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1,935 results on '"Kearns, A"'

1. Breaking Down the Bottlebrush: Atomically Detailed Structural Dynamics of Mucins.

Author

Kearns, Fiona, Rosenfeld, Mia, and Amaro, Rommie

Subjects
Molecular Dynamics Simulation, Mucins, Protein Conformation, Glycosylation, Humans, Mucin-5B
Abstract

Mucins, the biomolecular components of mucus, are glycoproteins that form a thick physical barrier at all tissue-air interfaces, forming a first line of defense against pathogens. Structural features of mucins and their interactions with other biomolecules remain largely unexplored due to the challenges associated with their high-resolution characterization. Combining limited mass spectrometry glycomics and protein sequencing data, we present all-atom, explicitly solvated molecular dynamics simulations of a major respiratory mucin, MUC5B. We detail key forces and degrees of freedom imposed by the extensive O-glycosylation, which imbue the canonically observed bottlebrush-like structures to these otherwise intrinsically disordered protein backbones. We compare our simulation results to static structures observed in recent scanning tunneling microscopy experiments as well as other published experimental efforts. Our work represents the demonstration of a workflow applied to a mucin example, which we hope will be employed by other groups to investigate the dynamics and interactions of other mucins, which can inform on structural details currently inaccessible to experimental techniques.

Published
2024

2. Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens.

Author

Nuqui, Xandra, Casalino, Lorenzo, Zhou, Ling, Shehata, Mohamed, Wang, Albert, Tse, Alexandra, Ojha, Anupam, Kearns, Fiona, Rosenfeld, Mia, Miller, Emily, Acreman, Cory, Ahn, Shirley, Chandran, Kartik, McLellan, Jason, and Amaro, Rommie

Subjects
Spike Glycoprotein, Coronavirus, SARS-CoV-2, Humans, COVID-19 Vaccines, Molecular Dynamics Simulation, COVID-19, Cryoelectron Microscopy, Protein Stability, Antibodies, Neutralizing, Antibodies, Viral, Animals
Abstract

The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimers opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

Published
2024

3. Teletherapy to address language disparities in deaf and hard-of-hearing children: study protocol for an inclusive multicentre clinical trial.

Author

Naugle, Kendyl, Stephans, Jihyun, Lazar, Ann, Kearns, Joy, Coulthurst, Sarah, Tebb, Kathleen, and Chan, Dylan

Subjects
audiology, paediatric otolaryngology, telemedicine, Humans, Deafness, Child, Preschool, Infant, Persons With Hearing Impairments, Infant, Newborn, Language Development Disorders, Healthcare Disparities, Randomized Controlled Trials as Topic, Female, Speech Therapy, Multicenter Studies as Topic, Language Therapy, Male, Prospective Studies, Research Design, Health Services Accessibility, Quality of Life
Abstract

INTRODUCTION: Children who are deaf or hard-of-hearing (DHH) are at risk for speech and language delay. Language outcomes are worse in DHH children from lower socioeconomic backgrounds, due in part to disparities in access to specialised speech-language therapy. Teletherapy may help improve access to this specialised care and close this language gap. Inclusion of diverse DHH children in prospective randomised clinical trials has been challenging but is necessary to address disparities and pursue hearing health equity. Stakeholder input regarding decisions on study design elements, including comparator groups, masking, assessments and compensation, is necessary to design inclusive studies. We have designed an inclusive, equitable comparativeness effectiveness trial to address disparities in paediatric hearing health. The specific aims of the study are to determine the effect of access to and utilisation of speech-language teletherapy in addressing language disparities in low-income children who are DHH. METHODS AND ANALYSIS: After stakeholder input and pilot data collection, we designed a randomised clinical trial and concurrent longitudinal cohort trial to be conducted at four tertiary childrens hospitals in the USA. Participants will include 210 DHH children aged 0-27 months. 140 of these children will be from lower income households, who will be randomised 1:1 to receive usual care versus usual care plus access to supplemental speech-language teletherapy. 70 children from higher income households will be simultaneously recruited as a comparison cohort. Primary outcome measure will be the Preschool Language Scales Auditory Comprehension subscale standard score, with additional speech, language, hearing and quality of life validated measures as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards of the participating sites: the University of California, San Francisco (19-28356), Rady Childrens Hospital (804651) and Seattle Childrens Hospital (STUDY00003750). Parents of enrolled children will provide written informed consent for their childs participation. Professional and parent stakeholder groups that have been involved throughout the study design will facilitate dissemination and implementation of study findings via publication and through national and regional organisations. TRIAL REGISTRATION NUMBER: NCT04928209.

Published
2024

4. Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

Author

Moghadasi, Seyed Arad, Heilmann, Emmanuel, Khalil, Ahmed Magdy, Nnabuife, Christina, Kearns, Fiona L, Ye, Chengjin, Moraes, Sofia N, Costacurta, Francesco, Esler, Morgan A, Aihara, Hideki, von Laer, Dorothee, Martinez-Sobrido, Luis, Palzkill, Timothy, Amaro, Rommie E, and Harris, Reuben S

Subjects
Lung, Pneumonia, Pneumonia & Influenza, Prevention, Emerging Infectious Diseases, Vaccine Related, Antimicrobial Resistance, Biodefense, Infectious Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Humans, SARS-CoV-2, COVID-19, Protease Inhibitors, Phylogeny, Peptide Hydrolases
Abstract

Vaccines and drugs have helped reduce disease severity and blunt the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease [Mpro; 3C-like protease (3CLpro)] of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.

Published
2023

5. Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection

Author

Oh, Chang-ki, Nakamura, Tomohiro, Beutler, Nathan, Zhang, Xu, Piña-Crespo, Juan, Talantova, Maria, Ghatak, Swagata, Trudler, Dorit, Carnevale, Lauren N, McKercher, Scott R, Bakowski, Malina A, Diedrich, Jolene K, Roberts, Amanda J, Woods, Ashley K, Chi, Victor, Gupta, Anil K, Rosenfeld, Mia A, Kearns, Fiona L, Casalino, Lorenzo, Shaabani, Namir, Liu, Hejun, Wilson, Ian A, Amaro, Rommie E, Burton, Dennis R, Yates, John R, Becker, Cyrus, Rogers, Thomas F, Chatterjee, Arnab K, and Lipton, Stuart A

Subjects
Vaccine Related, Emerging Infectious Diseases, Prevention, Pneumonia & Influenza, Biodefense, Pneumonia, Infectious Diseases, Lung, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Angiotensin-Converting Enzyme 2, Protein Binding, Peptidyl-Dipeptidase A, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Biochemistry & Molecular Biology
Abstract

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.

Published
2023

6. Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies

Author

Goodman, Daniel B, Azimi, Camillia S, Kearns, Kendall, Talbot, Alexis, Garakani, Kiavash, Garcia, Julie, Patel, Nisarg, Hwang, Byungjin, Lee, David, Park, Emily, Vykunta, Vivasvan S, Shy, Brian R, Ye, Chun Jimmie, Eyquem, Justin, Marson, Alexander, Bluestone, Jeffrey A, and Roybal, Kole T

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Health Disparities, Genetics, Minority Health, Gene Therapy, Cancer, Biotechnology, Immunotherapy, 5.2 Cellular and gene therapies, Inflammatory and immune system, Humans, Neoplasm Recurrence, Local, B-Cell Maturation Antigen, Receptors, Chimeric Antigen, Immunotherapy, Adoptive, T-Lymphocytes, Signal Transduction, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure. Several domains were identified from the tumor necrosis factor (TNF) receptor family that have been primarily associated with B cells. CD40 enhanced proliferation, whereas B cell-activating factor receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) promoted cytotoxicity. These functions were enhanced relative to clinical benchmarks after prolonged antigen stimulation, and CAR T cell signaling through these domains fell into distinct states of memory, cytotoxicity, and metabolism. BAFF-R CAR T cells were enriched for a highly cytotoxic transcriptional signature previously associated with positive clinical outcomes. We also observed that replacing the 4-1BB intracellular signaling domain with the BAFF-R signaling domain in a clinically validated B cell maturation antigen (BCMA)-specific CAR resulted in enhanced activity in a xenotransplant model of multiple myeloma. Together, these results show that CAR Pooling is a general approach for rapid exploration of CAR architecture and activity to improve the efficacy of CAR T cell therapies.

Published
2022

7. Spike-heparan sulfate interactions in SARS-CoV-2 infection

Author

Kearns, Fiona L, Sandoval, Daniel R, Casalino, Lorenzo, Clausen, Thomas M, Rosenfeld, Mia A, Spliid, Charlotte B, Amaro, Rommie E, and Esko, Jeffrey D

Subjects
Pneumonia & Influenza, Emerging Infectious Diseases, Vaccine Related, Lung, Biodefense, Prevention, Infectious Diseases, Pneumonia, Infection, Angiotensin-Converting Enzyme 2, Asparagine, Binding Sites, COVID-19, Heparitin Sulfate, Humans, Protein Binding, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Biophysics
Abstract

Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection of SARS-CoV-2 by facilitating the so-called open conformation of the spike protein, which is required for binding to ACE2. This review highlights the involvement of heparan sulfate in the SARS-CoV-2 infection cycle and argues that there is a high degree of coordination between host cell heparan sulfate and asparagine-linked glycans on the spike in enabling ACE2 binding and subsequent infection. The discovery that spike protein binding and infection depends on both viral and host glycans provides insights into the evolution, spread and potential therapies for SARS-CoV-2 and its variants.

Published
2022

8. FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis

Author

Kearns, Patrick KA, Martin, Sarah J, Chang, Jessie, Meijboom, Rozanna, York, Elizabeth N, Chen, Yingdi, Weaver, Christine, Stenson, Amy, Hafezi, Katarzyna, Thomson, Stacey, Freyer, Elizabeth, Murphy, Lee, Harroud, Adil, Foley, Peter, Hunt, David, McLeod, Margaret, O'Riordan, Jonathon, Carod-Artal, FJ, MacDougall, Niall JJ, Baranzini, Sergio E, Waldman, Adam D, Connick, Peter, and Chandran, Siddharthan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Autoimmune Disease, Clinical Research, Neurosciences, Neurodegenerative, Multiple Sclerosis, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Good Health and Well Being, Adult, Biomarkers, Cohort Studies, Disease Progression, Humans, Multiple Sclerosis, Relapsing-Remitting, Prospective Studies, neurology, epidemiology, neurogenetics, multiple sclerosis, neuroradiology, internal medicine, Public Health and Health Services, Other Medical and Health Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

PurposeMultiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate or aggressive disease course is very limited. There is, therefore, a need for integrated predictive tools to inform individualised treatment decision making.ParticipantsEstablished with the aim of addressing this need for individualised predictive tools, FutureMS is a nationally representative, prospective observational cohort study of 440 adults with a new diagnosis of relapsing-remitting MS living in Scotland at the time of diagnosis between May 2016 and March 2019.Findings to dateThe study aims to explore the pathobiology and determinants of disease heterogeneity in MS and combines detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow-up at year 1 is complete. Here, we describe the cohort design and present a profile of the participants at baseline and 1 year of follow-up.Future plansA third follow-up wave for the cohort has recently begun at 5 years after first visit and a further wave of follow-up is funded for year 10. Longer-term follow-up is anticipated thereafter.

Published
2022

9. Dominant Power and the Concept of Caste: Implications for Dentistry and Oral Health Inequality.

Author

Kearns, C, Taylor, G, Oberoi, S, and Mertz, E

Subjects
Dental Societies, Dentists, Oral Health, Racism, Dentistry, Health Status Disparities, Humans, Oral Health, Racism, Social Class, Socioeconomic Factors, United States
Abstract

This paper explores the issues of caste and casteism in the U.S. as described by Pulitzer Prize winning journalist Isabel Wilkerson in her 2020 book Caste: The Origin of Our Discontents. Wilkerson argues that a caste system not only exists in the U.S. but operates as a hidden force affecting social inequality. The paper draws on Wilkersons work to explore caste as an analytical concept. It begins by defining caste and casteism in contrast with racism, the eight pillars of a caste system, the consequences of casteism, and the psychological drivers of casteism. The paper then applies to concept of caste to understanding power, dentistry, and oral health inequality. The paper concludes by emphasizing that the concept of caste and its relationship to oral health inequality must be understood it if we want to create real social change.

Published
2022

10. California Dentists’ Engagement in Media Advocacy for Sugar Restriction Policies

Author

Kearns, CE, Urata, J, and Chaffee, BW

Subjects
Dental/Oral and Craniofacial Disease, Behavioral and Social Science, Prevention, Basic Behavioral and Social Science, Prevention of disease and conditions, and promotion of well-being, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Oral and gastrointestinal, Quality Education, Good Health and Well Being, Dental Caries, Dentists, Humans, Policy, Sugars, Surveys and Questionnaires, role of dentist, sugars, diet, surveys, dental caries, nutrition policy
Abstract

ObjectivesIncreasing dentists' visibility in the media to make the case for sugary beverage taxes can help advance public policy that improves oral health outcomes. We assessed California dentists' media engagement behaviors related to sugar restriction policies for dental caries prevention and correlates of engaging in such behavior.MethodsSurvey items related to sugar policies and media engagement were embedded in an electronically distributed statewide survey of dentists' tobacco cessation counseling behaviors. Descriptive statistics were calculated for respondent characteristics, perceived professional responsibility to discuss selected topics with patients, and attitudes and behaviors related to sugar restriction policy and media communication. Multivariable models identified independent correlates of media engagement.ResultsOf 624 respondents, most had never talked to traditional media (78%) or posted to social media (64%) about sugar or sugar policies for dental caries prevention. Respondents with the highest level of media engagement were more likely to agree that sugary beverage taxes are effective at reducing dental caries, that they had support from dental professional organizations to talk to the media, that it is realistic for patients to reduce their sugar consumption, and that sugar and sugary drinks are extremely harmful to health.ConclusionsEfforts to increase dentists' media engagement related to sugar restriction policies for dental caries prevention should address dentists' negative attitudes toward the effectiveness of sugar restriction policies and may require increased support from dental professional societies.Knowledge transfer statementStudy findings identify dentists' low engagement in media advocacy to support sugar restriction policy adoption. The results identify correlates of media engagement and of dentists' willingness and confidence to act, which could serve to inform interventions to support and enhance engagement.

Published
2022

11. Work site access to fluoridated tap water and retail beverages An assessment of the University of California, San Francisco campuses

Author

Kalair, Navita, Mousli, Leyla M, Jacobs, Laurie M, Schmidt, Laura, and Kearns, Cristin

Subjects
Biomedical and Clinical Sciences, Dentistry, Clean Water and Sanitation, Beverages, Drinking Water, Humans, San Francisco, Workplace, fluoridation, health promotion, occupation health
Abstract

BackgroundEmployees with fluoridated drinking water access at work can reap oral health benefits. The purpose of this study was to assess the availability, appeal, and promotion of fluoridated tap water in publicly accessible spaces compared with retail beverages at the University of California, San Francisco.MethodsThe authors collected information on beverages available in publicly accessible spaces at University of California, San Francisco hospitals and campuses in San Francisco, California, from December 2019 through February 2020 using a web-based survey tool. Data collected included fluoridated water and retail beverage locations; type of water or retail beverage source; number of water sources per station; cleanliness, flow, and any obstruction of water sources; proximity of water stations to retail beverage locations; signage near the beverage locations about water and beverage consumption; and type of retail beverages available.ResultsFluoridated water stations were identified in 230 locations and had 377 water sources (for example, traditional drinking fountain and motion-sensor bottle-filling station). One water station was available for every 80 students and employees; however, 25% were obstructed, dirty, or had unsatisfactory flow. Approximately 1 in 5 watercoolers lacked disposable cups. Of 41 retail beverage locations identified, 29% had a water station within sight. Only 11% of beverage locations had signage encouraging healthier beverage choices.ConclusionsA systematic assessment of work site access to fluoridated water can provide actionable evidence to improve availability, appeal, and promotion.Practical implicationsThis study provides a model to assess work site availability of fluoridated drinking water that can be used for future evaluations.

Published
2022

12. In vitro propagation of XXY human Klinefelter spermatogonial stem cells: A step towards new fertility opportunities

Author

Galdon, Guillermo, Deebel, Nicholas A, Zarandi, Nima Pourhabibi, Teramoto, Darren, Lue, YanHe, Wang, Christina, Swerdloff, Ronald, Pettenati, Mark J, Kearns, William G, Howards, Stuart, Kogan, Stanley, Atala, Anthony, and Sadri-Ardekani, Hooman

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Transplantation, Biotechnology, Contraception/Reproduction, Adolescent, Humans, Integrin alpha6, Klinefelter Syndrome, Male, Spermatogenesis, Spermatogonia, Stem Cells, Testis, spermatogonia, stem cell, germ cell transplantation, fertility preservation, male infertility, cell culture, Clinical Sciences, Nutrition and Dietetics, Clinical sciences
Abstract

Klinefelter Syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (47, XXY), and impaired fertility due to loss of spermatogonial stem cells (SSCs). Early testicular cryopreservation could be an option for future fertility treatments in these patients, including SSCs transplantation or in vitro spermatogenesis. It is critically essential to adapt current in vitro SSCs propagation systems as a fertility option for KS patients. KS human testicular samples (13,15- and 17-year-old non-mosaic KS boys) were donated by patients enrolled in an experimental testicular tissue banking program. Testicular cells were isolated from cryopreserved tissue and propagated in long-term culture for 110 days. Cell-specific gene expression confirmed the presence of all four main cell types found in testes: Spermatogonia, Sertoli, Leydig, and Peritubular cells. A population of ZBTB16+ undifferentiated spermatogonia was identified throughout the culture using digital PCR. Flow cytometric analysis also detected an HLA-/CD9+/CD49f+ population, indicating maintenance of a stem cell subpopulation among the spermatogonial cells. FISH staining for chromosomes X and Y showed most cells containing an XXY karyotype with a smaller number containing either XY or XX. Both XY and XX populations were able to be enriched by magnetic sorting for CD9 as a spermatogonia marker. Molecular karyotyping demonstrated genomic stability of the cultured cells, over time. Finally, single-cell RNAseq analysis confirmed transcription of ID4, TCN2, and NANOS 3 within a population of putative SSCs population. This is the first study showing successful isolation and long-term in vitro propagation of human KS testicular cells. These findings could inform the development of therapeutic fertility options for KS patients, either through in vitro spermatogenesis or transplantation of SSC, in vivo.

Published
2022

13. A glycan gate controls opening of the SARS-CoV-2 spike protein

Author

Sztain, Terra, Ahn, Surl-Hee, Bogetti, Anthony T, Casalino, Lorenzo, Goldsmith, Jory A, Seitz, Evan, McCool, Ryan S, Kearns, Fiona L, Acosta-Reyes, Francisco, Maji, Suvrajit, Mashayekhi, Ghoncheh, McCammon, J Andrew, Ourmazd, Abbas, Frank, Joachim, McLellan, Jason S, Chong, Lillian T, and Amaro, Rommie E

Subjects
Infectious Diseases, Biodefense, Prevention, Pneumonia, Lung, Emerging Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, Aetiology, Cryoelectron Microscopy, Humans, Molecular Dynamics Simulation, Polysaccharides, Spike Glycoprotein, Coronavirus, Chemical Sciences, Organic Chemistry
Abstract

SARS-CoV-2 infection is controlled by the opening of the spike protein receptor binding domain (RBD), which transitions from a glycan-shielded 'down' to an exposed 'up' state to bind the human angiotensin-converting enzyme 2 receptor and infect cells. While snapshots of the 'up' and 'down' states have been obtained by cryo-electron microscopy and cryo-electron tomagraphy, details of the RBD-opening transition evade experimental characterization. Here over 130 µs of weighted ensemble simulations of the fully glycosylated spike ectodomain allow us to characterize more than 300 continuous, kinetically unbiased RBD-opening pathways. Together with ManifoldEM analysis of cryo-electron microscopy data and biolayer interferometry experiments, we reveal a gating role for the N-glycan at position N343, which facilitates RBD opening. Residues D405, R408 and D427 also participate. The atomic-level characterization of the glycosylated spike activation mechanism provided herein represents a landmark study for ensemble pathway simulations and offers a foundation for understanding the fundamental mechanisms of SARS-CoV-2 viral entry and infection.

Published
2021

14. Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature

Author

Luu, Irene, Nation, Javan, Page, Nathan, Carvalho, Daniela, Magit, Anthony, Jiang, Wen, Leuin, Shelby, Bliss, Morgan, Bothwell, Marcella, Brigger, Matthew, Kearns, Donald, Pransky, Seth, and Broderick, Lori

Subjects
Digestive Diseases, Pediatric, Dental/Oral and Craniofacial Disease, Pain Research, CD3 Complex, Child, Preschool, Female, Fever, Gastrointestinal Diseases, Hereditary Autoinflammatory Diseases, Humans, Inflammation, Interleukin-1, Lymphadenitis, Male, Palatine Tonsil, Pediatrics, Pharyngitis, Stomatitis, Aphthous, Syndrome, T-Lymphocytes, Tonsillectomy, Recurrent fever, Periodic fever, Autoinflammation, Immunology
Abstract

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

Published
2021

15. Beverage Advertisement Receptivity Associated With Sugary Drink Intake and Harm Perceptions Among California Adolescents

Author

Chaffee, Benjamin W, Werts, Miranda, White, Justin S, Couch, Elizabeth T, Urata, Janelle, Cheng, Jing, and Kearns, Cristin

Subjects
Public Health, Health Sciences, Clinical Research, Pediatric, Adolescent, Advertising, Beverages, California, Cross-Sectional Studies, Humans, Perception, Sugars, Sweetening Agents, adolescent health, sugar-sweetened beverages, marketing, risk perceptions, nutrition, health behaviors, Human Movement and Sports Sciences, Public Health and Health Services, Curriculum and Pedagogy, Public health
Abstract

PurposeEvaluate associations of adolescents' beverage marketing receptivity with sugar-sweetened beverage (SSB) perceived harm and intake.DesignSchool-based cross-sectional health behavior survey.SettingSeven rural schools in California, 2019-2020.Subjects815 student participants in grades 9 or 10.MeasuresParticipants viewed 6 beverage advertisement images with brand obscured, randomly selected from a larger pool. Ads for telecommunications products were an internal control. Receptivity was a composite of recognizing, liking, and identifying the displayed brand (later categorized: low, moderate, high). Weekly SSB servings were measured with a quantitative food frequency questionnaire and perceived SSB harm as 4 levels ("no harm" to "a lot").AnalysisOutcomes SSB intake (binomial regression) and perceived harm (ordered logistic regression) were modeled according to advertisement receptivity (independent variable), with multiple imputation, school-level clustering, and adjustment for presumed confounders (gender, age, screen time, etc.).ResultsIn covariable-adjusted models, greater beverage advertisement receptivity independently predicted higher SSB intake (ratio of SSB servings, high vs. low receptivity: 1.48 [95% CI: 1.15, 1.89]) and lower perceived SSB harm (odds ratio, high vs. low receptivity: 0.59 [0.40, 0.88]). Perceived SSB harm was inversely associated with SSB intake.ConclusionBeverage advertisement receptivity was associated with less perceived SSB harm and greater SSB consumption in this population. Policy strategies, including marketing restrictions or counter-marketing campaigns could potentially reduce SSB consumption and improve health.

Published
2021

16. Actionable, Revised (v.3), and Amplified American Burn Association Triage Tables for Mass Casualties: A Civilian Defense Guideline.

Author

Kearns, Randy D, Bettencourt, Amanda P, Hickerson, William L, Palmieri, Tina L, Biddinger, Paul D, Ryan, Colleen M, and Jeng, James C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Physical Injury - Accidents and Adverse Effects, Clinical Research, Health and social care services research, 8.1 Organisation and delivery of services, Good Health and Well Being, Burns, Disaster Planning, Humans, Mass Casualty Incidents, Surge Capacity, Triage, United States, Emergency & Critical Care Medicine, Clinical sciences, Allied health and rehabilitation science, Nursing
Abstract

Burn care remains among the most complex of the time-sensitive treatment interventions in medicine today. An enormous quantity of specialized resources are required to support the critical and complex modalities needed to meet the conventional standard of care for each patient with a critical burn injury. Because of these dependencies, a sudden surge of patients with critical burn injuries requiring immediate and prolonged care following a burn mass casualty incident (BMCI) will place immense stress on healthcare system assets, including supplies, space, and an experienced workforce (staff). Therefore, careful planning to maximize the efficient mobilization and rational use of burn care resources is essential to limit morbidity and mortality following a BMCI. The U.S. burn care profession is represented by the American Burn Association (ABA). This paper has been written by clinical experts and led by the ABA to provide further clarity regarding the capacity of the American healthcare system to absorb a surge of burn-injured patients. Furthermore, this paper intends to offer responders and clinicians evidence-based tools to guide their response and care efforts to maximize burn care capabilities based on realistic assumptions when confronted with a BMCI. This effort also aims to align recommendations in part with those of the Committee on Crisis Standards of Care for the Institute of Medicine, National Academies of Sciences. Their publication guided the work in this report, identified here as "conventional, contingency, and crisis standards of care." This paper also includes an update to the burn Triage Tables- Seriously Resource-Strained Situations (v.2).

Published
2020

17. Transnational corporations, obesity and planetary health

Author

Schmidt, Laura, Mialon, Melissa, Kearns, Cristin, and Crosbie, Eric

Subjects
Climate Change Impacts and Adaptation, Environmental Management, Environmental Sciences, Public Health, Health Sciences, Commerce, Global Health, Humans, Internationality, Obesity, Climate change impacts and adaptation, Environmental management, Public health
Published
2020

18. Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Author

Luu, Irene, Sharma, Anukriti, Guaderrama, Marisela, Peru, Michelle, Nation, Javan, Page, Nathan, Carvalho, Daniela, Magit, Anthony, Jiang, Wen, Leuin, Shelby, Bliss, Morgan, Bothwell, Marcella, Brigger, Matthew, Kearns, Donald, Newbury, Robert, Pransky, Seth, Gilbert, Jack A, and Broderick, Lori

Subjects
CD8-Positive T-Lymphocytes, Cell Line, Humans, Stomatitis, Aphthous, Pharyngitis, Lymphadenitis, Syndrome, Inflammation, Fever, Tonsillectomy, Adolescent, Child, Child, Preschool, Infant, Female, Male, Palatine Tonsil, Cellular Microenvironment, Autoinflammation, Microbiome, Pediatrics, Periodic fever, Clinical Research, Pediatric, Dental/Oral and Craniofacial Disease, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Immunology
Abstract

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p

Published
2020

19. Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study

Author

Jayawardena, Eranthi, Li, Dong, Nakanishi, Rine, Dey, Damini, Dailing, Christopher, Qureshi, Assad, Dickens, Brooke, Hathiramani, Nicolai, Kim, Michael, Flores, Ferdinand, Kearns, Ann E, Lui, Li-Yung, Black, Dennis, and Budoff, Matthew J

Subjects
Information and Computing Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Software Engineering, Cardiovascular, Bioengineering, Prevention, Heart Disease, Biomedical Imaging, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adipose Tissue, Adiposity, Female, Healthy Volunteers, Humans, Menopause, Middle Aged, Observer Variation, Pericardium, Predictive Value of Tests, Radiographic Image Interpretation, Computer-Assisted, Radiography, Thoracic, Reproducibility of Results, Retrospective Studies, Tomography, X-Ray Computed, United States, Epicardial fat volume, intra-thoracic fat volume, computed tomography, intra-observer, inter-observer, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Applied computing
Abstract

BackgroundCardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software.MethodsWe used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type.ResultsThe intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm3) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm3) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p

Published
2020

20. Supporting elimination of lymphatic filariasis in Samoa by predicting locations of residual infection using machine learning and geostatistics

Author

Mayfield, Helen J, Sturrock, Hugh, Arnold, Benjamin F, Andrade-Pacheco, Ricardo, Kearns, Therese, Graves, Patricia, Naseri, Take, Thomsen, Robert, Gass, Katherine, and Lau, Colleen L

Subjects
Clinical Research, Infectious Diseases, Vector-Borne Diseases, Infection, Good Health and Well Being, Aedes, Animals, Antibodies, Helminth, Antigens, Helminth, Brugia malayi, Disease Reservoirs, Elephantiasis, Filarial, Epidemiological Monitoring, Family Characteristics, Humans, Insect Vectors, Machine Learning, Prevalence, Samoa, Wuchereria bancrofti
Abstract

The global elimination of lymphatic filariasis (LF) is a major focus of the World Health Organization. One key challenge is locating residual infections that can perpetuate the transmission cycle. We show how a targeted sampling strategy using predictions from a geospatial model, combining random forests and geostatistics, can improve the sampling efficiency for identifying locations with high infection prevalence. Predictions were made based on the household locations of infected persons identified from previous surveys, and environmental variables relevant to mosquito density. Results show that targeting sampling using model predictions would have allowed 52% of infections to be identified by sampling just 17.7% of households. The odds ratio for identifying an infected individual in a household at a predicted high risk compared to a predicted low risk location was 10.2 (95% CI 4.2-22.8). This study provides evidence that a 'one size fits all' approach is unlikely to yield optimal results when making programmatic decisions based on model predictions. Instead, model assumptions and definitions should be tailored to each situation based on the objective of the surveillance program. When predictions are used in the context of the program objectives, they can result in a dramatic improvement in the efficiency of locating infected individuals.

Published
2020

21. In defense of sugar: a critical analysis of rhetorical strategies used in The Sugar Association’s award-winning 1976 public relations campaign

Author

Kearns, Cristin E, Glantz, Stanton A, and Apollonio, Dorie E

Subjects
Epidemiology, Health Services and Systems, Public Health, Health Sciences, Nutrition, Metabolic and endocrine, Awards and Prizes, Dietary Sugars, Food Industry, Humans, Noncommunicable Diseases, Nutrition Policy, Persuasive Communication, Public Relations, United States, Sugar industry, Crisis communication, Corporate apologia, Non-communicable diseases, Public Health and Health Services, Health services and systems, Public health
Abstract

BackgroundIn 1976, the U.S. Sugar Association (SA), a globally networked trade organization representing the cane and beet sugar industry, won the Public Relations Society of America's (PRSA) Silver Anvil Award for a crisis communication campaign. Their campaign successfully limited the diffusion of sugar restriction policies to control obesity, heart disease, diabetes, and dental caries, and marked the beginning of the modern-day SA. The sugar industry continues to resist measures to reduce sugar consumption, therefore understanding and addressing industry opposition is crucial to achieving global targets to reduce non-communicable disease.MethodsWe critically analyze common crisis management rhetorical strategies used by SA to defend itself from perceived wrongdoing, and sugar from perceptions of harm using a thematic content analysis based on Hearit's Corporate Apologia theory. Data sources were internal SA documents related to the 1976 Silver Anvil Award in 1) PRSA records, 2) Great Western Sugar Company records, and 3) William Jefferson Darby Papers.ResultsSA, using prototypical apologia stances (counterattack, differentiation, apology, and corrective action) and rhetorical dissociation strategies (appearance/reality, opinion/knowledge, and act/essence) constructed a persuasive narrative to successfully defend sugar from a product safety crisis, and the sugar industry from a social legitimacy crisis. SA's overarching narrative was that restricting sugar, which it claimed was a valuable food that makes healthy foods more palatable, would cause harm and that claims to the contrary were made by opportunists, pseudoscientists, food-faddists, lay nutritionists or those who had been misled by them. SA's apologia does not meet criteria for truthfulness or sincerity.ConclusionCorporate apologia theory provides an accessible way of understanding sugar industry crisis communication strategies. It enables public health actors to recognize and predict industry corporate apologia in response to ongoing product safety and social legitimacy challenges. Industry counterarguments can be examined for truthfulness and sincerity (or the lack thereof), and explained to policymakers considering sugar restriction policies, and to the public, thereby decreasing the effectiveness of illegitimate industry communication efforts to oppose regulation and legislation.

Published
2019

22. BPG: Seamless, automated and interactive visualization of scientific data

Author

P’ng, Christine, Green, Jeffrey, Chong, Lauren C, Waggott, Daryl, Prokopec, Stephenie D, Shamsi, Mehrdad, Nguyen, Francis, Mak, Denise YF, Lam, Felix, Albuquerque, Marco A, Wu, Ying, Jung, Esther H, Starmans, Maud HW, Chan-Seng-Yue, Michelle A, Yao, Cindy Q, Liang, Bianca, Lalonde, Emilie, Haider, Syed, Simone, Nicole A, Sendorek, Dorota, Chu, Kenneth C, Moon, Nathalie C, Fox, Natalie S, Grzadkowski, Michal R, Harding, Nicholas J, Fung, Clement, Murdoch, Amanda R, Houlahan, Kathleen E, Wang, Jianxin, Garcia, David R, de Borja, Richard, Sun, Ren X, Lin, Xihui, Chen, Gregory M, Lu, Aileen, Shiah, Yu-Jia, Zia, Amin, Kearns, Ryan, and Boutros, Paul C

Subjects
Information and Computing Sciences, Applied Computing, Networking and Information Technology R&D (NITRD), Data Analysis, Humans, Simulation Training, Software, Data-visualization, Interactive plotting, Web-resources, Mathematical Sciences, Biological Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

BackgroundWe introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment.ResultsThis open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines.ConclusionBPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.

Published
2019

23. A 2019 reproductive update from the Midwest Reproductive Symposium International

Author

Zolton, Jessica R, Collins, Gretchen G, Greenwood, Eleni A, Hobeika, Elie, Jeelani, Roohi, Beltsos, Angeline, and Kearns, William G

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Contraception/Reproduction, Infertility, Reproductive health and childbirth, Good Health and Well Being, Congresses as Topic, Humans, Physicians, Reproduction, infertility, genetics, reproductive endocrinology, continuing medical education, medical conference, Genetics, Paediatrics and Reproductive Medicine, Obstetrics & Reproductive Medicine, Reproductive medicine
Abstract

"Mystery, Medicine, and the Magnificent Mile," the theme for the annual Midwest Reproductive Symposium International (MRSi) in Chicago, IL, captured the attention of reproductive professionals all over the world. Each year, the conference agenda encompasses emerging technologies in assisted reproduction, updates in the management of reproductive diseases, and common challenges encountered in clinical practice. The structure of the meeting, offering a mixture of lectures, panel discussions, and interactive workshops, creates a collaborative environment for physicians, geneticists, embryologists, nurses, mental health professionals, basic scientists, business administrative professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents. The goal of the MRSi meeting is to provide all reproductive professionals the opportunity to exchange ideas, foster relationships, and deliver quality patient care. As the field continues to evolve, MRSi provides an exciting venue to uncover the mysteries of reproductive medicine with enthusiasm and collaboration.

Published
2019

24. Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial

Author

Khoudary, Samar R El, Zhao, Qian, Venugopal, Vidya, Manson, JoAnn E, Brooks, Maria M, Santoro, Nanette, Black, Dennis M, Harman, S Mitchell, Cedars, Marcelle I, Hopkins, Paul N, Kearns, Ann E, Miller, Virginia M, Taylor, Hugh S, and Budoff, Matthew J

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Heart Disease, Prevention, Clinical Research, Clinical Trials and Supportive Activities, Heart Disease - Coronary Heart Disease, Estrogen, Cardiovascular, Aging, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adipose Tissue, Coronary Artery Disease, Disease Progression, Estradiol, Estrogen Replacement Therapy, Estrogens, Estrogens, Conjugated (USP), Female, Humans, Middle Aged, Pericardium, Vascular Calcification, coronary artery disease, epicardial fat, estrogen, menopause, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and

Published
2019

25. Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial.

Author

El Khoudary, Samar R, Zhao, Qian, Venugopal, Vidya, Manson, JoAnn E, Brooks, Maria M, Santoro, Nanette, Black, Dennis M, Harman, S Mitchell, Cedars, Marcelle I, Hopkins, Paul N, Kearns, Ann E, Miller, Virginia M, Taylor, Hugh S, and Budoff, Matthew J

Subjects
Pericardium, Adipose Tissue, Humans, Disease Progression, Estradiol, Estrogens, Conjugated (USP), Estrogens, Estrogen Replacement Therapy, Middle Aged, Female, Coronary Artery Disease, Vascular Calcification, coronary artery disease, epicardial fat, estrogen, menopause, Conjugated, Cardiorespiratory Medicine and Haematology
Abstract

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and

Published
2019

26. BPG: Seamless, automated and interactive visualization of scientific data.

Author

P'ng, Christine, Green, Jeffrey, Chong, Lauren C, Waggott, Daryl, Prokopec, Stephenie D, Shamsi, Mehrdad, Nguyen, Francis, Mak, Denise YF, Lam, Felix, Albuquerque, Marco A, Wu, Ying, Jung, Esther H, Starmans, Maud HW, Chan-Seng-Yue, Michelle A, Yao, Cindy Q, Liang, Bianca, Lalonde, Emilie, Haider, Syed, Simone, Nicole A, Sendorek, Dorota, Chu, Kenneth C, Moon, Nathalie C, Fox, Natalie S, Grzadkowski, Michal R, Harding, Nicholas J, Fung, Clement, Murdoch, Amanda R, Houlahan, Kathleen E, Wang, Jianxin, Garcia, David R, de Borja, Richard, Sun, Ren X, Lin, Xihui, Chen, Gregory M, Lu, Aileen, Shiah, Yu-Jia, Zia, Amin, Kearns, Ryan, and Boutros, Paul C

Subjects
Humans, Software, Simulation Training, Data Analysis, Data-visualization, Interactive plotting, Web-resources, Networking and Information Technology R&D, Biological Sciences, Information and Computing Sciences, Mathematical Sciences, Bioinformatics
Abstract

BackgroundWe introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment.ResultsThis open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines.ConclusionBPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.

Published
2019

27. Continued 5α-Reductase Inhibitor Use after Prostate Cancer Diagnosis and the Risk of Reclassification and Adverse Pathological Outcomes in the PASS.

Author

Kearns, James, Faino, Anna, Schenk, Jeanette, Newcomb, Lisa, Brooks, James, Dash, Atreya, Ellis, William, Fabrizio, Michael, Gleave, Martin, Morgan, Todd, Nelson, Peter, Thompson, Ian, Wagner, Andrew, Zheng, Yingye, Lin, Daniel, and Carroll, Peter

Subjects
5-alpha Reductase Inhibitors, Aged, Cohort Studies, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Population Surveillance, Prostate-Specific Antigen, Prostatectomy, Prostatic Neoplasms, Watchful Waiting
Abstract

PURPOSE: Outcomes in patients who enroll in active surveillance programs for prostate cancer while receiving 5α-reductase inhibitors have not been well defined. We sought to determine the association of 5α-reductase inhibitor use with the risk of reclassification in the PASS (Canary Prostate Active Surveillance Study). MATERIALS AND METHODS: Participants in the multicenter PASS were enrolled between 2008 and 2016. Study inclusion criteria were current or never 5α-reductase inhibitors use, Gleason score 3 + 4 or less prostate cancer at diagnosis, less than a 34% core involvement ratio at diagnosis and 1 or more surveillance biopsies. Included in study were 1,009 men, including 107 on 5α-reductase inhibitors and 902 who had never received 5α-reductase inhibitors. Reclassification was defined as increase in the Gleason score and/or an increase to 34% or greater in the ratio of biopsy cores positive for cancer. Adverse pathology at prostatectomy was defined as Gleason 4 + 3 or greater and/or nonorgan confined disease (pT3 or N1). RESULTS: On multivariable analysis there was no difference in reclassification between men who had received and those who had never received 5α-reductase inhibitors (HR 0.81, p = 0.31). Patients who had received 5α-reductase inhibitors were less likely to undergo radical prostatectomy (8% vs 18%, p = 0.01) or any definitive treatment (19% vs 24%, p = 0.04). In the 167 participants who underwent radical prostatectomy there was no suggestion of a difference in the rate of adverse pathology findings at prostatectomy between 5α-reductase inhibitor users and nonusers. CONCLUSIONS: Continued 5α-reductase inhibitor use after an initial diagnosis of prostate cancer was not associated with the risk of reclassification on active surveillance in men in the PASS cohort.

Published
2019

28. Refined Analysis of Prostate-specific Antigen Kinetics to Predict Prostate Cancer Active Surveillance Outcomes

Author

Cooperberg, Matthew R, Brooks, James D, Faino, Anna V, Newcomb, Lisa F, Kearns, James T, Carroll, Peter R, Dash, Atreya, Etzioni, Ruth, Fabrizio, Michael D, Gleave, Martin E, Morgan, Todd M, Nelson, Peter S, Thompson, Ian M, Wagner, Andrew A, Lin, Daniel W, and Zheng, Yingye

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Bioengineering, Prevention, Clinical Research, Aging, Prostate Cancer, Urologic Diseases, Aged, Biopsy, Clinical Decision-Making, Decision Support Techniques, Disease Progression, Humans, Kallikreins, Kinetics, Male, Middle Aged, Neoplasm Grading, North America, Predictive Value of Tests, Prospective Studies, Prostate-Specific Antigen, Prostatic Neoplasms, Risk Assessment, Risk Factors, Tumor Burden, Watchful Waiting, Prostate-specific antigen, Prostate cancer, Active surveillance, Outcomes, Urology & Nephrology, Clinical sciences
Abstract

BackgroundFor men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial.ObjectiveTo develop prediction methods for utilizing serial PSA and evaluate frequency of collection.Design, setting, and participantsData were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels.Outcome measurements and statistical analysisThe association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models.Results and limitationsA total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 [95% confidence interval 1.2-2.1, p

Published
2018

29. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Author

Iglesias, Adriana I, Mishra, Aniket, Vitart, Veronique, Bykhovskaya, Yelena, Höhn, René, Springelkamp, Henriët, Cuellar-Partida, Gabriel, Gharahkhani, Puya, Bailey, Jessica N Cooke, Willoughby, Colin E, Li, Xiaohui, Yazar, Seyhan, Nag, Abhishek, Khawaja, Anthony P, Polašek, Ozren, Siscovick, David, Mitchell, Paul, Tham, Yih Chung, Haines, Jonathan L, Kearns, Lisa S, Hayward, Caroline, Shi, Yuan, van Leeuwen, Elisabeth M, Taylor, Kent D, Blue Mountains Eye Study—GWAS group, Bonnemaijer, Pieter, Rotter, Jerome I, Martin, Nicholas G, Zeller, Tanja, Mills, Richard A, Souzeau, Emmanuelle, Staffieri, Sandra E, Jonas, Jost B, Schmidtmann, Irene, Boutin, Thibaud, Kang, Jae H, Lucas, Sionne EM, Wong, Tien Yin, Beutel, Manfred E, Wilson, James F, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Uitterlinden, André G, Vithana, Eranga N, Foster, Paul J, Hysi, Pirro G, Hewitt, Alex W, Khor, Chiea Chuen, Pasquale, Louis R, Montgomery, Grant W, Klaver, Caroline CW, Aung, Tin, Pfeiffer, Norbert, Mackey, David A, Hammond, Christopher J, Cheng, Ching-Yu, Craig, Jamie E, Rabinowitz, Yaron S, Wiggs, Janey L, Burdon, Kathryn P, van Duijn, Cornelia M, and MacGregor, Stuart

Subjects
Blue Mountains Eye Study—GWAS group, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2, Cornea, Humans, Marfan Syndrome, Corneal Diseases, Corneal Dystrophies, Hereditary, Keratoconus, Eye Diseases, Hereditary, Glaucoma, Open-Angle, Myopia, Ehlers-Danlos Syndrome, Proteoglycans, Gene Expression, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome, Human, Asian Continental Ancestry Group, European Continental Ancestry Group, Transforming Growth Factor beta2, Genome-Wide Association Study, Loeys-Dietz Syndrome, Mendelian Randomization Analysis, Decorin, Lumican, Fibrillin-1, ADAMTS Proteins, Corneal Dystrophies, Hereditary, Eye Diseases, Glaucoma, Open-Angle, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Genome, Human
Abstract

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Published
2018

31. Role of Surveillance Biopsy with No Cancer as a Prognostic Marker for Reclassification: Results from the Canary Prostate Active Surveillance Study

Author

Kearns, James T, Faino, Anna V, Newcomb, Lisa F, Brooks, James D, Carroll, Peter R, Dash, Atreya, Ellis, William J, Fabrizio, Michael, Gleave, Martin E, Morgan, Todd M, Nelson, Peter S, Thompson, Ian M, Wagner, Andrew A, Zheng, Yingye, and Lin, Daniel W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Prevention, Urologic Diseases, Clinical Research, Aged, Asymptomatic Diseases, Biomarkers, Tumor, Biopsy, Needle, Cohort Studies, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Neoplasm Grading, Neoplasm Invasiveness, Prognosis, Proportional Hazards Models, Prostate-Specific Antigen, Prostatic Neoplasms, Retrospective Studies, Time Factors, Watchful Waiting, Active surveillance, Prostate biopsy, Prostate cancer, Urology & Nephrology, Clinical sciences
Abstract

BackgroundMany patients who are on active surveillance (AS) for prostate cancer will have surveillance prostate needle biopsies (PNBs) without any cancer evident.ObjectiveTo define the association between negative surveillance PNBs and risk of reclassification on AS.Design, setting, and participantsAll men were enrolled in the Canary Prostate Active Surveillance Study (PASS) between 2008 and 2016. Men were included if they had Gleason ≤3+4 prostate cancer and

Published
2018

32. Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents.

Author

Kearns, Cristin E, Apollonio, Dorie, and Glantz, Stanton A

Subjects
Animals, Humans, Rodentia, Rats, Neoplasms, Coronary Disease, Dietary Carbohydrates, Sucrose, Lipids, Carcinogens, Truth Disclosure, Germ-Free Life, Biomedical Research, Research Design, History, 20th Century, History, 21st Century, Publications, Hyperlipidemias, Research Support as Topic, Gastrointestinal Microbiome, Sugars, History, 20th Century, 21st Century, Complementary and Alternative Medicine, Prevention, Nutrition, Cancer, Developmental Biology, Biological Sciences, Medical and Health Sciences, Agricultural and Veterinary Sciences
Abstract

In 1965, the Sugar Research Foundation (SRF) secretly funded a review in the New England Journal of Medicine that discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease (CHD). SRF subsequently funded animal research to evaluate sucrose's CHD risks. The objective of this study was to examine the planning, funding, and internal evaluation of an SRF-funded research project titled "Project 259: Dietary Carbohydrate and Blood Lipids in Germ-Free Rats," led by Dr. W.F.R. Pover at the University of Birmingham, Birmingham, United Kingdom, between 1967 and 1971. A narrative case study method was used to assess SRF Project 259 from 1967 to 1971 based on sugar industry internal documents. Project 259 found a statistically significant decrease in serum triglycerides in germ-free rats fed a high sugar diet compared to conventional rats fed a basic PRM diet (a pelleted diet containing cereal meals, soybean meals, whitefish meal, and dried yeast, fortified with a balanced vitamin supplement and trace element mixture). The results suggested to SRF that gut microbiota have a causal role in carbohydrate-induced hypertriglyceridemia. A study comparing conventional rats fed a high-sugar diet to those fed a high-starch diet suggested that sucrose consumption might be associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans. SRF terminated Project 259 without publishing the results. The sugar industry did not disclose evidence of harm from animal studies that would have (1) strengthened the case that the CHD risk of sucrose is greater than starch and (2) caused sucrose to be scrutinized as a potential carcinogen. The influence of the gut microbiota in the differential effects of sucrose and starch on blood lipids, as well as the influence of carbohydrate quality on beta-glucuronidase and cancer activity, deserve further scrutiny.

Published
2017

33. Do Sugar-Sweetened Beverages Cause Obesity and Diabetes? Industry and the Manufacture of Scientific Controversy.

Author

Schillinger, Dean, Tran, Jessica, Mangurian, Christina, and Kearns, Cristin

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Metabolic and endocrine, Beverages, Conflict of Interest, Diabetes Mellitus, Dietary Sucrose, Food Industry, Humans, Obesity, Research Support as Topic, Sweetening Agents, Clinical Sciences, Public Health and Health Services
Abstract

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.

Published
2016

34. Sugar Industry and Coronary Heart Disease Research: A Historical Analysis of Internal Industry Documents

Author

Kearns, Cristin E, Schmidt, Laura A, and Glantz, Stanton A

Subjects
Nutrition, Heart Disease - Coronary Heart Disease, Cardiovascular, Prevention, Heart Disease, Biomedical Research, Coronary Disease, Evidence-Based Medicine, Food Industry, History, 20th Century, History, 21st Century, Humans, Sucrose, Sweetening Agents, United States, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services
Abstract

Early warning signals of the coronary heart disease (CHD) risk of sugar (sucrose) emerged in the 1950s. We examined Sugar Research Foundation (SRF) internal documents, historical reports, and statements relevant to early debates about the dietary causes of CHD and assembled findings chronologically into a narrative case study. The SRF sponsored its first CHD research project in 1965, a literature review published in the New England Journal of Medicine, which singled out fat and cholesterol as the dietary causes of CHD and downplayed evidence that sucrose consumption was also a risk factor. The SRF set the review's objective, contributed articles for inclusion, and received drafts. The SRF's funding and role was not disclosed. Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD. Policymaking committees should consider giving less weight to food industry-funded studies and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.

Published
2016

35. Rounds Today: A Qualitative Study of Internal Medicine and Pediatrics Resident Perceptions

Author

Rabinowitz, Raphael, Farnan, Jeanne, Hulland, Oliver, Kearns, Lisa, Long, Michele, Monash, Bradley, Bhansali, Priti, and Fromme, H Barrett

Subjects
Curriculum and Pedagogy, Education, Health Services, Clinical Research, Behavioral and Social Science, Patient Safety, Quality Education, Good Health and Well Being, Adult, Attitude of Health Personnel, Family, Female, Focus Groups, Hospitals, Teaching, Humans, Internal Medicine, Internship and Residency, Male, Patient Care, Patient Participation, Pediatrics, Perception, Teaching Rounds, Curriculum and pedagogy
Abstract

BackgroundAttending rounds is a key component of patient care and education at teaching hospitals, yet there is an absence of studies addressing trainees' perceptions of rounds.ObjectiveTo determine perceptions of pediatrics and internal medicine residents about the current and ideal purposes of inpatient rounds on hospitalist services.MethodsIn this multi-institutional qualitative study, the authors conducted focus groups with a purposive sample of internal medicine and pediatrics residents at 4 teaching hospitals. The constant comparative method was used to identify themes and codes.ResultsThe study identified 4 themes: patient care, clinical education, patient/family involvement, and evaluation. Patient care included references to activities on rounds that forwarded care of the patient. Clinical education pertained to teaching/learning on rounds. Patient/family involvement encompassed comments about incorporating patients and families on rounds. Evaluation described residents demonstrating skill for attendings.ConclusionsResident perceptions of the purposes of rounds aligned with rounding activities described by prior observational studies of rounds. The influence of time pressures and the divergent needs of participants on today's rounds placed these identified purposes in tension, and led to resident dissatisfaction in the achievement of all of them. Suboptimal congruency exists between perceived resident clinical education and specialty-specific milestones. These findings suggest a need for education of multiple stakeholders by (1) enhancing faculty teaching strategies to maximize clinical education while minimizing inefficiencies; (2) informing residents about the value of patient interactions and family-centered rounds; and (3) educating program directors in proper alignment of inpatient rotational objectives to the milestones.

Published
2016

36. Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients

Author

Kilburn, Jeremy M, Soike, Michael H, Lucas, John T, Ayala-Peacock, Diandra, Blackstock, William, Isom, Scott, Kearns, William T, Hinson, William H, Miller, Antonius A, Petty, William J, Munley, Michael T, and Urbanic, James J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Biomedical Imaging, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Aged, Aged, 80 and over, Cohort Studies, Disease-Free Survival, Female, Humans, Lung Neoplasms, Male, Middle Aged, Radiotherapy, Image-Guided, Retrospective Studies, Treatment Outcome, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeImage guided radiation therapy (IGRT) is designed to ensure accurate and precise targeting, but whether improved clinical outcomes result is unknown.Methods and materialsA retrospective comparison of locally advanced lung cancer patients treated with and without IGRT from 2001 to 2012 was conducted. Median local failure-free survival (LFFS), regional, locoregional failure-free survival (LRFFS), distant failure-free survival, progression-free survival, and overall survival (OS) were estimated. Univariate and multivariate models assessed the association between patient- and treatment-related covariates and local failure.ResultsA total of 169 patients were treated with definitive radiation therapy and concurrent chemotherapy with a median follow-up of 48 months in the IGRT cohort and 96 months in the non-IGRT cohort. IGRT was used in 36% (62 patients) of patients. OS was similar between cohorts (2-year OS, 47% vs 49%, P = .63). The IGRT cohort had improved 2-year LFFS (80% vs 64%, P = .013) and LRFFS (75% and 62%, P = .04). Univariate analysis revealed IGRT and treatment year improved LFFS, whereas group stage, dose, and positron emission tomography/computed tomography planning had no impact. IGRT remained significant in the multivariate model with an adjusted hazard ratio of 0.40 (P = .01). Distant failure-free survival (58% vs 59%, P = .67) did not differ significantly.ConclusionIGRT with daily cone beam computed tomography confers an improvement in the therapeutic ratio relative to patients treated without this technology.

Published
2016

37. Reirradiation for second primary or recurrent cancers of the head and neck: Dosimetric and outcome analysis

Author

Garg, Shivank, Kilburn, Jeremy M, Lucas, John T, Randolph, David, Urbanic, James J, Hinson, William H, Kearns, William T, Porosnicu, Mercedes, and Greven, Kathryn

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Dental/Oral and Craniofacial Disease, Cancer, Rare Diseases, Clinical Research, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Head and Neck Neoplasms, Humans, Middle Aged, Neoplasm Recurrence, Local, Neoplasms, Second Primary, Radiotherapy Dosage, Re-Irradiation, Retrospective Studies, head and neck, reirradiation, carotid arteries, blowout, dosimetry, Dentistry, Otorhinolaryngology, Clinical sciences
Abstract

BackgroundThe purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers.MethodsFifty patients underwent ≥2 courses of radiation therapy (RT) postoperatively or definitively with or without chemotherapy. Composite dose volume histograms (DVHs) for selected anatomic structures were correlated with grade ≥3 late toxicity.ResultsMedian initial and retreatment radiation dose was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%, respectively, with 13 months median follow-up. Thirty-four percent of patients experienced grade ≥3 late toxicity with 1 death from carotid blowout. The DVH corresponding to the carotid blowout fell above the third quartile compared with other patients.ConclusionOur analysis is the first to systematically evaluate the dose to the carotid artery using composite dosimetry in head and neck reirradiation patients, and demonstrates a promising technique for evaluating the dose to other normal tissue structures. © 2015 Wiley Periodicals, Inc. Head Neck 38: E961-E969, 2016.

Published
2016

38. The Causal Role of IL-4 and IL-13 in Schistosoma mansoni Pulmonary Hypertension

Author

Kumar, Rahul, Mickael, Claudia, Chabon, Jacob, Gebreab, Liya, Rutebemberwa, Alleluiah, Garcia, Alexandra Rodriguez, Koyanagi, Daniel E, Sanders, Linda, Gandjeva, Aneta, Kearns, Mark T, Barthel, Lea, Janssen, William J, Mauad, Thais, Bandeira, Angela, Schmidt, Eric, Tuder, Rubin M, and Graham, Brian B

Subjects
Vector-Borne Diseases, Digestive Diseases, Lung, Rare Diseases, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Cardiovascular, Good Health and Well Being, Animals, Bone Marrow Transplantation, Cell Adhesion Molecules, Humans, Hypertension, Pulmonary, Inflammation, Intercellular Signaling Peptides and Proteins, Interleukin-13, Interleukin-4, Interleukin-4 Receptor alpha Subunit, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, STAT6 Transcription Factor, Schistosoma mansoni, Schistosomiasis mansoni, Smad2 Protein, Smad3 Protein, Th1 Cells, Th17 Cells, Transforming Growth Factor beta, Vascular Remodeling, pulmonary hypertension, schistosomiasis, Th2 cells, transforming growth factor-beta, transforming growth factor-β, Medical and Health Sciences, Respiratory System
Abstract

RationaleThe etiology of schistosomiasis-associated pulmonary arterial hypertension (PAH), a major cause of PAH worldwide, is poorly understood. Schistosoma mansoni exposure results in prototypical type-2 inflammation. Furthermore, transforming growth factor (TGF)-β signaling is required for experimental pulmonary hypertension (PH) caused by Schistosoma exposure.ObjectivesWe hypothesized type-2 inflammation driven by IL-4 and IL-13 is necessary for Schistosoma-induced TGF-β-dependent vascular remodeling.MethodsWild-type, IL-4(-/-), IL-13(-/-), and IL-4(-/-)IL-13(-/-) mice (C57BL6/J background) were intraperitoneally sensitized and intravenously challenged with S. mansoni eggs to induce experimental PH. Right ventricular catheterization was then performed, followed by quantitative analysis of the lung tissue. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH was also systematically analyzed.Measurements and main resultsMice with experimental Schistosoma-induced PH had evidence of increased IL-4 and IL-13 signaling. IL-4(-/-)IL-13(-/-) mice, but not single knockout IL-4(-/-) or IL-13(-/-) mice, were protected from Schistosoma-induced PH, with decreased right ventricular pressures, pulmonary vascular remodeling, and right ventricular hypertrophy. IL-4(-/-)IL-13(-/-) mice had less pulmonary vascular phospho-signal transducer and activator of transcription 6 (STAT6) and phospho-Smad2/3 activity, potentially caused by decreased TGF-β activation by macrophages. In vivo treatment with a STAT6 inhibitor and IL-4(-/-)IL-13(-/-) bone marrow transplantation also protected against Schistosoma-PH. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH had evidence of type-2 inflammation.ConclusionsCombined IL-4 and IL-13 deficiency is required for protection against TGF-β-induced pulmonary vascular disease after Schistosoma exposure, and targeted inhibition of this pathway is a potential novel therapeutic approach for patients with schistosomiasis-associated PAH.

Published
2015

39. Sugar industry influence on the scientific agenda of the National Institute of Dental Research's 1971 National Caries Program: a historical analysis of internal documents.

Author

Kearns, Cristin E, Glantz, Stanton A, and Schmidt, Laura A

Subjects
Humans, Dental Caries, Dietary Sucrose, Dental Research, Public Health, Science, Nutrition Policy, Food Industry, Conflict of Interest, Scientific Misconduct, History, 20th Century, Documentation, Academies and Institutes, United States, History, 20th Century, Infectious Diseases, Dental/Oral and Craniofacial Disease, Oral and Gastrointestinal, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundIn 1966, the National Institute of Dental Research (NIDR) began planning a targeted research program to identify interventions for widespread application to eradicate dental caries (tooth decay) within a decade. In 1971, the NIDR launched the National Caries Program (NCP). The objective of this paper is to explore the sugar industry's interaction with the NIDR to alter the research priorities of the NIDR NCP.Methods and findingsWe used internal cane and beet sugar industry documents from 1959 to 1971 to analyze industry actions related to setting research priorities for the NCP. The sugar industry could not deny the role of sucrose in dental caries given the scientific evidence. They therefore adopted a strategy to deflect attention to public health interventions that would reduce the harms of sugar consumption rather than restricting intake. Industry tactics included the following: funding research in collaboration with allied food industries on enzymes to break up dental plaque and a vaccine against tooth decay with questionable potential for widespread application, cultivation of relationships with the NIDR leadership, consulting of members on an NIDR expert panel, and submission of a report to the NIDR that became the foundation of the first request for proposals issued for the NCP. Seventy-eight percent of the sugar industry submission was incorporated into the NIDR's call for research applications. Research that could have been harmful to sugar industry interests was omitted from priorities identified at the launch of the NCP. Limitations are that this analysis relies on one source of sugar industry documents and that we could not interview key actors.ConclusionsThe NCP was a missed opportunity to develop a scientific understanding of how to restrict sugar consumption to prevent tooth decay. A key factor was the alignment of research agendas between the NIDR and the sugar industry. This historical example illustrates how industry protects itself from potentially damaging research, which can inform policy makers today. Industry opposition to current policy proposals-including a World Health Organization guideline on sugars proposed in 2014 and changes to the nutrition facts panel on packaged food in the US proposed in 2014 by the US Food and Drug Administration-should be carefully scrutinized to ensure that industry interests do not supersede public health goals.

Published
2015

40. Meta‐analysis of Genome‐Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

Author

Springelkamp, Henriët, Mishra, Aniket, Hysi, Pirro G, Gharahkhani, Puya, Höhn, René, Khor, Chiea‐Chuen, Bailey, Jessica N Cooke, Luo, Xiaoyan, Ramdas, Wishal D, Vithana, Eranga, Koh, Victor, Yazar, Seyhan, Xu, Liang, Forward, Hannah, Kearns, Lisa S, Amin, Najaf, Iglesias, Adriana I, Sim, Kar‐Seng, Leeuwen, Elisabeth M, Demirkan, Ayse, der Lee, Sven, Loon, Seng‐Chee, Rivadeneira, Fernando, Nag, Abhishek, Sanfilippo, Paul G, Schillert, Arne, de Jong, Paulus TVM, Oostra, Ben A, Uitterlinden, André G, Hofman, Albert, Consortium, NEIGHBORHOOD, Zhou, Tiger, Burdon, Kathryn P, Spector, Timothy D, Lackner, Karl J, Saw, Seang‐Mei, Vingerling, Johannes R, Teo, Yik‐Ying, Pasquale, Louis R, Wolfs, Roger CW, Lemij, Hans G, Tai, E‐Shyong, Jonas, Jost B, Cheng, Ching‐Yu, Aung, Tin, Jansonius, Nomdo M, Klaver, Caroline CW, Craig, Jamie E, Young, Terri L, Haines, Jonathan L, MacGregor, Stuart, Mackey, David A, Pfeiffer, Norbert, Wong, Tien‐Yin, Wiggs, Janey L, Hewitt, Alex W, Duijn, Cornelia M, and Hammond, Christopher J

Subjects
Aging, Human Genome, Eye Disease and Disorders of Vision, Genetics, Neurosciences, Neurodegenerative, Eye, Asian People, Genome-Wide Association Study, Glaucoma, Humans, Optic Disk, Optic Nerve Diseases, Quantitative Trait Loci, White People, NEIGHBORHOOD Consortium, GWAS, cup area, disc area, glaucoma, Public Health and Health Services, Epidemiology
Abstract

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

Published
2015

41. Rhesus monkeys and baboons develop clotting factor VIII inhibitors in response to porcine endothelial cells or islets

Author

Stewart, John M, Tarantal, Alice F, Hawthorne, Wayne J, Salvaris, Evelyn J, O'Connell, Philip J, Nottle, Mark B, d'Apice, Anthony JF, Cowan, Peter J, and Kearns‐Jonker, Mary

Subjects
Biomedical and Clinical Sciences, Immunology, Biotechnology, Hematology, Transplantation, Organ Transplantation, Amino Acid Sequence, Animals, Animals, Genetically Modified, Antibodies, Heterophile, Computer Simulation, Endothelial Cells, Factor VIII, Galactosyltransferases, Gene Knockout Techniques, Humans, Islets of Langerhans Transplantation, Macaca mulatta, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Papio, Protein Interaction Domains and Motifs, Recombinant Proteins, Sequence Homology, Amino Acid, Sus scrofa, Transplantation, Heterologous, clotting factor VIII, clotting factor VIII inhibitor, non-human primate, porcine, xenoantibody, Clinical Sciences, Surgery, Clinical sciences
Abstract

BackgroundXenotransplantation of porcine organs holds promise of solving the human organ donor shortage. The use of α-1,3-galactosyltransferase knockout (GTKO) pig donors mitigates hyperacute rejection, while delayed rejection is currently precipitated by potent immune and hemostatic complications. Previous analysis by our laboratory suggests that clotting factor VIII (FVIII) inhibitors might be elicited by the structurally restricted xenoantibody response which occurs after transplantation of either pig GTKO/hCD55/hCD59/hHT transgenic neonatal islet cell clusters or GTKO endothelial cells.MethodsA recombinant xenoantibody was generated using sequences from baboons demonstrating an active xenoantibody response at day 28 after GTKO/hCD55/hCD59/hHT transgenic pig neonatal islet cell cluster transplantation. Rhesus monkeys were immunized with GTKO pig endothelial cells to stimulate an anti-non-Gal xenoantibody response. Serum was collected at days 0 and 7 after immunization. A two-stage chromogenic assay was used to measure FVIII cofactor activity and identify antibodies which inhibit FVIII function. Molecular modeling and molecular dynamics simulations were used to predict antibody structure and the residues which contribute to antibody-FVIII interactions. Competition ELISA was used to verify predictions at the domain structural level.ResultsAntibodies that inhibit recombinant human FVIII function are elicited after non-human primates are transplanted with either GTKO pig neonatal islet cell clusters or endothelial cells. There is an apparent increase in inhibitor titer by 15 Bethesda units (Bu) after transplant, where an increase greater than 5 Bu can indicate pathology in humans. Furthermore, competition ELISA verifies the computer modeled prediction that the recombinant xenoantibody, H66K12, binds the C1 domain of FVIII.ConclusionsThe development of FVIII inhibitors is a novel illustration of the potential impact the humoral immune response can have on coagulative dysfunction in xenotransplantation. However, the contribution of these antibodies to rejection pathology requires further evaluation because "normal" coagulation parameters after successful xenotransplantation are not fully understood.

Published
2014

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

Author

Obbina Abani, Ali Abbas, Fatima Abbas, Joshua Abbas, Kasim Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Alison Abbott, Nabeel Abdallah, Ammar Abdelaziz, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Audrey Abdul, Basir Abdul, Siddiqui Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Abeer Ul Amna, Lynn Abel, Katrina Abernethy, Movin Abeywickrema, Chandra Abhinaya, Affyarsyah Abidin, Adebanke Aboaba, Abigail Aboagye-Odei, Christopher Aboah, Heba Aboelela, Hani Abo-Leyah, Karim Abouelela, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Ahmed Abousamra, Mona Abouzaid, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Rebecca Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yousuf Abusamra, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Faustina Acheampong, Prince Acheampong, Sarah Acheampong, Janet Acheson, Shiella Achieng, Andres Acosta, Rebecca Acquah, Catherine Acton, Jacqueline Adabie-Ankrah, Paul Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Marta Adamczyk, Carol Adams, Charlotte Adams, Daniel Adams, Kate Adams, Laura Adams, Nikkita Adams, Richard Adams, Tim Adams, Laura Adamu-Ikeme, Krishma Adatia, Kirsty Adcock, Lawrence Addai-Boampong, Afua Addo, Oluwatobi Adeagbo, Ade Adebiyi, Ogunlana Adedeji, Yewande Adegeye, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Femi W Adeoye, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Adedamola Adeyanju, Joyce Adeyemi, Tenifayo Adeyemo, Binay Adhikari, Shanti A Adhikari, Rina Adhikary, Adhikarla Aditya, Patience Adjepong, Gabrielle Adkins, Adnan Adnan, Marguerite Adriaanse, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Patricia Afrim, Felicia Akua Afriyie, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Laura Aguilar Jimenez, Jacqueline Afrakomah Agyekum, Kwame Agyen, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Afshan Ahmed, Ashar Ahmed, Asim Ahmed, Basheer A R Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Hanad Ahmed, Irshad Ahmed, Khaled Ahmed, Khalil Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rawya Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sana G Ahmed, Syed Ahmed, Syed H Ahmed, Roa Ahmed Ali, Bilal Ahmed Mohamud, Sana Ahmed, Sana Ahmer, Augustine Ahonia, Christine Aiken, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Bolutito Akinbiyi, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Mohammad Akram, Olugbenro Aktinade, Uzayr Akudi, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Adegoke Alabi, Narendra Aladangady, Mohamed Alafifi, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Albertus Albertus, Lorraine Albon, Angela Alcala, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Abdullah Aldesouki, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ram Maya Ale, Ana Alegria, Alison Alexander, Courtney Alexander, John Alexander, Peter D G Alexander, Julyan Al-fori, Laith Alghazawi, Osama Alhabsha, Bahij Al-Hakim, Rafil Alhameed, Mohammed Al-Hayali, Shams Al-Hity, Ali Ali, Amanda Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohamed Ali, Mohammad Ali, Muhammad S Ali, Nayab Ali, Oudai Ali, Ramla Ali, Sakina Ali, Syed Ali, Emilio Aliberti, Jade Alin, Abid Alina, Analyn Alipustain, Bachti Alisjahbana, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Abdullah Alkhudhayri, Moutaz Alkhusheh, Fiona Allan, Nataliya Allan, Alison Allanson, Robert Allcock, Eireann Allen, Jade Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Tania Allen, Abiola Alli, Kathryn Allison, Bethan Allman, Helen K Allsop, Lynne Allsop, David Allsup, Amal F T Almahroos, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Riyam Al-Sammarraie, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Fadia Alsheikh, Bashar Al-Sheklly, Sara Altaf, Amanda Alty, Mary Alvarez, Maria Alvarez Corral, Edward Alveyn, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Amel Amelia Ganefianty, Katharine Ames, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Badshah Amit, Amjad Amjad, Neelma Amjad, James Amoah-Dankwa, Victoria Amosun, Muhammad Amsal, Khaled Amsha, John Amuasi, Noelia Amutio Martin, Pugh Amy, Ann Anada, Atul Anand, Samantha Anandappa, Satya D Anantapatnaikuni, Ellen Anderson, Julie Anderson, Laura Anderson, Marina Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rebecca Anderson, Rory Anderson, Samantha Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Joyann Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Maldwyn Ansah, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Elena Apetri, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia F Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Samuel Archer, Simon Archer, Daniele Arcoria, Christian Ardley, Ana-Maria Arias, Oluwatoyin Aribike, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Jennifer Armistead, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Wendy Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Andrew Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Armena Arumaithurai, Ayush Arya, Rita Arya, Diptesh Aryal, Denisa Asandei, Adeeba Asghar, Malik Asghar, Arif Ashab, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Zakariya Ashfak, Ayesha Ashfaq, Abdul Ashish, Dawn Ashley, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Fiona J Ashworth, Rebecca Ashworth, Arshia Aslam, I Aslam, Suhail Aslam, Laura Aslett, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Abolaji Atomode, Brygitta Atraskiewicz, Abdul A Attia, Eva Attubato, Marie Attwood, Paula Aubrey, Zoltan Auer, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Hnin Wint Wint Aung, Ko Ko Aung, Kyaw Thu Aung, Nwe Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Malcolm Avari, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Abuzar Awadelkareem, Gabriel Awadzi, Mahmoud Awaly, Atia Awan, Aszad Aya, Eman Ayaz, John Maximilian Ayerh, Amanda Ayers, Jawwad Azam, Ahmed Azeem, Mohammed Azharuddin, Ammar Aziz, Ghazala Aziz, Imran Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Michel-Elie Bachour, Alisjahbana Bachti, Gina Bacon, Jenny Bacon, Bibi Badal, Aysha Badat, Maryuma Bader, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, Angela Bailey, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Lucy Bailey, Maria A Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Eilidh Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Danielle C Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Mark Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Ameet Bakhai, Nauman Bakhtiar, Panos Bakoulas, Dhanalakshmi Bakthavatsalam, Niranjan Balachandran, Andrea Balan, Prasath Balasingam, Theodosios Balaskas, Madhu Balasubramaniam, Nicola Balatoni, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Fiona Baldwin, Rebekah Baldwin-Jones, Nichola Bale, James Balfour, Matthew Ball, Robert Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Abeir Baltmr, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Santosh Baniya, Omar Bani-Saad, Harrison Banks, Luke Banks, Paul Banks, Claudia Bann, Helen Bannister, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Sharad Chandra Baral, Desislava Baramova, Russel Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Amanda Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Erandi Barker, Helen Barker, Joseph Barker, Leon Barker, Lesley Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Rory Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, Prince Gyenti Barning, William Barnsley, Andrew Barr, David Barr, James Barr, Charlotte Barr, Nina Barratt, Shaney 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Patrick Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Alison Eccles, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Mary Edmondson, Tracy Edmunds, Abby Edwards, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Martin Edwards, Sophie Edwards, Jenny Eedle, Aline Eggink, Dawn Egginton, Sam Eggleston, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Nagla Elashhar, Lisa Elawamy, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Emma Eldridge, Diana Eleanor, Uchenna Elenwa, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Mohamed A A Elhadi, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura N Ellerton, Lucy Elliot, Amy Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Sian Elliott, Annie Ellis, Christine Ellis, Kaytie Ellis, Leila Ellis, Rupert Ellis, Tak-Yan Ellis, Yvette Ellis, Alison C Ellwood, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed El-Naggar, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Mohammed A S A Elsayed, Sally El-Sayeh, Hana El-Sbahi, Mohammad Elsebaei, Tarek Elsefi, Karim El-Shakankery, Alguili Elsheikh, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Anna Emery, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Dickson Enenche, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Peter Eskander, Hanif Esmail, Fatheha Essa, Brynach Evans, Chris Evans, Debra Evans, E Evans, Emrys Evans, Gail Evans, Gareth Evans, Isabel Evans, Jack Evans, Jacqueline Evans, Jennifer Evans, John Evans, Jolanta Evans, Lisa Evans, Lynn Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Sharon Evans, Sian Evans, Teriann Evans, Tomos Evans, Caroline Everden, Serenydd Everden, Lynette Every, Hayley Evison, Lynsey Evison, Chiamaka Ezenduka, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Ian Fairbairn, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Ayaan Farah, Muna Farah, Qayyum Farah, Nowin Z Fard, Leila Fares, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Holly Farr, Aaron Farrell, Barbara Farrell, Fayed Farrukh, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Suman Fathima, Nibah Fatimah, Maria Faulkner, Saul N Faust, Clair Favager, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Aisthath Fazleen, Simon Fearby, Connie Fearnley, Alex Feben, Federico Fedel, Daria Fedorova, Christopher Fegan, Mae Felongo, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Ruth Fennelly, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Gloria Ferenando, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Jaime Fernandez Roman, Callum J Fernando, Jessica Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Sheldon Ferron, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Santos Filipa, Sarah A Filson, Shona Finan, Sarah Finbow, Deborah J Finch, Joanne Finch, Laurie Finch, Simon Finch, Spencer Finch, Natalie Fineman, Jim Finlayson, Lauren Finlayson, Adam Finn, Joanne Finn, Dylan Finnerty, Clare Finney, Deborah Finucane, Sofia Fiouni, Jo Fiquet, Promise Firi, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Carolyn Fitton, Felicity Fitzgerald, Fiona Fitzgerald, Karen Fitzjohn, Jan Flaherty, Michael Flanagan, Charles Flanders, Nikolaos Flaris, Gail Fleming, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Anna Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Fiona Flett, Karen Flewitt, Sarah Flockhart, Christopher Flood, Ian Floodgate, Jonathan Flor, Vincent Florence, Mary Flowerdew, Sharon Floyd, Margaret J Flynn, Rachel Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Paul Foley, Linda Folkes, Tracey Fong, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Helen R Foot, Jayne Foot, Jane Forbes, Amber Ford, Jamie Ford, Imogen Fordham, Jennifer Foreman, Matthew Forester, Mohammad Forkan, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Abigail Forsyth, Julian Forton, Conrad Foster, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Natasha Fowkes, Emily Fowler, Robert Fowler, Stephen Fowler, Amy Fox, Claire Fox, Heather Fox, Jonathan Fox, Laura Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Eva Fraile, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Siobhan Franklin, Catherine Fraser, Andi Fratila, Sharon Frayling, Martyn Fredlund, Anna Freeman, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Thomas French, Karen Freshwater, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Andrzej Frygier, Bridget Fuller, Liz Fuller, Lucy Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Zoë Gabriel, Hadiza Gachi, Sophie Gaffarena, Sarah Gage, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Babita Gajmer, Zacharoula Galani, Christopher Gale, Hugo Gale, Linda Gale, Rebecca Gale, Swetha Gali, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Feroze Gallam, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Anna Galvin, Victoria Galvis, Gareth Gamble, Laura Gamble, Liz Gamble, Brian Gammon, Chien N Gan, Muhammad B Ganaie, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Thenugan Ganeshanathan, Saibal Ganguly, Abrar Gani, Pauline Ganley, Ukraina Garcia, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Louis Gardner, Mark Garfield, Atul Garg, Isha Garg, Nathan Garlick, Daniel Garner, Justin Garner, Lucie Garner, Zoe Garner, Rosaline Garr, Kathryn A Garrero, Manisha Gartaula, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Sophie Gayle, Catherine Geddie, Ian Gedge, Sarah Gee, Fartuun Geele, Kalaichelvi Geerthan, Minnie Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Neal Gent, Susan Gent, Natalie Geoghegan, Aparna George, Bini George, Sam George, Susan George, Tina George, Valerie P George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Siobhan Gettings, Hisham Ghanayem, Bijan Ghavami Kia, Shaista Ghazal, Anca Gherman, Alison Ghosh, Dipansu Ghosh, Justin Ghosh, Subhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Chris Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Jamie Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Mary Gigi, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, James Gilham, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Lesley Gilmour, Louis Ginn, Franciscus Ginting, Theodora Giokanini-Royal, Anna Gipson, Barbie Giri, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Eleanor Glenday, Ana Glennon, Jodie Glossop, John Glover, Kyle Glover, Michelle Glover, Jan Glover Bengtsson, Deborah Glowski, Sharon Glynn, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Sarah Godlee, Emma Godson, Gillian Godwin, Sukanya Gogoi, Aiky Goh, Manjinder Gohel, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Vicky Goodall, Bob Goodenough, Anna Goodfellow, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Chris Gordon, Sally Gordon, Robin Gore, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Maria Gorniok, Diana Gorog, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Nicole Gould, Susan Gould, Charlotte Goumalatsou, Lysander Gourbault, Abha Govind, Rajesh Govindan, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Cheryl Graham, Clive Graham, Jonathan Graham, Justin Graham, Libby Graham, Rachel Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Kirstie Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Glaxy Gray, Jackie Gray, Karen Gray, Nicola Gray, Roxanne Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Amy Green, Amy S Green, Charlotte Green, Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Jack Grenville, Jo Gresty, Susan Grevatt, Glaxy Grey, Samuel Gribben, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sandra Griffiths, Sarah Griffiths, Scott Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Evelina Grobovaite, Dorothy Grogono, Clarissa Grondin, Rachel Groome, Pauline Grose, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Jacinta Guerin, Sharazeq Guettari, Shivang Gulati, Vikas Gulia, Harsha Gunasekara, Pumali Gunasekera, Malin Gunawardena, Kirun Gunganah, Jessica Gunn, Emma Gunter, Anup Kumar Gupta, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Rishi Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Victoria Guratsky, Alvyda Gureviciute, Sambasivarao Gurram, Anju Gurung, Bhawana Gurung, Lilly Gurung, Shraddha Gurung, Sabi Gurung Rai, Hazel Guth, Nick Guthrine, Pradip Gyanwali, Sushma Gyawali, Nam Xuan Ha, Nguyen Thanh Ha, Ruth Habibi, Berkin Hack, James Hackett, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Nicholas Hadfield, Sally Hadfield, Michalis Hadjiandreou, Nikolaos Hadjisavvas, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Javed Hafsa, Samantha Hagan, Jack W Hague, Rosemary Hague, Nafeesah Haider, Kate Haigh, Victoria Haile, Jessica Hailstone, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Danielle Hake, Lukman Hakeem, Anne Haldeos, Writaja Halder, Emily Hale, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alaina Halim, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Laura Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Jackie Halliday, Akmal Hallman, Heather Halls, Maryam Hamdollah-Zadeh, Ifedadepo A Hamed-Adekale, Bilal Hameed, Mohammed Hameed, Raph L Hamers, Imran Hamid, Mohamad Hamie, Raymond Hamill, Bethany Hamilton, Fergus Hamilton, Gus Hamilton, Leigh Hamilton, Melanie Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Emily Hammond, Leah Hammond, Sally Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, James A Hampson, Jude Hampson, Lucy Hampson, Lisa Hamzah, Jenny Han, Ozan Hanci, Sadiyah Hand, Lala Handayani, Jasmine Handford, Soran Handrean, Nina K Handzewniak, Sarah Haney, Vu Thi Kim Hang, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Helena Hanratty, Daniel Hansen, Anita Hanson, Ashley Hanson, Helen Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Ala Haqiqi, Monjurul Haque, Henry Harcourt, Lesley Harden, Zoe Harding, Simon Hardman, Marc Hardwick, Gareth Hardy, Joanna Hardy, Yasmine Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, James Hargraves, Carolyn Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Heather Harper, James Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Kate Harrington, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, Sophie Harris, David Harrison, Laura Harrison, Melanie Harrison, Olakunbi A Harrison, Rachael Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Jessica Hartley, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Alice Harvey, Angela Harvey, Anna Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Zoe Harzeli, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Jack Haslam, Zena Haslam, Grace Hasnip, Adil Hassan, Ali Hassan, Amro Hassan, Awab Hassan, Zeinab Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Sarah Hathaway-Lees, Jonathan Hatton, Jennifer Hau, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Lydia Hawker, Annie Hawkins, Joe Hawkins, Nancy Hawkins, W John Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Alasdair W Hay, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Carole Hays, Sarah Haysom, James Hayward, Patrick Haywood, Hazel Haywood Hasford, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Jessica L Healy, Amy Hearn, David Heasman, Angela Heath, Debbie Heath, Rowan Heath, Diane Heaton, Adam Heavens, Kerry Hebbron, Catherine Heckman, Gemma Hector, Sadie Heddon, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Richard Heinink, Rajdeep Heire, Ingvild Helgesen, Joanne Hemingway, Ulla Hemmila, Beth Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Eilidh Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Lucas E Hermans, Fe Marie Hernandez, Emma Heron, Lisa Heron, William Herrington, Emilia Heselden, Peta Heslop, Tracey Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Nicola Hewitson, Claire Hewitt, Davina Hewitt, Richard Hewitt, Samuel Hey, Robert S Heyderman, Mathis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, John Hickey, Naomi Hickey, Peter Hickey, Nicky Hickman, Alex Hicks, Jenny Hicks, Scott R Hicks, Phan Thi Thu Hien, Daniel Higbee, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Lisa Hill, Lucy Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Catherine Hillman-Cooper, Jon Hilton, Zoe Hilton, Sarah Hinch, Andrew Hindle, Esther Hindley, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Claire Hirst, Lindsay Hirst, Jemma Hives, Htet M Hlaing, Benson Ho, David K K Ho, Rosemary Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Christopher Hodge, Simon Hodge, Lesley Hodgen, George Hodgetts, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Mike Hodson, Alison Hogan, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Catherine Holbrook, Rebecca Holbrook, Catherine Holden, Jill Holden, Melinda Holden, Sophie Holden, Thomas Holder, Niels Holdhof, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Poppy Holland, Susan Holland, Marie L Hollands, Elizabeth Holliday, Kyra Holliday, Mark Holliday, Nina Holling, Laszlo Hollos, Nora Hollos, Leah Holloway, Simon Holloway, Max Hollowday, Marcus Hollyer, Amy Holman, Ann Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Beth Holroyd-Hind, Lyndsey Holt, Siobhan Holt, Susie Holt, Alexandra Holyome, Marie Home, Renate Homewood, Kate Hong, Louise Hoole, Clare Hooper, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Thomas Horne, Zoey Horne, Rebecca Horner, Caroline Horrobin, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Catherine Houghton, Kathryn Houghton, Rebecca Houlihan, Kay Housely, Hamish Houston, Roseanna Hovvels, Lee How, Laura Howaniec, Joanne Howard, Kate Howard, Laura Howard, Linda Howard, Lucy Howard, Megan Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Louise Howard-Sandy, Serena Howe, Alice Howell, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Ruth Howman, Josh Hrycaiczuk, Hein Htet, Naing Z Htoon, Su Htwe, Ying Hu, Chiang O H Huah, Sylvia Huang, Kelly Hubbard, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Suzanne Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Caitlin Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Martin Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Megan Hume, Charlotte Humphrey, Alasdair Humphries, Amy Humphries, Joanne Humphries, Charlotte Hunt, Fiona Hunt, Jane Hunt, Jonquil Hunt, Kristen Hunt, Luke Hunt, Molly Hunt, Sophie Hunt, Alexandra Hunter, Catherine Hunter, Ewan Hunter, Karl Hunter, Neil Hunter, Ross Hunter, Sophie Hunter, George Huntington, Fuad Huq, Elizabeth Hurditch, Judith Hurdman, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Afreen Hussain, Chreif Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Mohammed Hussain, Muhammad Hussain, Reda Hussain, Rizwana Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Samahir F E M Hussein, Ziad Hussein, Rebecca Hussey, Adiel Haqiq Hussien, Anja Hutchinson, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Nguyen Quang Huy, Thuong Huyen, Tran Bang Huyen, Nguyen Thi Huyen Thuong, Hieu Huynh, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Angeliki Iakovou, Katherine Ibison, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Javed Ibrahim, Mamoun Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Becky Icke, Adetokunbo Idowu Idowu, Muhammad Idrees, Nauman Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Ogechukwu Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, Fatima Mariam Ilyas, La'ali Imam-Gutierrez, Mohamed Iman, Christopher Imray, Haider Imtiaz, Jack Ingham, Jo Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Samantha Inglis-Hawkes, Anne Ingram, Luke Ingram, Tanya Ingram, Nicholas Innes, Peter Inns, Vithusha Inpadhas, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian Petkov Iordanov, Anil Ipe, Javaid Iqbal, Madiha Iqbal, Mishal Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Iziegbe Irabor, Jane Ireland, Jamie Irisari, Robert Irons, Mohannad Irshad, Muhammad S Irshad, 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Julie Jones, Kate E Jones, Kimberly Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nancy Jones, Nicola Jones, Olivia Jones, Paul Jones, Philip H Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Susan Jones, Taya Jones, Thomas Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Michele Jordan, Sarah Jordan, Abi Jose, Litty Jose, Louise Jose, Sanal Jose, Anna Joseph, Gigee Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Tushar Joshi, Benz Josiah, Lijo Joy, Tiffany Joyce, Hong Ju, Adriel Ju Wen Kwek, Andrew Judd, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Nikhil Kadam, Nicole Kader, Ajai Kailey, Matthew Kain, Gail Kakoullis, Azad Kala Bhushan, Richard J K Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Thomas Kalmus Eliasz, Seika Kalsoom, Elisa Kam, 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Diah Sari, Khatija Sarkar, Rahuldeb Sarkar, Sruthi Sarma, Paulo Sarmiento, Zainab Sarwar, Thea Sass, Krishna Satchithananthasivam, Sonia Sathe, Sobitha Sathianandan, Abilash Sathyanarayanan, Lavanya S J P Sathyanarayanan, Thozhukat Sathyapalan, Prakash Satodia, Vera Saulite, Andrew Saunders, Rachel Saunders, Samantha Saunders, Anne Saunderson, Heather Savill, Karishma Savlani, Gauri Saxena, Matthew Saxton, Amrinder Sayan, Ian Sayers, Diane Scaletta, Deborah Scanlon, Jeremy Scanlon, Lyndsay Scarratt, Sean Scattergood, Alvin Schadenberg, Jenna Schafers, Wendy Schneblen, Ella Schofield, Rebecca Schofield, Samuel Schofield, David Scholes, Karen Scholes, Alex Schoolmeesters, Natasha Schumacher, Nicola Schunke, Martin Schuster Bruce, Karin Schwarz, Antonia Scobie, Thomas Scoones, Tim Scorrer, Alex Scott, Alistair Scott, Anne Scott, Catherine Scott, Christine Scott, Emily Scott, Kathyn Scott, Leanne Scott, Martha Scott, Stephen Scott, Timothy Scott, Zoe Scott, Sarah Scourfield, Wendy Scrase, Nicholas A Scriven, Angela Scullion, Therese Scullion, Emily Seager, Cathy Seagrave, Rebecca Seaman, Eleanor Sear, Isabella Seaton, Annette Seatter, Anna Seckington, Joanna Sedano, Gabrielle Seddon, Gemma Sedgwick, Yee Yong See, Muhammad A Seelarbokus, Christopher Sefton, Matias Segovia, Fatima Seidu, Gillian Sekadde, Faye Selby, Georgina Selby, Claire Sellar, Rachael Sellars, Katharine Sellers, Joseph Selley, Victoria Sellick, Gobika Selvadurai, Brintha Selvarajah, Haresh Selvaskandan, Subothini S Selvendran, Jeyakumar Selwyn, Alison Semmens, Gary Semple, Michael Sen, Nandini Sen, Seema Sen, Aditya Sengupta, Niladri Sengupta, Susana Senra, HoJan Senya, Teona Serafimova, Elisa Sernicola, Dheeraj Sethi, Shivam Sethi, Niranjan Setty, Abigail Seward, Teswaree Sewdin, Terri-Ann Sewell, Jack Seymour, Katherine Seymour, Hussam Shabbir, Fiona Shackley, Tariq Shafi, Faiza Shafique, Aashni Shah, Ahmar Shah, Anand Shah, Bhavni Shah, Hussun-Ara Shah, Momin Shah, Neil Shah, Pallav Shah, Priyank Shah, Qasim Shah, Rupal Shah, Sarfaraz H Shah, Snehal Shah, Suraj Shah, Syed Shah, Wajid Shah, Saarma Shahad, Sousan Shahi, Sipan Shahnazari, Najam Shahzad, Muhammad Shahzeb, Aisha Shaibu, Zara Shaida, Amina Y Shaikh, Maliha Shaikh, Rajit Shail, Mariya Shaji, Muhammad Shakeel, Roshni Shakya, Korah Shalan, Nadia Shamim, Ummulbaneen Shamji, Anindya Shams, Kazi Shams, Rasha Shamsah, Thomas Shanahan, Hamed Sharaf, Asir Sharif, Ajay Sharma, Ash Sharma, Bhawna Sharma, Mona Sharma, Ojasvi Sharma, Poonam Sharma, Rajeev Sharma, Sagar Sharma, Sanjeev Sharma, Sarkhara Sharma, Seema D Sharma, Shriv Sharma, Sonal Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Kerry Sharp, Louise M Sharp, Paula Sharratt, Phoebe Sharratt, Katherine Sharrocks, Serene Shashaa, Alexandra Shaw, Christopher Shaw, Daisy Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathon Shaw, Lisa Shaw, Michele Shaw, Tomos G Shaw, Anna Shawcross, James Shawcross, Jill Shawe, Lou Shayler, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, Noorann Sheikh, Benjamin Shelley, Sarah Shelton, Anil Shenoy, Julie Shenton, Sarah Shephardson, Amy Shepherd, Kate Shepherd, Lorna Shepherd, Scott Shepherd, Gareth Sheppard, Rhian Sheppeard, Helen Sheridan, Ray Sheridan, Samuel Sherridan, Leanne Sherris, Susanna Sherwin, Shaad Shibly, Fathimath F Shiham, Cassandra Shilladay, Ben Shillitoe, Delane Shingadia, Chiaki Shioi, Anand Shirgaonkar, Kim Shirley, Helen Shirt, Adebusola Shonubi, Jane Shoote, Ruth Shorrocks, Rob Shortman, Rohan Shotton, Sarah Shotton, Charmaine Shovelton, Ervin Shpuza, Anil Shrestha, Apurba Shrestha, Nora Shrestha, Reema Shrestha, Suchita Shrestha, Karen Shuker, Jonathan Shurlock, Jack Shurmer, Erfanur R Shuvo, Gilbert Siame, Loria Siamia, Moses Siaw-Frimpong, Seshnag Siddavaram, Nasir Siddique, Shahla Siddique, Sohail Siddique, Elaine Siddle, Emma Sidebotham, Jo Sidebottom, Roy Sievers, Katie Siggens, Nyma Sikondari, Ilman Silanas, Sofia V Silva, Claudia Silva Moniz, Malcolm Sim, Theresa Simangan, Vimbai Simbi, Robert Sime, George Simmons, Oliver Simmons, Richard Simms, Laura Simon, Merritt Simon, Natalie Simon, Samantha Simpkins, Angela Simpson, Anna Simpson, Danny Simpson, Georgina Simpson, Joanne Simpson, Kerry Simpson, Maria Simpson, Phillip Simpson, Thomas Simpson, Kathryn Simpson, Simon Sinclair, Cindy Sing, Ankita Singh, Claire Singh, Davinder Singh, Jayaprakash Singh, Jyoti Singh, Lokeshwar Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Saurabh Singh, Shivani Singh, Sumi Singh, Parag Singhal, Bryan Singizi, Vicky Singler, Manas Sinha, Punam Sinha, Sharad Sinha, Utkarsh Sinha, Guy Sisson, Sarah Sithiravel, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darsh Sivakumran, Sivanthi Sivanadarajah, Pasupathy-Rajah Sivasothy, Asok Skaria, Nicole Skehan, Robert Skelly, Orlagh Skelton, Imogen Skene, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Heather Slade, Mark Slade, Lynda Slater, Nicola Slawson, Rachel Slingsby, Andrew Sloan, Brendan Sloan, Derek Sloan, Geraldine Sloane, Malgorzata Slowinska, Benjamin Small, Ellen Small, Samuel Small, Adam Smallridge, Dawn Smalls, Karen Denise Smallshaw, Andy Smallwood, Brittany Smart, Lynne Smart, Justyna Smeaton, Carien Smit, Aileen Smith, Alex Smith, Amanda Smith, Amy Smith, Andrew Smith, Catherine Smith, Chris Smith, Christopher Smith, Coral Smith, Debra Smith, Dominic Smith, Eleanor Smith, Harriet Smith, Hazel Smith, Helen Smith, Jacky Smith, Jessica Smith, Kate Smith, Kerry Smith, Lara Smith, Linda Smith, Lisa Smith, Loren Smith, Maria Smith, Mark Smith, Martha A Smith, Mel Smith, Nicholas Smith, Oliver Smith, Philippa Smith, Rachel Smith, Rebecca Smith, Rheanna Smith, Richard Smith, Sally Smith, Samantha Smith, Stacey Smith, Stephanie Smith, Susan Smith, Tracy Smith, Victoria Smith, Imogen Smith, John Smith, Sue Smolen, Sara Smuts, Naoise Smyth, Annette Snell, David Snell, Luke Snell, Alfred So, Beng So, Michelle Soan, Toluleyi Sobande, Sonia Sobowiec Kouman, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Herminder Sohal, Roy Soiza, Olajumoke Solademi, Babak Soleimani, Amanda Solesbury, Mohamed Soliman, Bernadette Solis, Reanne Solly, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Sven Sommerfield, Govind Soni, Raj Sonia, Temi Sonoiki, Shiu-Ching Soo, Pavandeep Soor, Germander Soothill, Jennifer Soren, Apina Sothinathan, Pragalathan Sothirajah, Jessica Sousa, Najwa Soussi, Donna Southam, David Southern, Iain Southern, Louise Southern, Sara M Southin, Jessica Southwell, Thomas Southworth, Sandra Sowden, Jason Sowter, Claudia Spalding, Enti Spata, Catherine Speare, Katie Spears, Mark Spears, Lynne Speirs, Susan Speirs, Michelle Spence, Niamh Spence, Branwell Spencer, Gisele Spencer, Rebecca Spencer, Sue Spencer, Tom Spencer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Sarah Spray, Janet Spriggs, Oliver Spring, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, Shiva Sreenivasan, K Sri Paranthamen, Rajesh Srikantaiah, Koottalai Srinivasan, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Rhodri Stacey, Sybil Stacpoole, Louise Stadon, William J Stagg, Jocasta Staines, Nikki Staines, Katie Stammers, Roxana Stanciu, Grazyna Stanczuk, Thomas Standley, Brittany Staniforth, Andrew Stanton, Lisa Stanton, Robyn Staples, Simon Stapley, Natalie Staplin, Adam Stark, Elizabeth Starkey, David S Starnes, Michelle Starr, Rachel Stead, Clare Stebbing, Conor Steele, Henry Steer, John Steer, Vergnano Stefania, Paula Stefanowska, Femke Steffensen, Caroline Stemp, Emma Stenson, Alison Stephens, David Stephensen, Elaine Stephenson, Monique Sterrenburg, Jennifer Stevens, Melanie Stevens, Will Stevens, Amy Stevenson, Andrew Stevenson, Lesley Stevenson, Sarah Stevenson, Matthew Steward, Christopher Stewart, Claire Stewart, Colin Stewart, Dobree A Stewart, Katelyn Stewart, Keely Stewart, Kristina Stewart, McKenna Stewart, Melissa Stewart, Rachel Stewart, Richard Stewart, Jo Stickley, Gemma Stiller, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Danielle Stocker, Lynne Stockham, Paul Stockton, Emma Stoddard, Kevin Stoffberg, Chelsea Stokes, Chris Stokes, Ben Stone, Roisin Stone, Sarah Stone, Emma-Jane Stoner, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Catherine Strait, 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, Christian P Subbe, Keerth Subramaniam, Manjula Subramanian, Vaidyanathan Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Peter Sugden, Putri A Suherman, Rudresh Sukla, Anila Sukumaran, Ezoubi Suleiman, Ali Suliman, Fatimah Suliman, Sugrah Sultan, Uun Sumardi, Samyukta Sundar, Radha Sundaram, Reka Sundhar, Edmond Sung, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Nayanika Suresh, Shilpa Suresh, Michael Surtees, C Susan, Danielle Suter, Rohan Suthar, Helen Sutherland, Rachel Sutherland, Rebecca Sutherland, Sara-Beth Sutherland, Dovile Sutinyte, Deborah Sutton, Sam Sutton, Siobhan Sutton, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Rose Swain, Thomas Swaine, Christopher Swales, Carla Swanson-Low, Tirion Swart, Stephen Sweetman, Ealish Swift, Paul Swift, Pauline Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Omair Syed, Catriona Sykes, Daisy Sykes, Eliot Sykes, Luke Sylvester, Declan Symington, Dominic Symon, Andrew Syndercombe, Zoe Syrimi, Jen Syson, Gemma Szabo, Denise Szabó, Tamas Szakmany, Nina Szarazova, Megan Szekely, Adele Szekeres, Matthew Szeto, Kinga Szymiczek, Maria Tadros, Amr Tageldin, Lucy Tague, Hasan Tahir, Muhammad Tahir, Michael Tai, Jennifer Tait, Abigail Takyi, Peter Talbot, Alison Talbot -Smith, James Talbot-Ponsonby, Richard Tallent, Bradley Tallon, Adrian Tan, Bee Theng Tan, Hock Tan, Huey Tan, Jenny Tan, Jun Seng Tan, Keith Tan, WeiTeen Tan, Anand Tana, Alex Tanner, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Anita Tantri, Tm Tanzil-Al-Imran, Hayley Tarft, Priyal Taribagil, Obaid Tarin, Syed Tariq, David Tarpey, Esther Tarr, Lisa Tarrant, Antonia Tasiou, Alex Tate, Margaret L Tate, Matthew Tate, Paul Tate, Kate Tatham, Silvia S Tavares, Vera Tavoukjian, Shao An Isaac Tay, Alexander Taylor, Beverley Taylor, Charlie Taylor, Charlotte A Taylor, David Taylor, Elisabeth Taylor, Holly Taylor, Janet 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, Victoria Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Francesca Teasdale, Jessica Teasdale, Katherine Teasdale, Julie Tebbutt, Caroline Tee, Izla Teeluck, Borja Tejero Moya, Rajni Tejwani, Adam Telfer, Vibha Teli, Jennifer Tempany, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Radoslaw Tereszkowski-Kaminski, Lynne Terrett, Louise Terry, Tesha Islami Monika Tesha, Dariusz Tetla, Shirish Tewari, Daniel Tewkesbury, Joana Texeira, ChiaLing Tey, Miriam Thake, Clare Thakker, Manish Thakker, Jayna Thakrar, Bishal Jung Thakuri, Bhavneet Thamu, Nguyen Thi Thao, Amita Thapa, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Lambrini Theocharidou, Phyu Thet, Kapeendran Thevarajah, Mayooran Thevendra, Nang Thiri Phoo, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Andrew Thomas, Caradog Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Helen Thomas, James Thomas, Jordan L Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Kirsty Thomasson, Rhian Thomas-Turner, Catherine Thompson, Christopher Thompson, Clara Thompson, Emma Thompson, Fiona Thompson, Hilary Thompson, Jessica Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Luke Thompson, Michael Thompson, Orla Thompson, Rebecca Thompson, Roger Thompson, Yolanda Thompson, Nicola Thomson, Patrick Thorburn, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Alice Thornton, Danielle Thornton, Jim Thornton, Richard Thornton, Sara Thornton, Susan Thornton, Thomas Thornton, Tracey Thornton, Christopher Thorpe, Nigel Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Genevieve Thueux, Pinky Thu-Ta, Vicky Thwaiotes, C Louise Thwaites, Guy Thwaites, Simon Tiberi, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Christopher Till, Amanda Tiller, Heather Tiller, John Timerick, Elizabeth Timlick, Alan Timmins, Alison Timmis, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Stephanie Tingley, Nicola Tinker, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Ajay Tirumalai Adisesh, Helen Tivenan, Katarzyna Tluchowska, Helen T-Michael, Anne Todd, Jackie Todd, Shirley Todd, Stacy Todd, Olga Toffoletti, Mohamed Tohfa, Sue Tohill, Melanie Tolson, Ana L Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Jo Tomlinson, Kerry Tomlinson, James Tonkin, Ivan Tonna, Catherine Toohey, Kirsty Topham, Mathew Topping, Audrey Torokwa, Collette Torrance, Omar Touma, Laura Tous Sampol, Ruhaif Tousis, Melissa Tout, Peter Tovey, Gareth Towersey, Jill Townley, Richard Tozer, Dang Khoa Tran, Hien Tran, Huyen Bang Tran, Michelle Tran, Nguyen Bao Tran, Van Giang Tran, Van Kien Tran, Helen Tranter, Jenny Travers, Christopher Travill, Sarah Traynor, Leanne Trethowan, Estefania Treus Gude, Mary Trevelyan, Nicola A Trewick, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Alex Trimmings, Tom Trinick, Kate Trivedi, Sven Troedson, Emily Tropman, Amy Trotter, Spyridon Trous, Helen Trower, Madeleine Trowsdale Stannard, Nigel Trudgill, Robert Truell, Nick Truman, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Tan Tsawayo, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Merika Tsitsi, Simon Tso, Natasha Tucker, Sally Tucker, Stephanie Tucker, Daisy E Tudor, Aisha Tufail, Jess Tuff, Jemma Tuffney, Redmond Tully, Tulus Tulus Satriasih, Grace Tunesi, Killiam Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Georgina Turner, Kate Turner, Kelly Turner, Kim Turner, Lucy Turner, Lynne C Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Sarah Turner, Victoria Turner, Ian Turner-bone, Sharon Turney, Jon Turvey, Conor Tweed, David Tweed, Rebecca Twemlow, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Amanda Tyler, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Ioannis Tzinieris, A Wahid Uddin, Mohammad S Uddin, Ruhama Uddin, Ruzena Uddin, Jacinta Ugoji, Edith N Ukaegbu, Mazhar Ul Haq, Waqar Ul Hassan, Zia Ul-Haq, Salamat Ullah, Sana Ullah, Sanda Ullah, Ju Um, Athavan Umaipalan, Anil Umate, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Ben Ummat, Emma Underhill, Charlotte Underwood, Jonathan Underwood, Adam Unsworth, Veerpal Uppal, Veerpal S Uppal, Gerry Upson, Masood Ur Rasool, Alison Uriel, Sebastian Urruela, Hiromi Uru, Jess Usher, Miranda Usher, Rebecca Usher, Alexandra Usher-Rea, Andrew Ustianowski, Effua Usuf, Febriansyah Nur Utomo, Hiromi Uzu, Linda C Vaccari, Uddhav Vaghela, Abhay Vaidya, Denny Vail, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Pramodh Vallabhaneni, Nick Vallotton, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Sarah Van Blydenstein, Lucia van Bruggen, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne van Koutrik, Alexander Van Loggerenberg, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Piyush Vanmali, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Anna-Nektaria Varouxaki, Resti Varquez, Valeria Vasadi, Olivia Vass, Katherine Vassell, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Sue Vaughan, Heloyes Vayalaman, Darini Vayapooree, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Aravind Velugupati, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Michelle Venter, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Liberty Verueco, Jerik Verula, Anna Veterini, Natalie Vethanayagam, Shambavi Vettikumaran, Lucy Veys, Carinna Vickers, Saji Victor, SImpson Victoria, Celine P Vidaillac, Jennifer Vidler, Bavithra Vijayakumar, Vinod W Vijayaraghavan Nalini, Brigita Vilcinskaite, Alicija Vileito, Neringa Vilimiene, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Olivia Vincent, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Martina Vitaglione, Karunakaran Vithian, Sorice Vittoria, Sankkita Vivekananthan, Elena Vlad, Ben Vlies, Linda von Oven, Claire Vooght, Kim Thi Vu Thai, Kritchai Vutipongsatorn, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Phillip Wade, Jonathan Wadsley, Kirsten Wadsworth, Syed E I Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Alicia Waite, Rachel Wake, Alice Wakefield, William Wakeford, Fiona Wakinshaw, Emma Waldeck, Andrew Walden, Lorna Walding, Alexandria Waldron, Joanne Waldron, Emma Wales, Batool Wali, Danielle Walker, Gemma Walker, Harriet Walker, Ian Walker, Kevin Walker, Kim Walker, Lauren Walker, Linda Walker, Lynne Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Sara Walker, Susan Walker, Gillian Wallace, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Matthew Wallis, Emma Walmsley, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Maisie Walton, Michael Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Junita Wanda, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Shentong Wang, Deborah Warbrick, Samantha Warburton, Christopher Ward, Deborah Ward, Emma Ward, Hannah Ward, Janice Ward, Joanna Ward, Luke Ward, Nicola Ward, Rachael Ward, Thomas Ward, Tom Ward, Scott A Warden, Gibril Wardere, Steve Wardle, Hassan Wardy, Gareth Waring, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Rebecca Warren, Yolanda Warren, Davina Warrender, Hannah Warren-Miell, Adilia Warris, Gill Warwick, Helen Wassall, Sean Wasserman, Elizabeth Wasson, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Abigail Watkin, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Abigail Watson, Adam J R Watson, Ekaterina Watson, Eleanor Watson, Felicity Watson, J G R Watson, Louisa Watson, Paul Watson, Rebecca Watson, Robert Watson, Kathleen Watson, Malcolm Watters, Donna Watterson, Khairiah Wattimena, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Matthew Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Chloe Webb, Claire Webb, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Jemma Webster, Tim Webster, Jordan Wedlin, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Emma Welch, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Benjamin Welham, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Victoria Wenn, Lauren Wentworth, Joan Wesonga, Kate Wesseldine, Joe West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Kelly Westwood, Sharon Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Andrew White, Ayesha White, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Nikki White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Kelly Whitehorn, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Louiza Whiteley, Sophie Whiteley, Rachael Whitham, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Ashleigh Wignall, Christopher Wignall, Annamaria Wilce, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Ben Wild, Laura Wild, Stephen Wild, Michael Wilde, Laura Wilding, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Anna Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Eleri Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, Heledd Williams, James Williams, Jennie Williams, Jill Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Mandy Williams, Marie Williams, Mark Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachel Williams, Robin Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Steffan Williams, Tamanna Williams, Tania Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Jodie Williamson, Rachel Williamson, Helen Williamson, Elaine Willis, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Jayne Willson, Alison Wilson, Andrea Wilson, Anna Wilson, Antoinette Wilson, Billy Wilson, David Wilson, Imogen Wilson, James Wilson, Karen Wilson, Kate Wilson, Kristy-Ann Wilson, Lucinda Wilson, Mark Wilson, Stephen Wilson, Toni Wilson, John Wilson, Khin Lei Yee Win, Marlar Win, Than Win, Tin Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Stuart Winearl, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Joseph Winterton, Hannah Winwood, Jack Wischhusen, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Tabitha WIshlade, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Chi-Man Wong, Edwin Wong, Jessica S Y Wong, Kit Y Wong, Mei Yin Wong, Nick Wong, Sam Wong, Ting Wong, Aaron B Wongkyezeng, Amanda Wood, Caroline Wood, Dianne Wood, Fiona Wood, Gordon Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Madeleine Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Myles Woodman, Stephen Woodmansey, Charlotte Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Holly Wright, Imogen Wright, Lianne Wright, Rachel Wright, Sarah Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Subie Wurie, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Bingru E Xia, Zhongyang Xia, Effua Yacoba, Santosh Yadav, Masseh Yakubi, May Yan, Yuuki Yanagisawa, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Jessica Ye, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Lam Minh Yen, Alastair Yeoh, Chun Yu Yeung, Peter Yew, Durgesh Yewatkar, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Hartantri Yovita, Chrissie Yu, Jack S J Yuan, Nindya Yufaniaputri, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Mahrukh Zainab, Thornton Zak, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Marcelina Zawadzka, Mohammed Zayed, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Darius Zeinali, Jing Zhang, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eva Zincone, Garikai Zindoga, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Letizia Zitter, Arkadiusz Zmierczak, Garazi Zubikarai, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, and Group, RECOVERY Collaborative

Subjects
Adult, Male, Hypoxia/etiology, SARS-CoV-2, COVID-19, 3rd-DAS, General Medicine, Adrenal Cortex Hormones/therapeutic use, AC, Dexamethasone/therapeutic use, Hospitals, Oxygen, Treatment Outcome, SDG 3 - Good Health and Well-being, MCP, Humans, Female
Abstract

Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation Findings Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). Interpretation In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Funding UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

Published
2023
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43. Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE

Author

Maria Otth, Eva Brack, Pamela R Kearns, Olga Kozhaeva, Marko Ocokoljic, Reineke A Schoot, Gilles Vassal, Federica Achini, Adriana Balduzzi, Maja Beck Popovic, Auke Beishuizen, Luca Bergamaschi, Andrea Biondi, Franck Bourdeaut, Elena Braicu, Jesper Brok, Laurence Brugières, Amos Burke, Gabriele Calaminus, Michela Casanova, Marie-Louise Choucair, Morgane Cleirec, Selim Corbaciouglu, Maria Genoveva Correa Llano, Teresa De Rojas, Nerea Domínguez Pinilla, Caroline Elmaraghi, Andrea Ferrari, Alexander Fossa, Nathalie Gaspar, Nikolas Herold, Kyriaki Karapiperi, Maarja Karu, Mimi Kjærsgaar, Fabian Knörr, Christa Koenig, Izabela Kranjcec, Malgorzata Krawczyk, Kai Lehmberg, Thomas Lehrnbecher, Maaike Lunesink, Davide Massano, Nuša Matijasic, Hans Merks, Markus Metzler, Anthony Michalski, Milen Minkov, Bruce Morland, Naghmeh Niktoreh, Elena Oltenau, Daniel Orbach, Cormac Owens, Smaragda Papachristidou, Claudia Pasqualini, Maja Pavlovic, Paula Perez Albert, Fiona Poyer, Ivana Radulovic, Dirk Reinhardt, Joana Rebelo, Eva Roser, Ida Russo, Katrin Scheinemann, Christina Schindera, Martin Schrappe, Astrid Sehested, Jalid Sehouli, Filippo Spreafico, Sandra J Strauss, Janine Stutterheim, Karel Svojgr, Vasiliki Tzotzola, Roelof Van Ewijk, Arnauld Verschuur, Ajay Vora, Willi Woessmann, Olga Zajac-Spychala, Michel Zwaan, Maria, O, Eva, B, Pamela R, K, Olga, K, Marko, O, Reineke A, S, Gilles, V, Achini, F, Balduzzi, A, Beck Popovic, M, Beishuizen, A, Bergamaschi, L, Biondi, A, Bourdeaut, F, Braicu, E, Brok, J, Brugières, L, Burke, A, Calaminus, G, Casanova, M, Choucair, M, Cleirec, M, Corbaciouglu, S, Genoveva Correa Llano, M, De Rojas, T, Domínguez Pinilla, N, Elmaraghi, C, Ferrari, A, Fossa, A, Gaspar, N, Herold, N, Karapiperi, K, Karu, M, Kjærsgaar, M, Knörr, F, Koenig, C, Kranjcec, I, Krawczyk, M, Lehmberg, K, Lehrnbecher, T, Lunesink, M, Massano, D, Matijasic, N, Merks, H, Metzler, M, Michalski, A, Minkov, M, Morland, B, Niktoreh, N, Oltenau, E, Orbach, D, Owens, C, Papachristidou, S, Pasqualini, C, Pavlovic, M, Perez Albert, P, Poyer, F, Radulovic, I, Reinhardt, D, Rebelo, J, Roser, E, Russo, I, Scheinemann, K, Schindera, C, Schrappe, M, Sehested, A, Sehouli, J, Spreafico, F, J Strauss, S, Stutterheim, J, Svojgr, K, Tzotzola, V, Van Ewijk, R, Verschuur, A, Vora, A, Woessmann, W, Zajac-Spychala, O, and Zwaan, M

Subjects
Europe, Adolescent, Oncology, Neoplasms, Childhood cancer, essential medicines, SIOPe, Humans, Antineoplastic Agents, Child, Medical Oncology, Drugs, Essential
Abstract

Background: Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology (SIOPE) Essential Anticancer Medicines Project was to provide a list of anticancer medicines that are considered essential in the treatment of paediatric cancers to help ensure their continuous access to all children and adolescents with cancer across Europe. Methods: This pan-European project, done between Jan 20, 2020, and Feb 18, 2022, was designed to be a systematic collection and review of treatment protocols and strategies that are used to treat childhood cancer in Europe. We formed 16 working groups on the basis of paediatric cancer types, and which were based on the existing SIOPE Clinical Trial Groups. Workings groups consisted of representatives from the SIOPE Clinical Trial Groups, Young SIOPE members, and senior paediatric oncology experts. Each group collected existing treatment protocols that are used to treat the respective cancer types in Europe. Medicines from the standard group of each protocol were extracted. For medicines not on the WHO Essential Medicines List for children (EMLc) 2017, working groups did a literature search to determine whether the medicines should be defined as essential, promising, or neither essential nor promising. Each group provided an individual summary, and all medicines that were considered essential by at least one group were combined in a joint list. Findings: The working groups identified 73 treatment protocols used in Europe and defined 66 medicines as essential. For several newer medicines, such as kinase inhibitors or tisagenlecleucel, the supporting evidence was insufficient to consider them essential, so these medicines were defined as promising. 25 medicines were considered promising by at least one working group. 22 (33%) of the 66 essential and none of the promising medicines were included in the WHO EMLc 2017. The WHO EMLc 2021 included two new medicines (everolimus and vinorelbine) following applications we made as a result of this project. Interpretation: Medicines that were defined as essential within this project should be available for the treatment of childhood and adolescent cancer continuously and across Europe. This list can be used to support and guide stakeholders and policy makers in negotiations on a national and European level regarding shortages, accessibility, and affordability of these medicines. Funding: None.

Published
2022
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44. Longitudinal associations between impulsivity and alcohol and cannabis use frequency, quantity, and problems among military veterans

Author

Nathan T. Kearns, Rachel L. Gunn, Angela K. Stevens, Benjamin L. Berey, and Jane Metrik

Subjects
Psychiatry and Mental health, Clinical Psychology, Adolescent, Alcohol Drinking, Substance-Related Disorders, Impulsive Behavior, Humans, Medicine (miscellaneous), Alcohol-Related Disorders, Veterans, Cannabis
Abstract

Impulsivity is an established etiological risk factor for alcohol- and cannabis-related outcomes. However, limited work has focused on longitudinal associations between multiple trait impulsivity facets and indices of alcohol and cannabis use among military veterans-a contextually distinct population that evidence unique impulsive personality traits and substance use patterns.A structural equation model (SEM) examined longitudinal associations between five UPPS-P impulsivity facets measured at baseline and six indices of alcohol and cannabis use (i.e., frequency, quantity, and problems) measured at 1-year follow-up among 361 returning Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) veterans.Findings indicated baseline sensation seeking was significantly positively associated with 1-year alcohol use frequency (β = .18); baseline negative urgency was positively associated with alcohol use problems (β = .31); and baseline lack of perseverance (β = .25) and sensation seeking (β = .21) were positively associated with 1-year cannabis use problems. None of the baseline impulsivity facets were associated with 1-year alcohol use quantity, cannabis use frequency, or cannabis use quantity.Results provide preliminary support that impulsivity may play a unique role in understanding alcohol- and cannabis-related problems over time among veterans. Further, results suggest that specific impulsivity facets are prospectively associated with cannabis problems (i.e., lack of perseverance and sensation seeking) and alcohol problems (i.e., negative urgency). Findings reinforce the importance of differentially evaluating impulsivity-substance use associations within contextually distinct populations (e.g., adolescent, veteran), and highlight potentially meaningful intervention targets among veterans. However, replication is needed with stronger temporal controls and more diverse veteran subsamples. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Published
2022
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45. Qualitative analysis of hospital patient narratives of warning signs on the day of their suicide attempt

Author

Kenneth R, Conner, Jaclyn C, Kearns, and Lauren M, Denneson

Subjects
Adult, Male, Psychiatry and Mental health, Alcohol Drinking, Risk Factors, Humans, Female, Suicide, Attempted, Hospitals, Suicidal Ideation
Abstract

Research on warning signs, defined as acute risk factors for suicide or suicide attempt, has been slow due to the difficulty of examining the hours and minutes preceding suicidal behavior. This study sought to identify new warning signs and to re-examine warning signs that have been proposed.Narrative stories of adult patients with substance use problems hospitalized following a suicide attempt were transcribed. The narrative segments describing the 24-h period prior to suicide attempt were examined with directed qualitative content analysis using codes based on prior literature and new codes developed inductively.The sample (N = 35) was mean age = 40, 51% female, and 49% White non-Hispanic. Analysis of the transcripts of the 24-h periods (M word count = 637) yielded a broad range of cognitive (e.g., cognitive disturbance such as rumination), behavioral (e.g., alcohol use), emotional (e.g., dramatic mood changes), and social (e.g., social withdrawal) warning signs, along with a small number of cognitions and behaviors that appeared to mark a dangerous shift to acute preparation and intent for attempt, for example 'self-persuasion to attempt suicide.'We posit that a broad range of cognitive, behavioral, emotional, and social warning signs increase acute risk for suicidal behavior by creating the conditions for a shift to acute preparation and intent, a highly potent category of warning signs.

Published
2022
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46. Recommendations for anatomical structures to identify on ultrasound for the performance of intermediate and advanced blocks in ultrasound-guided regional anesthesia

Author

Toby Ashken, James Bowness, Alan James Robert Macfarlane, Lloyd Turbitt, Boyne Bellew, Nigel Bedforth, David Burckett-St Laurent, Alain Delbos, Kariem El-Boghdadly, Nabil M Elkassabany, Jenny Ferry, Ben Fox, James L H French, Calum Grant, Ashwani Gupta, Rajnish K Gupta, Yavuz Gürkan, Nat Haslam, Helen Higham, Rosemary M G Hogg, David F Johnston, Rachel Joyce Kearns, Clara Lobo, Sonya McKinlay, Edward R Mariano, Stavros Memtsoudis, Peter Merjavy, Madan Narayanan, J Alison Noble, David Phillips, Meg Rosenblatt, Amy Sadler, Maria Paz Sebastian, Eric S Schwenk, Alasdair Taylor, Athmaja Thottungal, Luis Fernando Valdés-Vilches, Thomas Volk, Simeon West, Morné Wolmarans, Jonathan Womack, and Amit Pawa

Subjects
Anesthesiology and Pain Medicine, pain management, lower extremity (regional anesthesia), Anesthesia, Conduction, Humans, ultrasonography, Peripheral Nerves, General Medicine, regional anesthesia, upper extremity (regional anesthesia), Ultrasonography, Interventional, Ultrasonography
Abstract

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for “orientation scanning” (the dynamic process of acquiring the final view) and for “block view” (which visualizes the block site and is maintained for needle insertion/injection). A “strong recommendation” was made if ≥75% of participants rated any structure as “definitely include” in any round. A “weak recommendation” was made if >50% of participants rated it as “definitely include” or “probably include” for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a “strong recommendation” was made for 60 structures on orientation scanning and 44 on the block view. A “weak recommendation” was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Published
2022
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47. Caring for adults with hip pain

Author

Larry, Munger, Amy Karen, Moore, Gary A, Kearns, and Shelly, Seth

Subjects
Adult, Advanced and Specialized Nursing, Humans, Pain, Assessment and Diagnosis, Emergency Nursing, LPN and LVN, Critical Care Nursing, Arthralgia, Pain Measurement
Abstract

This article discusses the pathophysiology, assessment techniques, and management of hip pain in adults and the role of nurses in caring for patients with hip pain.

Published
2022
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48. Tourniquet Use During Open Reduction and Internal Fixation of Ankle Fractures – A Systematic Review and Meta-Analysis

Author

Martin S. Davey, Matthew G. Davey, Eoghan T. Hurley, and Stephen R. Kearns

Subjects
Adult, Male, Fracture Fixation, Internal, Open Fracture Reduction, Treatment Outcome, Humans, Pain, Female, Orthopedics and Sports Medicine, Surgery, Middle Aged, Tourniquets, Ankle Fractures
Abstract

The intra-operative use of tourniquet in open reduction and internal fixation (ORIF) of ankle fractures remains a topic of debate. The purpose of this study was to perform a systematic review and meta-analysis of randomized control trials (RCTs) comparing clinical outcomes of patients undergoing ankle ORIF with tourniquet use versus a control group where no tourniquet was used. A systematic review was performed with reference to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines of the Pubmed, Scopus, Embase, and Cochrane Library databases. Studies were included if they were an RCT comparing tourniquet and no-tourniquet in ankle ORIF. Meta-analysis was performed using RevMan, and p-value.05 was considered to be statistically significant. On completion of the literature search, a total of 4 RCTs including 350 ankles (52.6% males), with a mean age of 47.1 ± 5.7 years were included. There were 173 patients in the tourniquet group (T), versus 177 patients in the no tourniquet control group (NT), with nonsignificant differences between the groups for age, gender and body mass index demographics (all p.05). There were significantly shorter duration of surgery, with significantly higher patient-reported rates of pain levels at day 2 postoperatively (both p.001) in the T group. Additionally, there were significantly greater ranges of ankle motion at 6 weeks postoperatively (p = .03), with nonsignificant differences reported incidence of wound infections and deep vein thrombosis (p = .056 and p = .130 respectively) between the groups. In conclusion, current evidence suggests that although intraoperative tourniquet usage in cases of ankle ORIF results in significant reductions in duration of surgery, this may be at the expense of higher patient-reported pain scores and reduced range of motion postoperatively.

Published
2022
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49. The cost-effectiveness of brigatinib in adult patients with ALK inhibitor–naive ALK-positive non–small cell lung cancer from a US perspective

Author

Holly, Cranmer, Isabella, Kearns, Melanie, Young, Michael J, Humphries, and David, Trueman

Subjects
Adult, Lung Neoplasms, Cost-Benefit Analysis, Health Policy, Pharmaceutical Science, Pharmacy, Organophosphorus Compounds, Pyrimidines, Crizotinib, Pharmaceutical Preparations, Carcinoma, Non-Small-Cell Lung, Humans, Anaplastic Lymphoma Kinase, Protein Kinase Inhibitors
Published
2022
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50. Comparing 1-year and 10-year whole blood metal ion results following Birmingham hip resurfacing for osteoarthritis

Author

Scott J, Watt Kearns, Jonathan, Bourget-Murray, Kelly, Johnston, and Jason, Werle

Subjects
Chromium, Male, Arthroplasty, Replacement, Hip, Cobalt, Prosthesis Design, Osteoarthritis, Hip, Prosthesis Failure, Metals, Osteoarthritis, Metal-on-Metal Joint Prostheses, Humans, Female, Surgery, Hip Prosthesis, Retrospective Studies
Abstract

Patients with metal-on-metal hip arthroplasty may develop adverse reactions to metal debris that can lead to clinically concerning symptoms, often needing revision surgery. As such, many regulatory authorities advocate for routine blood metal ion measurement. This study compares whole blood metal ion levels obtained 1 year following Birmingham Hip Resurfacing (BHR) to levels obtained at a minimum 10-year follow-up.A retrospective chart review was conducted to identify all patients who underwent a BHR for osteoarthritis with a minimum 10-year follow-up. Whole blood metal ion levels were obtained at final follow-up in June 2019. These results were compared with patients' metal ion levels at 1 year.Of the 211 patients who received a BHR, 71 patients (54 males and 17 females) had long-term metal ion levels assessed (mean follow-up 12.7 ± 1.4 yr). The mean cobalt and chromium levels for patients with unilateral BHRs (43 males and 13 females) were 3.12 ± 6.31 μg/L and 2.62 ± 2.69 μg/L, respectively; for patients with bilateral BHRs (11 males and 4 females) cobalt and chromium levels were 2.78 ± 1.02 μg/L and 1.83 ± 0.65 μg/L, respectively. Thirty-five patients (27 male and 8 female) had metal ion levels tested at 1 year postoperatively. The mean changes in cobalt and chromium levels were 2.29 μg/L (Our results suggest that regular metal ion testing as per current regulatory agency guidelines may be impractical for asymptomatic patients. Metal ion levels may in fact have little utility in determining the risk of failure and should be paired with radiographic and clinical findings to determine the need for revision.

Published
2022
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