddie Batalla, Tristan Bate, Harry John Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Rizvan Batha, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Miranda Baum, Carina Bautista, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Hannah Bayes, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Hannah Beadle, Wendy Beadles, Philip Beak, Andy Beale, Kathy Beardsal, Jack Bearpark, Karen Beaumont, Matthew Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Safia Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Lauren Bell, Louise Bell, Nicholas Bell, Stephanie Bell, Jennifer L Bell, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Ann Bennett, Caroline Bennett, Gillian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Vivienne Benson, Andrew Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Kimberley Best, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Helen Bexhell, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shweta Bhagat, Shiv Bhakta, Rekha Bhalla, Mahesh Bhalme, Khushpreet Bhandal, Kulbinder Bhandal, Ravina Bhanot, Prashanth Bhat, Nikhil Bhatia, Rahul Bhatnagar, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Alice Binns, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Mark Birt, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Sabrina Black, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Francesca Blakemore, Helen Blamey, Sujata Blane, Simon Blankley, Parry Blaxill, Jane Blazeby, Natalie Blencowe, Ben Bloom, Angela Bloss, Hannah Bloxham, Louise Blundell, Susara Blunden, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Bobruk, Pritesh Bodalia, Neena Bodasing, Gabriele Boehmer, Marta Boffito, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed Owais Bokhari, Ambrose Boles, Matthew Bolton, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Lizzy Bonney, Joanne Borbone, Stephanie Borg, Catherine Borra, Samuel Bosompem, Liam Botfield, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Karen Bourne, Michelle Bourne, Rachel Bousefield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Angie Bowring, Geetha Boyapati, Jenny Boyd, Laura Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Marie Branch, Emily Brandl-Salutz, Christina Branfield, Jamie Brannigan, Louise Brassington, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Morwenna Brend, Andrew Brereton, Chris Brewer, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Fiona Brogan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Alison Brooks, Kate Brooks, Nicole Brooks, Rachel Brooks, Sophie Brooks, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Charlotte Browne, Duncan Browne, Rachel Browne, Stephen Brownlee, David Bruce, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Luke Brunton, Margaret Brunton, Jade Bryant, Mark Bryce, Maya Buch, Ruaridh Buchanan, Amanda Buck, Elizabeth Buckingham, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, George Bugg, Ramadan Bujazia, Shanzay Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Sam Bullard, Naomi Bulteel, Katherine Bunclark, Roneleeh Bungue-Tuble, Caroline Burchett, Christy Burden, Thomas G Burden, Sarah Burge, Mika Burgess, Sophia Burgess, Emma Burke, Sara Burnard, Caroline Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Daniel Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Angus Butchart, Aaron Butler, Jo Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Ruth Cade, Donna Cairney, Claire Calderwood, James Calderwood, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee FD Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Laura Camrasa, Julie Camsooksai, Shaula M Candido, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Angelika Capp, Thomas Capstick, Simon Carley, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Patrick Carr, Sharon Carr, Anna Carrasco, Zoe Carrington, Jonathan Carter, Paul Carter, Penny Carter, Douglas Cartwright, Claire Carty, Jaime Carungcong, Paula Carvelli, Aisling Cashell, Barbara Cassimon, Teresa Castiello, Gail Castle, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Kerry Causer, Luke Cave, Frianne Cawa, Kathryn Cawley, Philippa Cawley, Chloe Caws, Hankins Cendl, Jeva Cernova, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, James Chalmers, Georgina Chamberlain, Sarah Chamberlain, Carol Chambers, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Shreekant Champanerkar, Carmen Chan, Cheuk Chan, Evelyn Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H Chan, Chris Chandler, Kim J Chandler, Zoe Chandler, Badrinathan Chandrasekaran, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Kevin Chatar, Calvin Chatha, Priyanka Chaturvedi, Muhammad YN Chaudhary, Iram Chaudhry, Zain Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Milan Chauhan, Ruchi S Chauhan, Nicola Chavasse, James Cheaveau, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Lok Y Cheng, Zhihang Cheng, Ashok Chengappa, Helen Chenoweth, Chun H Cheong, Shiney Cherian, Helen Cheshire, Sarah Chessell, Chee Kay Cheung, Elaine Cheung, Claire Cheyne, Swati Chhabra, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Amol Chingale, Heather Chisem, Ben Chisnall, Sunder Chita, Nihil Chitalia, Chipo Chitsenga, Matthew Chiu, Brenda Chivima, Soha Choi, Willy Choon Kon Yune, Khayzer Choudhary, Vandana Choudhary, Gary Chow, Muhibbur Chowdhury, Alexander Christides, Alex Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Izu Chukwulobelu, Favour Chukwunonyerem, Chi Y Chung, Jonathan Chung, Elaine Church, Sara R Church, David Churchill, Paola Cicconi, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Felicity Clark, Gabrielle Clark, James Clark, Katherine Clark, Lucy Clark, Matthew Clark, Patricia Clark, Richard Clark, Thomas Clark, Zoe Clark, Andrea Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Jayne Clemens, Carlota Clemente de la Torre, Suzanne Clements, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Peter GL Coakley, Kathryn Cobain, Susan Coburn, Alexandra Cochrane, Patricia Cochrane, Samantha Cockburn, Helen Cockerill, Shirley Cocks, Rhodri Codd, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Paul F Cofie, Danielle Cohen, Jonathan Cohen, Oliver Cohen, Mike Cohn, Louise Coke, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Nicholas Cole, Garry Coleman, Matt Coleman, Holly Coles, Julie Colley, Dawn Collier, Heather Collier, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Jennifer Collinson, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Dónal Concannon, Robin Condliffe, Lynne Connell, Natalie Connell, Gavin Connolly, Emma Connor, Antonia Conroy, Veronica Conteh, Rory Convery, Grainne Conway, Rhiannon Conway, Jo-Anna Conyngham, Eloise Cook, Gemma Cook, Helen Cook, Graham Cooke, Katrina Cooke, Catherine Coombs, Chris Cooper, Jamie Cooper, Joshua Cooper, Lauren Cooper, Rowena Cooper, Sophie Cooper, Thomas Cope, Carolyn Corbett, John Corcoran, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Pamela Corlett, Michael Cornwell, Diana Corogeanu, Ruth Corrigan, Rita Corser, Jon Cort, Denise Cosgrove, Patricia Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, James Coulson, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Elena Cowan, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Giles Cox, Karina Cox, Rebecca Cox, Karen Coy, Victoria Craig, Matthew Cramp, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Peter Creber, Joanne Cremona, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Jennifer Crooks, Harriet Crosby, Tim Cross, Stephen Crotty, Susan Crouch, Madeleine Crow, Rory Crowder, Becky Crowe, Rebecca Croysdill, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Gillian Cummings-Fosong, Victoria Cunliffe, Caroline Cunningham, Mishell Cunningham, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Gerens Curnow, Simon Curran, Scarlett Currie, Michelle Curtin, Jonathan Curtis, Katrina Curtis, Olivia Curtis, Rebecca Cuthbertson, Sean Cutler, Patrycja Czylok, Joana da Rocha, Sura Dabbagh, Helen Daggett, Jacqui Daglish, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Jolyon Dales, Helen Dalgleish, Dermot Dalton, Aoife Daly, Vaishnavi Dandavate, Akila Danga, Amelia Daniel, Priya Daniel, Allison Daniels, Sandra Danso-Bamfo, Alex Darbyshire, Janet Darbyshire, Paul Dark, Kate Darlington, Tom Darton, Guledew Darylile, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Mark Davey, Miriam Davey, Anette David, Mini David, Sarah David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Amanda Davies, Carolyn Davies, Catrin Davies, Drew Davies, Elaine Davies, Ffyon Davies, Helen Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa Davies, Matthew Davies, Michelle Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Wendy Davies, Gwyneth Davis, Illinos Davis, Peter Davis, Alexander Davison, Christine Dawe, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy Day, Parijat De, Henry de Berker, Duneesha de Fonseka, Toni de Freitas, Frederico de Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, James de Souza, Anthony de Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Jill Deane, James Dear, Effie Dearden, Catherine Deas, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Amanda Dell, Marilyn DeLuna, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Craig Denmade, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Susan Dermody, Amisha Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Prakash Dey, Vishal Dey, Rogin Deylami, Gurlove K Dhaliwal, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Sukhjit Dhariwal, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Kayleigh Diaz-Pratt, Pamela Dicks, Matthew Dickson, Sean Dillane, Sarah Diment, Paul Dimitri, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Nandita Divikar, Lavanya Diwakar, Masroor Diwan, Caroline Dixon, Catherine Dixon, Petr Dlouhy, Paul Dmitri, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, Morven Dockery, Emma Docks, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Denise Donaldson, Kate Donaldson, Sinead Donlon, Joanne Donnachie, Christopher Donnelly, Eilish Donnelly, Emma Dooks, Andrew Dooley, Kane Dorey, Sharon Dorgan, Davinder Dosanjh, Paula Dospinescu, Andrew Dougherty, Katie Douglas, Lucy Dowden, Michelle Dower, Sud Dowling, Hayley Downe, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Ronald Druyeh, Simon Drysdale, Hazel Dube, Judith Dube, Stephen Duberley, Simon Dubrey, Roger Duckitt, Hayley Duckles-Leech, Nicola Duff, Helen Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Janice Duignan, Simon Dummer, Andrew Duncan, Barrie Duncan, Christopher Duncan, Fullerton Duncan, Alessia Dunn, Damian Dunn, Laura Dunn, Karen Dunne, Fiona Dunning, Aidan Dunphy, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Alison Durie, Emily Durie, Laura Durrans, Hannah Durrington, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Harvey Dymond, Tom Dymond, Chris Eades, Melissa Earwaker, Nicholas Easom, Clare East, Jack Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Andrea Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Steven Edwards, Jenny Eedle, Dawn Egginton, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Kate El Bouzidi, Ashley Elden, Jennifer Elder, Haifa Eldew, Diana Eleanor, Maysoon Elfadil, Eman Elfar, Mayy M Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Amin Elkhawad, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Amy Elliott, Fiona Elliott, Kerry Elliott, Valmai Elliott, Annie Ellis, Hayley Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Rahma Elmahdi, Einas Elmahi, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Sarah Elyoussfi, Jonathan Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Charis Emmett, Michael Emms, Marieke Emonts, Angila Engden, Katy English, Nicola Entwistle, Hene Enyi, Ruth Erin Jones, Agota Ermenyi, Hanif Esmail, Ajmal Eusuf, Brynach Evans, Chris Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lynn Evans, Melanie Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Teriann Evans, Terry J Evans, Caroline Everden, Lynsey Evison, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Andy Fairclough, Louise Fairlie, Anne Fajardo, Euan Falconer, John Fallon, David Faluyi, Qayyum Farah, Novin Fard, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Frances Farnworth, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Alex Feben, Federico Fedel, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Lisa Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Sonia Fernandez Lopez, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Catarina Ferreira-De Almeida, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Joanne Finch, Laurie Finch, Natalie Fineman, Adam Finn, Joanne Finn, Sofia Fiouni, Jo Fiquet, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Marie Fisk, Jan Flaherty, Michael Flanagan, Charles Flanders, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Lucy Fletcher, Sophie Fletcher, Christopher Flood, Jonathan Flor, Vincent Florence, Sharon Floyd, Adama Fofana, Georgina Fogarty, Linda Folkes, Aiwyne Foo, Andrew Foot, Jayne Foot, Jane Forbes, Kathryn Forcer, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Victoria Francois, Sharon Frayling, Martyn Fredlund, Michael Freeborn, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Anastasia Fries, Matthew Frise, Renate Fromson, Claire Froneman, John Frost, Victoria Frost, Rachel Frowd, Arun Fryatt, Bridget Fuller, Elizabeth Fuller, Tracy Fuller, Duncan Fullerton, Sarah Funnell, John Furness, Hassina Furreed, Waqas Gaba, Elizabeth Gabbitas, Claire Gabriel, Joshua Gahir, Katarzyna Gajewska-Knapik, Christopher Gale, Hugo Gale, 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Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Nicola Griffiths, Oliver Griffiths, Sofia Grigoriadou, Steph Grigsby, Russell Gritton, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Sambasivarao Gurram, Ishy Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Samantha Hagan, Jack W Hague, Rosemary Hague, Andrew Haigh, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, 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Charlie H Harper, Heather Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Claire Harris, Jade Harris, Julie Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, David Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Tom Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Hans Hartung, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Neda Hasan, Brigitte Haselden, Mohammed Hashimm, Imranullah Hashmi, Zena Haslam, Abdulhakim Hassan, Adil Hassan, Ali Hassan, Waqar Ul Hassan, Philip Hassell, Alex Hastings, Bethany Hastings, Jonathan Hatton, Jennifer Haugh, May Havinden-Williams, Stefan Havlik, Dan Hawcutt, Liz Hawes, Nicola Hawes, Annie Hawkins, Nancy Hawkins, Daniel Hawley, Edward Haworth, Cathy Hay, Jamal Hayat, Anne Hayes, Melony Hayes, Fiona Hayes, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard 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Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Phoebe Hill, Annette Hilldrith, Catherine Hillman-Cooper, Zoe Hilton, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Jemma Hives, Benson Ho, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Simon Hodge, Lesley Hodgen, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Becky Holbrook, Catherine Holbrook, Catherine Holden, Jill Holden, Melinda Holden, Thomas Holder, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Marie Hollands, Elizabeth Holliday, Nina Holling, Nigel Hollister, Laszlo Hollos, Evelyn Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Lyndsey Holt, Siobhan Holt, Alexandra Holyome, Marie Home, Kate Hong, Andrew Hood, Clare Hooper, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Rachel Horn, Nicola Hornby, Sophie Horrocks, Latoya Horsford, Megan Horsford, Valana Horsham, Alex Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Ejaz Hossain, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Kathryn Houghton, Rebecca Houlihan, Gordon Houston, Hamish Houston, Eleanor Hoverd, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Richard Howard-Griffin, Serena Howe, Mark Howells, Lyn Howie, Alex Howlett, Sophie Howlett, Josh Hrycaiczuk, Desmond Hsu, Hein Htet, Zaw Htet, Naing Z Htoon, Su Htwe, Ying Hu, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Alison Hufton, Conor Huggins, Alistair Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rhian Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Charlotte Humphrey, Alasdair Humphries, Joanne Humphries, David Hunt, Fiona Hunt, Jane Hunt, Kristen Hunt, Luke Hunt, Karl Hunter, Neil Hunter, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Ibraar Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Rebecca Hussey, Christopher Hutchcroft, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Ahmed Ibrahim, Asil Ibrahim, Kamal Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Muhammad Idrees, Hina Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Haider Imtiaz, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Anil Ipe, Madiha Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Jane Ireland, Robert Irons, Mohannad Irshad, Muhammad S Irshad, Janice Irvine, Val Irvine, Robert Irving, Mina Ishak, Aminul Islam, Munim Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, M'hamedi Israa, Sharon Isralls, Shabana Issa, Monica Ivan, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Mia Iyer, Sriram Iyer, Alex Jackson, Amanda Jackson, Ben Jackson, Ella Jackson, Helen Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Patricia Jacob, Reni Jacob, Nicola Jacques, Anisa Jafar, Ali Jaffery, Vijay Jagannathan, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Yasmin Jameel, Albie James, Anneli James, Linda James, Mark James, Nicholas James, Olivia James, Ruth James, Tracy James, Jack Jameson, Eleana Jamieson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Lauren Jansen, 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Muhammad U Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Ali Khan, Al-Imran Khan, Asad Khan, Burhan Khan, Fatimah Khan, Kausik Khan, Lubna Khan, Malik A Khan, Marria Khan, Mohammad Khan, Mohammed R Khan, Nayeem Khan, Omar Khan, Rahila Khan, Shabana Khan, Shahul Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Sagira Khatun, Taslima Khatun, Chuen R Khaw, Htet HE Khin, Kiran Khokhar, Najaf Khota, Chloe Khurana, Shruti Khurana, Faith Kibutu, Andrew Kidd, Michelle Kidd, Joe Kidney, Shane Kidney, Will Kieffer, Caroline Kilby, Eliz Kilich, Jee Whang Kim, Sarah Kimber, Andy King, Barbara King, Jennifer King, Kirsten King, Rachel King, Sam King, Victoria King, Emily King-Oakley, Laura Kingsmore, Fiona Kinney, Jeremy Kirk, Amy Kirkby, Emily Kirkham, Gemma Kirkman, Ursula Kirwan, Toby Kitching, Laura Kitto, Lauren Kittridge, Sarah Klaczek, Susan Kmachia, Christopher Knapp, Lucy Knibbs, Alicia Knight, Fraser Knight, Marian Knight, Sarah Knight, Steven 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Nyan M Kyi, Laura Kyle, Stuart Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Robert Laing, Inez Laing-Faiers, Emily Laity, Nicki Lakeman, David Lalloo, Fiona Lalloo, Sarah-Jane Lam, Fiona Lamb, Thomas Lamb, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Michal Lamparski, Christine Lanaghan, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Matilda Lang, Stephen Lang, Daniel Langer, Maggie Langley, Charles Langoya, Emily Langthorne, Helen Langton, Scott Latham, John Latham-Mollart, Afzal Latheef, Nang Latt, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jessica Law, Penny Law, Richard Law, Emma Lawrence, Ryan Lawrie, Michael Lay, Stephen Laybourne, Christine Laycock, Reina Layug, Maria Lazo, Amelia Lea, William Lea, Ian Leadbitter, Samuel Leafe, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Todd Leckie, Marie Anne Ledingham, Emma Lee, Hannah 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MacDonald, Sheila MacFadyen, James G MacFarlane, Jill Macfarlane, Laura Macfarlane, Lisa MacInnes, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Colin MacLeod, Mary J MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Allan MacRaild, Alannah Madden, Mary Madden, Norman Madeja, Paula Madgwick, Madhavi Madhusudhana, Alpha Madu, Lorraine Madziva, Marion Mafham, Emma Magavern, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Natasha Mahabir, Subramanian Mahadevan-Bava, Anjanie Maharajh, Ajit Mahaveer, Bal Mahay, Hibo Mahdi, Thushika Mahendiran, Siva Mahendran, Sarah Maher, Shameera Maheswaran, Parisa Mahjoob-Afag, Ahmed Mahmood, Farhana Mahmood, Hager Mahmoud, Mian Mahmood, Waheed Mahmood, Ewan Mahony, Luke Mair, James Maitland, Rupert Major, Jaydip Majumdar, Mohammad KH Majumder, 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Martineau, Anthony Martinelli, Lauren Martinez, Jose Carlos Martinez Garrido, Vijay K Maruthamuthu, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Sanna Masih, Nick Maskell, Perry Maskell, Jon Maskill, Matthew Masoli, Richard Mason, Ruth Mason, Mohammad Masood, Mohammad T Masood, Syed Masood, Syed SME Masood, Lear Matapure, Cristina Matei, Manraj Matharu, Stephy Mathen, Nicole Mather, Jonathan Mathers, Joanna Matheson, Anna Mathew, Verghese Mathew, Jesha Mathews, Kate Mathias, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Szeto Matthew, Alison Jane Matthews, Edgar Maureen, Maria-Emanuela Maxan, Adam Maxwell, Veronica Maxwell, James May, Joanne May, Peter May, Philippa May, Matthew Maycock, Shelley Mayor, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, James McBurney, Amanda McCairn, Jake McCammon, Conor McCann, Alexandra McCarrick, Brendan 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Southworth, Jason Sowter, Claudia Spalding, Enti Spata, Katie Spears, Mark Spears, Branwell Spencer, Gisele Spencer, Sue Spencer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Johanna Sporrer, Oliver Spring, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Sybil Stacpoole, Louise Stadon, Jennifer Stahle, Nikki Staines, Roxana Stanciu, Grazyna Stanczuk, Simon Stapley, Natalie Staplin, Michelle Starr, Rachael Stead, Conor Steele, Paula Stefanowska, Alison Stephens, David Stephensen, Courtney Stephenson, Elaine Stephenson, Monique Sterrenburg, Will Stevens, Amy Stevenson, Andrew Stevenson, Daniel Stevenson, Lesley Stevenson, Sarah Stevenson, Claire Stewart, Grant Stewart, Richard Stewart, Jo Stickley, Beverley Stidolph, Gemma Stiller, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Lynne Stockham, Emma Stoddard, Chris Stokes, Ben Stone, Sarah Stone, Sophia Stone, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Emma Stratton, Jane Stratton, Sam Straw, Dieter Streit, Emma Stride, Sally Stringer, Sophia Strong-Sheldrake, Siske Struik, Carmel Stuart, Anna Stubbs, Harrison Stubbs, Ann Sturdy, Sharon Sturney, Matt Stuttard, Cristina Suarez, Karuna Subba, Chris Subbe, Manjula Subramanian, Vaidyanathan Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Taku Sugai, Peter Sugden, Rudresh Sukla, Ali Suliman, Fatimah Suliman, Sugrah Sultan, Alasdair Summers, Samyukta Sundar, Reka Sundhar, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Shilpa Suresh, Michael Surtees, Danielle Suter, Helen Sutherland, Rebecca Sutherland, Dovile Sutinyte, Deborah Sutton, Sam Sutton, Amy Sutton-Cole, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Thomas Swaine, Keshav Swarnkar, Tirion Swart, Ealish Swift, Pauline Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Yasir Syed, Catriona Sykes, Daisy Sykes, Dominic Symon, Lesley Symon, Jen Syson, Gemma Szabo, Tamas Szakmany, Megan Szekely, Matthew Szeto, Maria Tadros, Lucy Tague, Hasan Tahir, Abigail Takyi, James Talbot-Ponsonby, Bradley Tallon, Bee TT Tan, Hock Tan, Huey Tan, WeiTeen Tan, Anand Tana, Rebecca Tangney, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Hayley Tarft, Syed Tariq, David Tarpey, Antonia Tasiou, Elizabeth Tatam, Margaret Louise Tate, Paul Tate, Kate Tatham, Vera Tavoukjian, Alexander Taylor, Andrew Taylor, Beverley Taylor, Claire Taylor, David Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tracey Taylor, Vicky Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Jessica Teasdale, Julie Tebbutt, Caroline Tee, Adam Telfer, Vibha Teli, Jennifer Tempany, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Lynne Terrett, Louise Terry, Dariusz Tetla, Daniel Tewkesbury, Manish Thakker, Mini Thankachen, Dushen Tharmaratnam, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Byron Theron, Phyu Thet, Kapeendran Thevarajah, Brinda Thillainathan, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Amy Thomas, Andrew Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Helen Thomas, James Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Megan Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Rhian Thomas-Turner, Catherine Thompson, Christopher Thompson, Clara Thompson, Fiona Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Orla Thompson, Roger Thompson, Jason Thomson, Nicola Thomson, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Jim Thornton, Richard Thornton, Sarah Thornton, Susan Thornton, Thomas Thornton, Christopher Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Guy Thwaites, Simon Tiberi, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Amanda Tiller, Elizabeth Timlick, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Sophie Tisi, Helen Tivenan, Suzy Tluk, Helen T-Michael, Anne Todd, Jackie Todd, Stacy Todd, Mohamed Tohfa, Melanie Tolson, Ana L Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Ivan Tonna, Kirsty Topham, Mathew Topping, Parisa Torabi, M Estee Torok, Mark Toshner, Ruhaif Tousis, Peter Tovey, Gareth Towersey, Jill Townley, Richard Tozer, Myat T Trafford, Helen Tranter, Christopher Travill, Sarah Traynor, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Alex Trimmings, Tom Trinick, Maria Tripouki, Ashifa Trivedi, Dawn Trodd, Amy Trotter, Madeleine Trowsdale Stannard, Nigel Trudgill, Daniel Trushell-Pottinger, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Simon Tso, Sally Tucker, Aisha Tufail, Redmond Tully, Killian Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Kate Turner, Kelly Turner, Lucy Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Victoria Turner, Sharon Turney, Jon Turvey, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Mohammad S Uddin, Ruhama Uddin, Salamat Ullah, Sanda Ullah, Athavan Umaipalan, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Lizzie Undrell, Adam Unsworth, Veerpal SU Uppal, Gerry Upson, Alison Uriel, Sebastian Urruela, Hiromi Uru, Miranda Usher, Rebecca Usher, Andrew Ustianowski, Linda C Vaccari, Abhay Vaidya, Erika Vainieri, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne Van Koutrik, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Anu Varghese, Maria Varghese, Teena Varghese, William Varney, Giulia Varnier, Valeria Vasadi, Vimal Vasu, Vasanthi Vasudevan, Ramu Vathenen, Manu Vatish, Heloyes Vayalaman, Christopher Vaz, Niki Veale, Bar Velan, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Lyn Ventilacion, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Britney Vernon, Nathan Vernon, Mark Vertue, Natalie Vethanayagam, Lucy Veys, Jennifer Vidler, Denise Vigni, Vinod W Vijayaraghavan Nalini, Enric Vilar, Neringa Vilimiene, Joseph Villiers, Sylvia Vinay, Latha Vinayakarao, Rachel Vincent, Rosie Vincent, Lisa Vincent Smith, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Karunakaran Vithian, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Kirsten Wadsworth, Syed EI Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Khalilullah Wahdati, Sawan Waidyanatha, Rachel Wake, Alice Wakefield, Emma Wakefield, Harry Wakefield, William Wakeford, Fiona Wakinshaw, Andrew Walden, Lorna Walding, Claire Walker, Ian Walker, Kevin Walker, Kim Walker, Linda Walker, Marie Walker, Rachel Walker, Susan Walker, Elaine Wall, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Michael Waller, Rosemary Waller, Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Lani Walshaw, Daniel Walter, Holt Walters, Jocelyn Walters, Eileen Walton, Maggie Walton, Michael Walton, Olivia Walton, Susan Walton, Mandy Wan, Thin Wan, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Katie Ward, Luke Ward, Rachael Ward, Thomas Ward, Scott A Warden, Steve Wardle, Hassan Wardy, Tobias Wareham, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Adam JR Watson, Ekaterina Watson, Eleanor Watson, Paul Watson, Robert Watson, Malcolm Watters, Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Nick Weatherly, Hayley Webb, Kathryn Webb, Stephen Webb, Ian Webster, Tim Webster, Ling Wee, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Freshtah Weidi, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Samantha Weller, Claire Wells, Susan Wellstead, Berni Welsh, RIchard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, Magdelena West, Raha West, Ruth West, Sophie West, Heather Weston, Alice Westwood, Bill Wetherall, Helen Wheeler, Matthew Whelband, Amanda Whileman, Jenny Whitbread, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Sophie Whiteley, Gabriel Whitlingum, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Eunice Wiafe, Lou Wiblin, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Karen Wild, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Felicity Williams, Gail Williams, Hannah Williams, James Williams, Jennie Williams, John Williams, Joseph JR Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Debbie Wilson, James Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Toni Wilson, Tim Wilson, Marlar Win, Tin T Win, Lucinda Winckworth, Laura Winder, Piers Winder, Nicola Window, Simon Winn, Carmen Winpenny, Helen Winslow, Martin Winstanley, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Stephen Wisdom, Martin Wiselka, Sophie Wiseman, Steven Wishart, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Chi-Hung Wong, Edwin Wong, Jessica SY Wong, Kit Y Wong, Nick Wong, Sam Wong, Caroline Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Michelle Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Jane Woods, Katherine Woods, Sarah Woods, Elizabeth Woodward, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Stephy Worton, Jonathan Wraight, Lynn Wren, Caroline Wrey Brown, Demi Wright, Francesca Wright, Imogen Wright, Lianne Wright, Rachel Wright, Caroline Wroe, Henry Wu, Peishan Wu, Pensee Wu, Johnathan Wubetu, Retno Wulandari, Kim Wyness, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Zhongyang Xia, Masseh Yakubi, May Yan, Michael Yanney, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Robert Yellon, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche Melly, Inez Ynter, Cissy Yong, Jemma Yorke, Abdel Younes Ibrahim, Gail Young, Louise Young, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Ausra Zdanaviciene, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Jane Zhixin, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei T Zin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Carol Zullo, Ana Zuriaga-Alvaro, National Institute for Health Research, UK Research and Innovation, University of St Andrews. School of Medicine, Horby, PW, Roddick, A, Spata, E, Staplin, N, Emberson, JR, Pessoa-Amorim, G, Peto, L, Day, J, Thwaites, G, Mafham, M, Haynes, R, and Landray, MJ
Subjects: Male, medicine.medical_treatment, 030204 cardiovascular system & hematology, Azithromycin, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Rate ratio, chemistry.chemical_compound, 0302 clinical medicine, RA0421, Oxygen therapy, RA0421 Public health. Hygiene. Preventive Medicine, 030212 general & internal medicine, Hospital Mortality, 11 Medical and Health Sciences, azithromycin, education.field_of_study, Covid19, clinical trial, General Medicine, 3rd-DAS, Middle Aged, Hospitalization, Survival Rate, Treatment Outcome, Humanitarian and Conflict Response Institute, Female, Life Sciences & Biomedicine, medicine.medical_specialty, RM, Population, COVID-19/drug therapy, Azithromycin/therapeutic use, 03 medical and health sciences, Pharmacotherapy, Tocilizumab, Medicine, General & Internal, SDG 3 - Good Health and Well-being, Internal medicine, General & Internal Medicine, medicine, Humans, education, Survival rate, Mechanical ventilation, Science & Technology, business.industry, COVID-19, NIS, Length of Stay, R1, United Kingdom, COVID-19 Drug Treatment, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, chemistry, Relative risk, business, RA, Anaesthesia Pain and Critical Care
Abstract: The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation (Medical Research Council) and NIHR (MC_PC_19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_0002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24). Interpretation: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Publisher PDF
Published: 2021
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27. NeissLock provides an inducible protein anhydride for covalent targeting of endogenous proteins

Author: Shabaz Mohammed, Felix J. Metzner, Mark Howarth, Sheryl Y. T. Lim, and Arne H. A. Scheu
Subjects: 0301 basic medicine, Proteolysis, Recombinant Fusion Proteins, Science, Chemical biology, General Physics and Astronomy, 010402 general chemistry, Protein Engineering, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Article, Anhydrides, 03 medical and health sciences, Bacterial Proteins, medicine, Animals, Ornithine decarboxylase antizyme, Multidisciplinary, medicine.diagnostic_test, Staining and Labeling, Chemistry, Binding protein, Membrane Proteins, General Chemistry, computer.file_format, Protein engineering, Protein Data Bank, 0104 chemical sciences, Molecular Imaging, 030104 developmental biology, Biochemistry, Covalent bond, Molecular Probes, Target protein, Protein design, Structural biology, computer, Chemical modification
Abstract: The Neisseria meningitidis protein FrpC contains a self-processing module (SPM) undergoing autoproteolysis via an aspartic anhydride. Herein, we establish NeissLock, using a binding protein genetically fused to SPM. Upon calcium triggering of SPM, the anhydride at the C-terminus of the binding protein allows nucleophilic attack by its target protein, ligating the complex. We establish a computational tool to search the Protein Data Bank, assessing proximity of amines to C-termini. We optimize NeissLock using the Ornithine Decarboxylase/Antizyme complex. Various sites on the target (α-amine or ε-amines) react with the anhydride, but reaction is blocked if the partner does not dock. Ligation is efficient at pH 7.0, with half-time less than 2 min. We arm Transforming Growth Factor-α with SPM, enabling specific covalent coupling to Epidermal Growth Factor Receptor at the cell-surface. NeissLock harnesses distinctive protein chemistry for high-yield covalent targeting of endogenous proteins, advancing the possibilities for molecular engineering., Covalent conjugation of endogenous protein complexes offers many opportunities for fundamental and clinical research. Based on a bacterial protein domain that forms a reactive anhydride in the presence of Ca2+, the authors here develop a system that enables the covalent capture of endogenous binding partners.
Published: 2021
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28. Caecal volvulus or acute cholecystitis?

Author: Sean Ng Kwet Chi Ng Ying Kin, Michelle Zhiyun Chen, James T. Lim, Yeng Kwang Tay, Yeu Sheng Ang, Mikhail Fisher, and Asiri Arachchi
Subjects: medicine.medical_specialty, business.industry, Cholecystitis, Acute, General Medicine, Gastroenterology, Internal medicine, Acute cholecystitis, Cecal Diseases, Humans, Medicine, Surgery, business, Caecal volvulus, Intestinal Obstruction, Intestinal Volvulus
Published: 2021
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29. Data integration of bulk and single-cell transcriptomics from cerebral organoids and post-mortem brains to identify cell types and cell type specific driver genes in autism

Author: Julia M. Reichert, Bruce A. Yankner, Elaine T. Lim, Katharina Meyer, Mannix J. Burns, Serkan Erdin, Ying Kai Chan, Derek J. C. Tai, Joel N. Hirschhorn, Yingleong Chan, Xiaoge Guo, James F. Gusella, Christopher T. Walsh, Michael E. Talkowski, Soumya Raychaudhuri, Xiaochang Zhang, Jessica J. Chiang, and George M. Church
Subjects: Cell type, Single cell transcriptomics, Cell type specific, Organoid, medicine, Autism, Biology, medicine.disease, Gene, Cell biology
Abstract: Human-derived cerebral organoids demonstrate great promise for identifying cell types and cell type specific molecular processes perturbed by genetic variants associated with neuropsychiatric and neurodevelopmental disorders, which are notoriously challenging to study using animal models. However, considerable challenges remain in achieving robust, scalable and generalizable phenotyping of organoids to discover cell types and cell type specific genes. We perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data from human post-mortem brains and cerebral organoids, for the identification of cell types and cell type specific individual genes. We apply Orgo-Seq for two autism-associated loci: 16p11.2 deletions and 15q11-13 duplications, and identify neuroepithelial cells as critical cell types for 16p11.2 deletions, and discover novel and previously reported cell type specific driver genes. Finally, we validated our results that mutations in the KCTD13 gene in the 16p11.2 locus lead to imbalances in the proportion of neuroepithelial cells, using CRISPR/Cas9-edited mosaic organoids. Our work presents a quantitative technological framework to integrate multiple transcriptomics datasets to identify cell types and cell type specific driver genes associated with complex diseases using cerebral organoids.
Published: 2020
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30. Identifying cell type specific driver genes in autism-associated copy number loci from cerebral organoids

Author: George M. Church, Derek J. C. Tai, Soumya Raychaudhuri, Katharina Meyers, Xiaoge Guo, Bruce A. Yankner, Michael E. Talkowski, Elaine T. Lim, James F. Gusella, Christopher A. Walsh, Yingleong Chan, Mannix J. Burns, Julia M. Reichert, Joel N. Hirschhorn, Ying Kai Chan, Xiaochang Zhang, Jessica J. Chiang, and Serkan Erdin
Subjects: Neuroepithelial cell, Cell type, medicine, Organoid, Autism, CRISPR, RNA, Locus (genetics), Computational biology, Biology, medicine.disease, Gene
Abstract: Neuropsychiatric and neurodevelopmental disorders have been particularly challenging to study using animal models, and recently, human-derived cerebral organoids demonstrate great promise for discovering molecular processes that are important in these disorders. However, several challenges remain in achieving robust phenotyping to discover cell type specific genes. We perform RNA sequencing on 71 samples comprising of 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to identify cell type specific driver genes, for 16p11.2 deletions and 15q11-13 duplications. We identify neuroepithelial cells as critical cell types for 16p11.2 deletions, and discover novel and previously reported cell type specific driver genes. Finally, we validated our results that mutations in KCTD13 in the 16p11.2 locus lead to imbalances in the proportion of neuroepithelial cells, using CRISPR/Cas9-edited mosaic organoids. Our work presents a quantitative discovery and validation framework for identifying cell type specific driver genes associated with complex diseases using cerebral organoids.
Published: 2020
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31. A Case of Catatonia in a Man with COVID-19

Author: Marissa P. Caan, Mark Howard, and Christopher T Lim
Subjects: medicine.medical_specialty, Infection risk, Coronavirus disease 2019 (COVID-19), Catatonia, Article, Psychiatric history, Arts and Humanities (miscellaneous), Altered Mental Status, medicine, Intensive care medicine, Applied Psychology, business.industry, SARS-CoV-2, COVID-19, Lorazepam, medicine.disease, Neuropsychiatry, Consultation Liaison Psychiatry, Coronavirus, Psychiatry and Mental health, Etiology, Respiratory Disorder, Substance use, business, medicine.drug
Abstract: Introduction Catatonia has been associated with many medical conditions, including systemic infections. Several neuropsychiatric sequelae of coronavirus disease 2019 (COVID-19) have been identified to date. Case We describe a case of catatonia in a patient with COVID-19. He had no prior medical, substance use, or psychiatric history. His condition improved with administration of lorazepam. Discussion Potential etiologies of this patient’s catatonia are explored, including COVID-19 itself, medications, and an acute presentation of a psychiatric disorder. The limitations posed by infection risk on psychiatric evaluations are discussed. Conclusion We highlight the importance of considering catatonia in the diagnosis of altered mental status. We also identify catatonia as a potential neuropsychiatric consequence of COVID-19
Published: 2020

32. SUN-424 Treatment of Antithyroid Drug-Induced Agranulocytosis with Granulocyte Colony-Stimulating Factor: A Meta-Analysis

Author: Alma R Calavera, Maria Regina C Santos, Ramon Jason M Javier, and Christian Emmanuel T Lim
Subjects: Thyroid, business.industry, Endocrinology, Diabetes and Metabolism, Meta-analysis, Medicine, Pharmacology, Benign Thyroid Disease and Health Disparities in Thyroid II, business, AcademicSubjects/MED00250, Drug-induced agranulocytosis, Granulocyte colony-stimulating factor
Abstract: BACKGROUND: Hyperthyroidism, a common condition seen by physicians, is predominantly treated with antithyroid drugs. Agranulocytosis, a potentially fatal complication, is their most serious side effect. Conflicting studies are present between the risks and benefits of the use of exogenous granulocyte colony-stimulating factor (G-CSF) in its treatment, since its pathogenesis has not been established. The objective of this study is to determine the benefit of G-CSF in antithyroid drug-induced (ATD) agranulocytosis, through a meta-analysis. Methods: Studies were included after extensive literature search in five electronic databases; all met the inclusion and exclusion criteria, and were critically appraised. The primary outcome was days to hematologic recovery, defined as neutrophilic rise to >0.5 x 109/L. Data were treated as continuous data, obtaining the standard mean difference through a Forrest Plot using the Review Manager 5.3 application. Results: Five of the studies were non-concurrent cohort, while one was a randomized clinical trial. The duration of the studies was from 1970s to 2014. Age range of the population was from 8 to 87 years old, with more females. G-CSF dose ranged from 75 to 300ug/day, injected subcutaneously or intramuscularly. Primary outcome measured common to all the studies included hematologic recovery. Five of the six studies showed shorter number of days to hematologic recovery for the treatment group compared to the control group (with a standardized mean difference of 1 day, confidence interval (CI) of 0.45 to 1.54). Conclusion: Exogenous G-CSF administration in ATD agranulocytosis contributed to faster hematologic recovery in terms of days, shortening recovery by a mean of 1 day. References: 1. Tamai, H., et al. Treatment of methimazole-induced agranulocytosis using recombinant human granulocyte colony-stimulating factor (rhG-CSF). J Clin Endocrinol Metab. 1993;77(5):1356-1360. 2. Andres, E., et al. Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis. Q J Med. 2001;94:423-428. 3. Fukata, S., Kuma, K., Sugawara, M. Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study. Thyroid. 1999;9(1):29-31. 4. Tajiri, J., Noguchi, S. Antithyroid drug-induced agranulocytosis: how has granulocyte colony-stimulating factor changed therapy? Thyroid. 2005;15(3):292-297. 5. Watanabe, N., et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves’ disease. J Clin Endocrinol Metab. 2012;97(1):E49-E53. 6. Clauna-Lumanta, M.M., Yao, C., Bolinao, J.F. The effects of GCSF on the recovery time and duration of hospitalization in patients with anti-thyroid drug-induced agranulocytosis in a tertiary hospital. JAFES. 2016;31(2):131-136.
Published: 2020
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33. PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis

Author: Neha Singh, James T. Lim, Richard B. Lock, David T. Teachey, Valerie S. Calvert, Sathish K.R. Padi, Emanuel F. Petricoin, Megha Padi, Libia A. Leuvano, and Andrew S. Kraft
Subjects: 0301 basic medicine, Cancer Research, T cell, PIM1, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Article, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Mice, 0302 clinical medicine, Proto-Oncogene Proteins c-pim-1, Cell Line, Tumor, medicine, Animals, Humans, Gene Regulatory Networks, Protein kinase A, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, Homeodomain Proteins, Chemistry, Kinase, Sequence Analysis, RNA, Gene Expression Profiling, TOR Serine-Threonine Kinases, NF-kappa B, medicine.disease, Xenograft Model Antitumor Assays, Up-Regulation, Gene Expression Regulation, Neoplastic, Leukemia, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cell culture, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, Phosphorylation, Signal Transduction
Abstract: Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small-molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, treatment of animals carrying ETP-ALL with PIMi was not curative. To model other pathways that could be targeted to complement PIMi activity, HSB-2 cells, previously characterized as a PIMi-sensitive T-ALL cell line, were grown in increasing doses of PIMi. Gene set enrichment analysis of RNA sequencing data and functional enrichment of network modules demonstrated that the HOXA9, mTOR, MYC, NFκB, and PI3K-AKT pathways were activated in HSB-2 cells after long-term PIM inhibition. Reverse phase protein array–based pathway activation mapping demonstrated alterations in the mTOR, PI3K-AKT, and NFκB pathways, as well. PIMi-tolerant HSB-2 cells contained phosphorylated RelA-S536 consistent with activation of the NFκB pathway. The combination of NFκB and PIMis markedly reduced the proliferation in PIMi-resistant leukemic cells showing that this pathway plays an important role in driving the growth of T-ALL. Together these results demonstrate key pathways that are activated when HSB-2 cell line develop resistance to PIMi and suggest pathways that can be rationally targeted in combination with PIM kinases to inhibit T-ALL growth.
Published: 2020

34. Effects of meaningful weight loss beyond symptomatic relief in adults with knee osteoarthritis and obesity: a systematic review and meta-analysis

Author: A. Y. T. Lim, I. J. H. Chu, and C. L. W. Ng
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Public Health, Environmental and Occupational Health, Osteoarthritis, medicine.disease, Symptomatic relief, Obesity, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Weight loss, Meta-analysis, Physical therapy, Medicine, 030212 general & internal medicine, medicine.symptom, business, Body mass index
Abstract: Existing clinical guidelines recommend weight loss for adults with knee osteoarthritis and obesity, but the supporting evidence to date remains inadequate. There is also no pooled data on physical function and quality of life. This study aims to examine the efficacy of weight loss on pain, self-reported disability, physical function and quality of life in adults with knee osteoarthritis and obesity. A systematic database search (from 1990 to June 2017) was conducted, and seven studies were eligible for inclusion. The meta-analyses demonstrated that a 5% to 10% weight loss significantly improved pain (effect size 0.33, 95% confidence intervals 0.17 to 0.48), self-reported disability (effect size 0.42, 95% confidence intervals 0.25 to 0.59) and quality of life (physical) (effect size 0.39, 95% confidence intervals 0.24 to 0.54). The results were based on adults with mean body mass index 33.6 to 36.4 kg m-2 and mild to moderate knee osteoarthritis. Results for physical function were inconclusive due to the lack of eligible studies and incomprehensive outcome measures used.
Published: 2018
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35. Challenges of managing a first episode of pediatric catatonia

Author: Jessica L. Stern and Christopher T. Lim
Subjects: Male, First episode, medicine.medical_specialty, Adolescent, business.industry, Catatonia, Developmental Disabilities, medicine.disease, Benzodiazepines, Psychiatry and Mental health, Humans, Medicine, business, Psychiatry, Biological Psychiatry
Published: 2019
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36. P76.88 Real-World Data of Osimertinib in Patients with Metastatic EGFRm+ NSCLC who Progressed on First-Line EGFR TKIs

Author: Amit Jain, Wan Ling Tan, Sze Huey Tan, Ravindran Kanesvaran, T. Rajasekaran, Quan Sing Ng, Mei-Kim Ang, J. Ma, A. Tran, Angela Takano, Kiat Hon Lim, Daniel Shao Weng Tan, D.W.-T. Lim, D. Yin, and Eng Huat Tan
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Egfr tki, business.industry, First line, Internal medicine, medicine, In patient, Osimertinib, business, Real world data
Published: 2021
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37. OA06.05 Molecular and Clinical Features Associated with Relapse in Early Stage EGFR-Mutated NSCLC: A Single Institution Knowledge Bank

Author: Wan Ling Tan, D.W.-T. Lim, Mei-Kim Ang, Amit Jain, S. Zhou, T. Rajasekaran, J. Chen, Daniel Shao Weng Tan, Anders Jacobsen Skanderup, Kam Weng Fong, Angela Takano, Kevin L.M. Chua, Eng Huat Tan, Kiat Hon Lim, T. Koh, G. Lai, S.P.L. Saw, B.H. Ong, Ravindran Kanesvaran, Xin Min Cheng, and Quan Sing Ng
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, business.industry, Internal medicine, medicine, Stage (cooking), Single institution, business
Published: 2021
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38. Moving beyond the initial colonoscopy: a call for action

Author: Kamala M. Devi, Choon S Chong, Kia T Lim, Sneha Rajiv Jain, Yip Han Chin, Glenn M Decruz, and Cheng H Ng
Subjects: Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, Epidemiology, business.industry, Colorectal cancer, Public Health, Environmental and Occupational Health, MEDLINE, Colonoscopy, PsycINFO, Patient counseling, CINAHL, medicine.disease, Oncology, Action (philosophy), Family medicine, Health care, medicine, business
Abstract: Introduction The evolution of colorectal screening has made headway with continual efforts globally to increase screening rates for colonoscopy-naive patients. However, little has been done to encourage repeat colonoscopies after the initial scope despite recommendations to repeat colonoscopy every 10 years, with the uptake rates of repeat colonoscopy remaining abysmal at 22%. Methods Previously, a qualitative systematic review evaluated the barriers and facilitators patients faced in their decisions to undergo colonoscopy, analyzing articles from Medline, Embase, CINAHL, PsycINFO and Web of Science. Key findings from articles which highlighted factors influencing patients' decisions to return for repeat colonoscopies were summarized. Results Three articles were identified in the search. Facilitators for repeat colonoscopy included patients' assurance garnered from fostered trust in the patient-provider relationship, their intrinsic motivations from fear of cancer and an innate appreciation for the significance of obtaining repeated colonoscopies. Procedural factors such as the option for procedural visualization, its comprehensiveness and the utilization of anesthesia were also crucial motivators. Barriers that patients highlighted comprised of cumbersome bowel preparation and potential complications. Discussion Recently, minimal research has been conducted on the sentiments of healthcare providers and patients regarding repeat colonoscopy. The lack of emphasis from healthcare institutions on encouraging patients to repeat colonoscopy after 10 years prevents effective colorectal cancer screening. To proficiently alleviate the burden of colorectal cancer, patient counseling has to shift beyond explaining colonoscopy risks and complications to promoting regular follow-up scopes. This article thus calls for more studies to focus on evaluating the uptake of repeat colonoscopies.
Published: 2021
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39. Abstract 2258: Germline variants associated with poorer disease prognosis in nasopharyngeal carcinoma

Author: Dewi Susanti, Joseph Wee, Mohamed E. Abazeed, Enya H.W. Ong, Terence W.K. Tan, M.L.K. Chua, Tony Kiat Hon Lim, Jin-Xin Bei, Luo Huang, Kar Perng Low, Yoke Lim Soong, Kam Weng Fong, Darren W. T. Lim, Adelene Y.L. Sim, J.S.G. Hwang, Gek San Tan, and N. Gopalakrishna Iyer
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Nasopharyngeal carcinoma, business.industry, Internal medicine, Medicine, business, medicine.disease, Germline, Disease prognosis
Abstract: Nasopharyngeal carcinoma (NPC) is an endemic disease prevalent in East Asia and germline variants that confer risk for NPC have previously been identified. However, NPC patients have contrasting phenotypes at presentation that are associated with disparate risks of relapse. We hypothesize that there exist germline variants that are associated with poorer NPC disease trajectories. We performed whole exome sequencing (100x; Illumina NovaSeq) on a cohort of 795 NPC patients and probed the germline genomic landscape in a predominantly Chinese population (N=723; 90.9%). We performed univariable and multivariable - adjusting for known prognostic clinical parameters - Cox regression analyses to discover germline variants that were associated with disease-free survival (DFS). We performed joint genotyping of germline variants following GATK's best practices workflow. We next filtered out common (≥5% allele frequency in East Asian population, or ≥1% in others) and benign variants, retaining only variants classified as pathogenic (P)/likely pathogenic (LP)/variant of unknown significance (VUS) in ClinVar or are predicted to be pathogenic by Combined Annotation Dependent Depletion or Rare Exome Variant Ensemble Learner. For improved statistical power, statistical analyses (uni- and multi-variable Cox regression) were conducted at the gene level, so that contributions across all variants were aggregated for each gene. To reduce false discovery, we focused our analysis only on genes of interest: hallmark-of-cancer genes (COSMIC gene census), DNA damage and mismatch repair genes, as well as genes known to be associated with NPC risk. Genes with variants in fewer than 20 unique patients were also excluded from analysis. We observed germline variants in hallmark-of-cancer genes (FAT1 [N=133; 16.7%] and NOTCH1 [N=39; 4.9%]) and DNA repair genes (SRSF6 [N=32; 4.0%] and POLD1 [N=32; 4.0%]). Additionally, 230 (28.9%) and 180 (22.6%) patients had at least one P/LP/VUS variants in HLA-A and HLA-DRB1, consistent with known literature that variants in HLA genes confer increased NPC risk. Likewise, we observed variants in genes associated with NPC risk such as KMT2C (N=207; 26.0%), SYNE1 (N=151; 19.0%), ARID1A (N=52; 6.5%) and MST1R (N=34; 4.3%). Univariable tests of association identified variants in MMP19 (HR 2.24 with 95% confidence interval [1.30-3.87], P=0.004), MST1R (HR 2.01 [1.14-3.54], P=0.016), TGFBR2 (HR 1.85 [1.09-3.14], P=0.023), NEIL3 (HR 2.08 [1.09-3.94], P=0.025), ETV6 (HR 2.13 [1.09-4.16], P=0.028), FANCD2 (HR 2.11 [1.09-4.13], P=0.030), DDX6 (HD 2.26 [1.06-4.82], P=0.035) POLD1 (HR 1.91 [1.04-3.53], P=0.038) and RECQL4 (HR 1.92 [1.04-3.54], P=0.037) that were significantly associated with inferior DFS. Among them, MMP19, TGFBR2, FANCD2 and RECQL4 remained significant in a clinico-molecular multivariable model that comprised of age, sex, cTN-categories, EBV DNA titer and treatment (C-index = 0.71). Citation Format: Adelene Y.L. Sim, Enya H.w. Ong, Luo Huang, Kar Perng Low, Dewi Susanti, Terence W.k. Tan, Kam Weng Fong, Yoke Lim Soong, Gek San Tan, Tony K.H. Lim, Joseph T.s. Wee, Darren W.t. Lim, N. Gopalakrishna Iyer, Jacqueline S.G. Hwang, Mohamed E. Abazeed, Jin-Xin Bei, Melvin L.k. Chua. Germline variants associated with poorer disease prognosis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2258.
Published: 2021
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40. Factors influencing the enrollment in randomized controlled trials in orthopedics

Author: Elena Losina, Christopher T. Lim, Jeffrey N. Katz, Jamie E. Collins, and Heather J. Roberts
Subjects: medicine.medical_specialty, MEDLINE, Psychological intervention, Article, law.invention, External validity, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Medicine, 030212 general & internal medicine, Pharmacology, lcsh:R5-920, business.industry, Orthopedic Surgical Procedure, General Medicine, Clinical trial, Orthopedics, 030220 oncology & carcinogenesis, Orthopedic surgery, Physical therapy, Randomized controlled trials, Recruitment, business, Orthopedic Procedures, lcsh:Medicine (General)
Abstract: Background: Low enrollment rates are a threat to the external validity of clinical trials. The purpose of this study was to identify factors associated with lower enrollment rates in randomized controlled trials (RCTs) involving orthopedic procedures. Methods: We performed a search in PubMed/MEDLINE for RCTs that involved any orthopedic surgical procedure, compared different intraoperative interventions, were published in English in a peer-reviewed journal between 2003 and 2014, and reported the numbers of both enrolled and eligible subjects. The primary outcome was the enrollment rate, defined as the number of enrolled subjects divided by the number of eligible subjects. We used a meta-regression to identify factors associated with lower enrollment rates. Results: The combined estimate of enrollment rate across all 393 studies meeting inclusion criteria was 90% (95% CI: 89–92%). Trials in North America had significantly lower enrollment rates compared to trials in the rest of the world (80% vs. 92%, p
Published: 2017

41. Grading system for migrated lumbar disc herniation on sagittal magnetic resonance imaging: an agreement study

Author: Tae Seok Jeong, Yong Ahn, J Y Jeon, and T Lim
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, 03 medical and health sciences, 0302 clinical medicine, Lumbar, Cohen's kappa, medicine, Humans, Radiology, Nuclear Medicine and imaging, Grading (education), Aged, Neuroradiology, 030222 orthopedics, medicine.diagnostic_test, business.industry, Lumbosacral Region, Magnetic resonance imaging, Middle Aged, Magnetic Resonance Imaging, Sagittal plane, Endoscopic discectomy, Treatment Outcome, medicine.anatomical_structure, Female, Neurology (clinical), Radiology, Lumbar disc herniation, Cardiology and Cardiovascular Medicine, business, Intervertebral Disc Displacement, 030217 neurology & neurosurgery, Diskectomy
Abstract: Migrated lumbar disc herniations (LDHs) in the sagittal plane are common. Disc migration grading can be applied as a useful measurement tool in the diagnosis, treatment, and outcome evaluation of migrated LDH. No study has evaluated the reliability of migrated LDH grading. We evaluated the reliability and functionality of the current magnetic resonance imaging (MRI) grading system for migrated LDH. We assessed a six-level grading system developed based on sagittal MRI and graded according to the direction (rostral and caudal) and degree (low, high, and very high) of disc migration. One-hundred and one migrated LDHs treated with minimally invasive endoscopic discectomy were analyzed independently by two experienced radiologists. Intraobserver and interobserver agreements were assessed by kappa statistics. The most common migrated LDH grade was grade 4 (30.94%; caudal, low-grade migration). Rostral and caudal migrations were more common in the upper and lower lumbar levels, respectively. Interobserver agreement in the grading of migrated LDH was good at both the first (kappa = 0.737) and second assessment (kappa = 0.657). The intraobserver agreement for reader 1 was very good (kappa = 0.827) and for reader 2 was good (kappa = 0.620). The current grading system for migrated LDH was found to be reliable and functional with good interobserver and intraobserver agreement. It may be useful in the interpretation of disc migration patterns and outcomes of various minimally invasive surgical procedures.
Published: 2017
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42. Evaluation of changes in the locomotion and histology of sciatic nerve following experimental autoimmune encephalomyelitis

Author: S. M. W. Chang, Nilesh Kumar Mitra, S. X. Wai, P. Y. Chin, and J. T. Lim
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Histology, business.industry, Experimental autoimmune encephalomyelitis, Cell Biology, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine, Sciatic nerve, Anatomy, business, 030217 neurology & neurosurgery
Abstract: Introduction: Involvement of peripheral nerves in the experimental model of multiple sclerosis (MS) is rarely observed. The objective of this study was to investigate the changes in the locomotion in a mouse model of experimental autoimmune encephalomyelitis (EAE) and correlate with histological changes, if any, in the sections of sciatic nerve and lumbar part of spinal cord. Material and Methods: C57BL/6 mice (10 weeks, n = 8) were immunized with single subcutaneous injection of 300 μg of MOG35-55 and 200 μL of complete Freund's adjuvant (CFA) to produce EAE models. Limp tail with weakness of hindlimb was observed on day 10 and improvement in the weakness was observed on day 20 onwards. Footprint analysis was done to evaluate the impairment in the locomotion on day 0, 5, 10, 15 and 20 of the experiment. Results: One way repeated measure ANOVA found significant reduction in the mean hindlimb stride length on day 10 and 15 (left) and on day 15 and day 20 (right) when compared to mean stride length in day 0 (p
Published: 2017
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43. Qualitative Research in Palliative Care: Applications to Clinical Trials Work

Author: Vicki A. Jackson, Avia Tadmor, Teresa L. Hagan, Daisuke Fujisawa, Jennifer S. Temel, Joseph A. Greer, Elyse R. Park, James J. MacDonald, Christopher T. Lim, Emily R. Gallagher, and Justin Eusebio
Subjects: Adult, Male, Palliative care, Nursing Methodology Research, 03 medical and health sciences, 0302 clinical medicine, Documentation, Nursing, Humans, Medicine, 030212 general & internal medicine, Qualitative Research, General Nursing, Aged, Quality of Health Care, Aged, 80 and over, Clinical Trials as Topic, Descriptive statistics, business.industry, Palliative Care, Original Articles, General Medicine, Focus Groups, Middle Aged, Focus group, Clinical trial, Anesthesiology and Pain Medicine, Work (electrical), Research Design, 030220 oncology & carcinogenesis, Female, Thematic analysis, business, Qualitative research
Abstract: While vast opportunities for using qualitative methods exist within palliative care research, few studies provide practical advice for researchers and clinicians as a roadmap to identify and utilize such opportunities.To provide palliative care clinicians and researchers descriptions of qualitative methodology applied to innovative research questions relative to palliative care research and define basic concepts in qualitative research. Body: We describe three qualitative projects as exemplars to describe major concepts in qualitative analysis of early palliative care: (1) a descriptive analysis of clinician documentation in the electronic health record, (2) a thematic content analysis of palliative care clinician focus groups, and (3) a framework analysis of audio-recorded encounters between patients and clinicians as part of a clinical trial.This study provides a foundation for undertaking qualitative research within palliative care and serves as a framework for use by other palliative care researchers interested in qualitative methodologies.
Published: 2017
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44. Occlusion in the Flow of New Drugs for Cardiovascular Disease

Author: Mathias Baedeker, Najaf A. Shah, Christopher T. Lim, Ulrik Schulze, Michael Ringel, and Aayam Lamichhane
Subjects: Pharmacology, Health Services Needs and Demand, Public investment, Actuarial science, business.industry, Cardiovascular Agents, Disease, 030204 cardiovascular system & hematology, Unmet needs, 03 medical and health sciences, 0302 clinical medicine, Cardiovascular Diseases, Drug Discovery, Occlusion, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, business, Reimbursement, Incentive, Valuation (finance)
Abstract: There is a large misalignment between unmet need and both private and public investment activity in cardiovascular disease. In this paper, we quantify the magnitude of the gap, analyze a range of potential root causes in two main categories (issues of feasibility and valuation), and propose steps toward solutions to close the gap.
Published: 2017
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45. Evaluation of Whole Body DiffusionWeighted Imaging in the Staging and Treatment Response of Lymphoma Compared With Fluoride-Oxyglucose (FDG) PET/CT as a Reference Standard

Author: David Chee Eng Ng, Miriam Tao, S. T Lim, Jin Wei Kwek, Tiffany Priyanthi Hennedige, and Richard Quek
Subjects: Treatment response, medicine.medical_specialty, business.industry, Materials Science (miscellaneous), medicine.disease, Lymphoma, chemistry.chemical_compound, chemistry, medicine, Fdg pet ct, Radiology, Whole body, Nuclear medicine, business, Reference standards, Fluoride
Published: 2017
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46. Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery

Author: Xuan Thang Cao, Hai Ha Pham Thi, K. T. Lim, Y-S. Gal, G-D. Kim, and Cuong M.Q. Le
Subjects: HepG2, Materials science, Polymers and Plastics, General Chemical Engineering, Core (manufacturing), 02 engineering and technology, lcsh:Chemical technology, 010402 general chemistry, digestive system, doxorubicin, 01 natural sciences, Micelle, lcsh:TA401-492, Materials Chemistry, medicine, Ph triggered, lcsh:TP1-1185, Doxorubicin, Physical and Theoretical Chemistry, digestive, oral, and skin physiology, Organic Chemistry, Prodrug, 021001 nanoscience & nanotechnology, Redox responsive, Combinatorial chemistry, digestive system diseases, 0104 chemical sciences, Click chemistry, lcsh:Materials of engineering and construction. Mechanics of materials, Smart polymers, prodrug, 0210 nano-technology, cross-linking, medicine.drug
Abstract: A pH-triggered drug delivery system of degradable core cross-linked (CCL) prodrug micelles was prepared by click chemistry. Doxorubicin conjugated block copolymers of azido functional poly(ethylene oxide)-b-poly(glycidyl methacrylate) were synthesized by the combination of RAFT polymerization, epoxide ring-opening reaction, and acid-cleavable hydrazone linkages. The CCL prodrug micelles were produced by the reaction of dipropargyl 3,3′-dithiodipropionate and dipropargyl adipate cross-linking agents with the azido groups of the micellar core via alkyne-azide click reaction, which were denoted as CCL/SS and CCL/noSS, respectively. The TEM images of CCL/SS prodrug micelles showed a spherical shape with the average diameter of 61.0 nm from water, and the shape was maintained with an increased diameter upon dilution with 5-fold DMF. The high DOX conjugation efficiency was 88.4%. In contrast to a very slow DOX release from CCL/SS prodrug micelles under the physiological condition (pH 7.4), the drug release is much faster (90%) at pH 5.0 and 10 mM of GSH after 96 h. The cytotoxicity test and confocal laser scanning microscopy analysis revealed that CCL/SS prodrug micelles had much enhanced intracellular drug release capability in HepG2 cells than CCL/noSS prodrug micelles.
Published: 2017
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47. 1293P IMpower150: Updated efficacy analysis in patients with EGFR mutations

Author: Francisco Orlandi, Daniil Stroyakovskiy, Gene Grant Finley, Delvys Rodriguez-Abreu, Christian A. Thomas, Denis Moro-Sibilot, Fabrice Barlesi, D. Merritt, Mark A. Socinski, Wei Yu, Robert M. Jotte, Tony Mok, Martin Reck, Frederico Cappuzzo, Geetha Shankar, Makoto Nishio, Naoyuki Nogami, and D.W-T. Lim
Subjects: Oncology, medicine.medical_specialty, business.industry, Egfr mutation, Internal medicine, Medicine, In patient, Hematology, business
Published: 2020
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48. Physician Mental Health: Where to Intervene? A Framework and a Pilot Survey of Psychiatrists

Author: John M Santopietro, Hyong Un, Christopher T Lim, Steven M Kleiner, and J. Wesley Boyd
Subjects: Psychiatry and Mental health, medicine.medical_specialty, Family medicine, medicine, MEDLINE, Pilot survey, General Medicine, Psychology, Mental health, Education
Published: 2020
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49. Rethinking the Thrombophilic Workup a Case of Severe Vitamin B12 Deficiency

Author: T. Lim, S.X. Lee, and J. Lee
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Vitamin B12, business, Gastroenterology
Published: 2019
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50. Improving Enteral Nutrition in the Intensive Care Unit: A Resident-Led Quality Improvement Project

Author: S. Shapiro, T. Lim, J. Lee, and S.X. Lee
Subjects: medicine.medical_specialty, Quality management, Parenteral nutrition, law, business.industry, medicine, Intensive care medicine, business, Intensive care unit, law.invention
Published: 2019
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