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1,153 results on '"S. McKay"'

101. The interaction of APOE genotype and amyloid‐β PET predicts PET but not CSF measures of tauopathy in regions of high APOE mRNA expression

Author

Aylin Dincer, Charles D. Chen, Nicole S. McKay, Austin A. McCullough, Shaney E. Flores, Sarah J. Keefe, Stephanie A. Schultz, Rebecca L. Feldman, Russ C. Hornbeck, Carlos Cruchaga, David M. Holtzman, John C. Morris, Tammie L.S. Benzinger, and Brian A. Gordon

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

102. Preclinical Alzheimer disease pathology partially mediates the relationship between cortical thickness and cognitive control

Author

Nicole S. McKay, Aylin Dincer, Vidushri Mehrotra, Andrew J. Aschenbrenner, David A. Balota, Russ C. Hornbeck, John C. Morris, Tammie L.S. Benzinger, and Brian A. Gordon

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

103. White matter neuroinflammation correlates cognition in preclinical Alzheimer disease

Author

Qing Wang, Suzanne E. Schindler, Gengsheng Chen, Nicole S. McKay, Jingxia Liu, Shaney E. Flores, Sicheng Wang, Jason Hassenstab, John C. Morris, Yong Wang, and Tammie L.S. Benzinger

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

104. HIV-infection and cocaine use regulate semen extracellular vesicles proteome and miRNAome in a manner that mediates strategic monocyte haptotaxis governed by miR-128 network

Author

Heather S. McKay, Steven Kopcho, Hussein Kaddour, Marta Epeldegui, Eun Young Kim, Chioma M. Okeoma, Nadia Shouman, Victor Paromov, Jack T. Stapleton, Yuan Lyu, Joseph B. Margolick, Siddharth Pratap, Chandravanu Dash, and Jeremy J. Martinson

Subjects
Proteomics, History, Polymers and Plastics, Proteome, Physiology, Cell, HIV Infections, Comorbidity, Pharmacology, Industrial and Manufacturing Engineering, Monocytes, Extracellular matrix, miR-128-3p, Substance Misuse, Cocaine, 80 and over, 2.1 Biological and endogenous factors, Gene Regulatory Networks, Aetiology, Aged, 80 and over, Chemotaxis, virus diseases, Middle Aged, medicine.anatomical_structure, Infectious Diseases, Molecular Medicine, HIV/AIDS, Infection, Systems biology, Biotechnology, Adult, Biochemistry & Molecular Biology, Adolescent, Clinical Sciences, Biology, Article, Haptotaxis, Cellular and Molecular Neuroscience, Young Adult, Extracellular Vesicles, Small RNA-Seq, Semen, Extracellular, medicine, Humans, Business and International Management, Molecular Biology, Aged, Base Sequence, Monocyte, Prevention, Neurosciences, Cell Biology, In vitro, MicroRNAs, HIV-1, Biochemistry and Cell Biology, Drug Abuse (NIDA only)
Abstract

Background: Extracellular vesicles (EVs) are mediators of horizontal transfer of bioactive molecules between cells and regulators of cell-cell interaction. EV-mediated cell-cell interactions play roles in physiological and pathophysiological conditions. However, the effect of pathogens and cocaine use on EV composition and function are not fully understood. Methods: We obtained 64 seminal plasma specimens from HIV-1-uninfected (HIV—and HIV-1-infected (HIV+) participants who used cocaine (COC—) or did not use cocaine (COC+). The participants were divided into 4 clinical groups (16 per group) denoted as HIV–COC–, HIV–COC+, HIV+COC–, and HIV+COC+ were used. The seminal plasma was used to isolate EVs (SEVs) by differential centrifugation and PPLC-based size exclusion chromatography (SEC) as previously described. We used the SEV to study how HIV infection and cocaine regulate the repertoire and functions of EV-associated proteins, miRNA, and their interactome. After paired proteomics and small RNA-Sequencing (sRNA-Seq) analyses, we employed an in vitro two-dimensional-substrate single cell haptotaxis assay for quantitative assessment of the effect of different SEV on monocyte haptotaxis. Finally, we functionalized SEV with exogenous miR-128 to directly address the role of SEV-associated miR-128 on monocyte haptotaxis. Findings: Systems biology and multi-omics analysis showed that HIV infection (HIV+) and cocaine (COC) use (COC+) promote the release of SEV with dysregulated extracellular proteome (exProtein), miRNAome (exmiR), and exmiR networks. Integrating SEV proteome and miRNAome revealed a significant decrease in the enrichment of disease-associated, brain-enriched, and HIV-associated miR-128-3p (miR-128) in HIV+COC+ SEV along with a concomitant increase in miR-128 targets—PEAK1 and RND3/RhoE. Two-dimensional-substrate single cell haptotaxis showed that in the presence of HIV+COC+ SEVs, contact guidance provided by the extracellular matrix (ECM, collagen type 1) network facilitated far-ranging haptotactic cues that guided monocytes over longer distances. Functionalizing SEVs with miR-128 mimic revealed that the strategic changes in monocyte haptotaxis are in large part the result of SEV-associated miR-128. Interpretation: Compositionally and functionally distinct HIV+COC+ and HIV–COC– SEVs and their exmiR networks may provide cells relevant but divergent haptotactic guidance in the absence of chemotactic cues, under both physiological and pathophysiological conditions. Funding Statement: This work was supported by grants from the National Institute on Drug Abuse (NIDA), grants DA042348, DA050169 and DA053643 to C.M.O. Declaration of Interests: None to declare. Ethics Approval Statement: This study was conducted according to University regulations approved by Stony Brook University Institutional Review Boards (IRB # 201608703) using de-identified human specimens obtained through the Multicenter AIDS Cohort Study (MACS).

Published
2021

108. Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure

Author

Anna S. Cosgrave, Jennifer S. McKay, Vivien Bubb, Richard Morris, John P. Quinn, and Thimmasettappa Thippeswamy

Subjects
Epilepsy, Kainic acid, Neuroprotection, ADNP, Nitric oxide synthase blockers, cGMP, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Activity-dependent neuroprotective protein (ADNP) is widely distributed in the cytoplasm of neurons and astrocytes of the hippocampus. Kainic acid (KA)-induced seizures increases neuronal nitric oxide synthase (nNOS) in neurons and inducible NOS (iNOS) in glia cells which coincides with a reduction in ADNP in the hippocampus. Inhibitors of NOS or soluble guanylyl cyclase (sGC) activity reduce ADNP under basal conditions in the absence of seizures. Treating animals with these inhibitors prior to KA-induced seizure, in particular, L-NAME (NG-nitro-l-arginine methyl ester), advances the onset of the first seizure but reverses the loss of ADNP by 3 days after the first seizure. This suggests that the NO-cGMP pathway has a role in regulating ADNP under both basal physiological conditions and in the pathophysiological changes produced during epileptogenesis.

Published
2008
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109. Do blood-borne calcifying nanoparticles self-propagate?

Author

Grace Mathew, David S McKay, and Neva Çiftçioglu

Subjects
Medicine (General), R5-920
Abstract

Grace Mathew1, David S McKay2, Neva Çiftçioglu21Nanobac Pharmaceuticals Inc, Johnson Space Center, Houston, TX, USA; 2NASA Johnson Space Center, Houston, TX, USAAbstract: The nanotechnology industry is currently in the process of producing new nanoparticles. The biological activity of nanoparticles including adverse as well as beneficial effects tends to increase as their size decreases. The smaller the particles are, the greater their bioactivity and toxicity. Thus, one can easily conjecture the impact of a nanoparticle if it could also self-replicate. This in vitro study reveals the self-propagating ability of unique calcifying nanoparticles (CNP) that can be as small as 50 nm in size and found in blood, blood products, and calcified soft tissues. Although specific detection techniques, morphological characteristics and biomineralizing properties of CNP are well established, their genomic information and self-propagating capability have always been challenged. The objective of this study is to document the propagation of CNP under physiological conditions, using inverted light microscopy (LM) and the Biostation IM time-lapse imaging system. Their detailed morphological structure was examined using scanning (SEM) and transmission (TEM) electron microscopy. This present study, in conjunction with previous findings of metabolic activity, antibiotic sensitivity, antibody specificity, morphological aspects and infectivity, validates CNP as self-replicators. Therefore these sterile-filterable, blood-borne nanoparticles should be of concern to the nanomedicine industry.Keywords: calcifying nanoparticles, time-lapse photography, self-replication, apatite

Published
2008

110. Geospatial Suitability Indices Toolbox (GSI Toolbox)

Author

S. McKay, Christina L. Saltus, and Todd M. Swannack

Subjects
Geospatial analysis, Database, Computer science, computer.software_genre, computer, Toolbox
Abstract

Habitat suitability models are widely adopted in ecosystem management and restoration, where these index models are used to assess environmental impacts and benefits based on the quantity and quality of a given habitat. Many spatially distributed ecological processes require application of suitability models within a geographic information system (GIS). Here, we present a geospatial toolbox for assessing habitat suitability. The Geospatial Suitability Indices (GSI) toolbox was developed in ArcGIS Pro 2.7 using the Python® 3.7 programming language and is available for use on the local desktop in the Windows 10 environment. Two main tools comprise the GSI toolbox. First, the Suitability Index Calculator tool uses thematic or continuous geospatial raster layers to calculate parameter suitability indices based on user-specified habitat relationships. Second, the Overall Suitability Index Calculator combines multiple parameter suitability indices into one overarching index using one or more options, including: arithmetic mean, weighted arithmetic mean, geometric mean, and minimum limiting factor. The resultant output is a raster layer representing habitat suitability values from 0.0 to 1.0, where zero is unsuitable habitat and one is ideal suitability. This report documents the model purpose and development as well as provides a user’s guide for the GSI toolbox.

Published
2021

111. Pericytes are progenitors for coronary artery smooth muscle

Author

Katharina S Volz, Andrew H Jacobs, Heidi I Chen, Aruna Poduri, Andrew S McKay, Daniel P Riordan, Natalie Kofler, Jan Kitajewski, Irving Weissman, and Kristy Red-Horse

Subjects
cardiovascular development, vascular smooth muscle, Notch signaling, Medicine, Science, Biology (General), QH301-705.5
Abstract

Epicardial cells on the heart’s surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data are the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveals a new potential cell type for targeting during cardiovascular disease.

Published
2015
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112. The brain-derived neurotrophic factor (BDNF) val66met polymorphism differentially affects performance on subscales of the Wechsler memory scale – third edition (WMS-III)

Author

Yvette Nicole Lamb, Christopher S. Thompson, Nicole S. McKay, Karen E. Waldie, and Ian J. Kirk

Subjects
Memory, Recognition (Psychology), Neurogenetics, Recall, BDNF Val66Met, Psychology, BF1-990
Abstract

Single nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the catechol-O-methyltransferase (COMT) gene influence brain structure and function, as well as cognitive abilities. They are most influential in the hippocampus and prefrontal cortex (PFC), respectively. Recall and recognition are forms of memory proposed to have different neural substrates, with recall having a greater dependence on the PFC and hippocampus. This study aimed to determine whether the BDNF val66met or COMT val158met polymorphisms differentially affect recall and recognition, and whether these polymorphisms interact. A sample of 100 healthy adults was assessed on recall and familiarity-based recognition using the Faces and Family Pictures subscales of the Wechsler Memory Scale – Third Edition (WMS-III). COMT genotype did not affect performance on either task. The BDNF polymorphism (i.e. met carriers relative to val homozygotes) was associated with poorer recall ability, while not influencing recognition. Combining subscale scores in memory tests such as the WMS might obscure gene effects. Our results demonstrate the importance of distinguishing between recall and familiarity-based recognition in neurogenetics research.

Published
2015
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113. Adolescent Male Athletes: Body Image, Diet, and Exercise.

Author

Parks, Pamela S. McKay and Read, Marsha H.

Abstract

Investigates and compares football players' (n=44) and cross-country runners' (n=30) body image concerns, attitudes toward eating, and reasons for exercising. Results revealed significant differences. Football players reported a more positive body image, whereas runners indicated a greater concern for weight control and more disordered eating patterns. (RJM)

Published
1997

114. Baseline Microglial Activation Correlates With Brain Amyloidosis and Longitudinal Cognitive Decline in Alzheimer Disease

Author

Qing Wang, Gengsheng Chen, Suzanne E. Schindler, Jon Christensen, Nicole S. McKay, Jingxia Liu, Sicheng Wang, Zhexian Sun, Jason Hassenstab, Yi Su, Shaney Flores, Russ Hornbeck, Lisa Cash, Carlos Cruchaga, Anne M. Fagan, Zhude Tu, John C. Morris, Mark A. Mintun, Yong Wang, and Tammie L.S. Benzinger

Subjects
Neurology, Receptors, GABA, Alzheimer Disease, Brain, Humans, Cognitive Dysfunction, Neurology (clinical), Amyloidosis, Microglia
Abstract

Background and ObjectivesThis study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.MethodsTwenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of Aβ42, Aβ42/Aβ40 ratio, tau phosphorylated at position 181 (p-tau181), and total tau (t-tau) were measured. Clinical and cognitive decline were examined with longitudinal CDR and cognitive composite scores (Global and Knight ADRC-Preclinical Alzheimer Cognitive Composite [Knight ADRC-PACC] Score).ResultsParticipants in the progressor and symptomatic AD groups had significantly elevated [11C]PK11195 standard uptake value ratios (SUVRs) in the hippocampus but not in the precuneus region. In the subcohort with CSF biomarkers (16 of the 24), significant negative correlations between CSF Aβ42 or Aβ42/Aβ40 and [11C]PK11195 SUVR were observed in the hippocampus and precuneus. No correlations were observed between [11C]PK11195 SUVR and CSF p-tau181 or t-tau at baseline in those regions. Higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions predicted longitudinal decline on cognitive tests.DiscussionMicroglial activation is increased in individuals with brain amyloidosis and predicts worsening cognition in AD.Classification of EvidenceThis study provides Class II evidence that in patients with AD, higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions was associated with longitudinal decline on cognitive tests.

Published
2021

116. Are Government Owned Investment Funds Created Equal? Evidence from Sovereign Wealth Fund Real Estate Acquisitions

Author

Peng Liu, S. McKay Price, and Nathan Mauck

Subjects
Economics and Econometrics, 050208 finance, business.industry, 05 social sciences, Institutional investor, Assets under management, Financial system, Real estate, Foreign direct investment, Capitalization rate, Urban Studies, Private equity, Accounting, Sovereign wealth fund, 0502 economics and business, 050207 economics, business, Finance, Financial services
Abstract

Sovereign Wealth Funds (SWFs) are an institutional investor class about which relatively little is known. Even though they have trillions of dollars in assets under management, their (typically) highly secretive nature renders them difficult to analyze in an academic context. We utilize transactional data from the Sovereign Wealth Fund Institute to provide the first academic analysis of SWF real estate investment activity of which we are aware. To better understand this growing investor class, we compare SWFs with their most closely related institutional group, public pension funds (PPFs). While both SWFs and PPFs are state owned investment funds, we find SWFs have lower Stone and Truman (2016) best practice scores (based on fund structure, governance, transparency and accountability, and behavior.) Further, while both SWFs and PPFs show increasing levels of cross-border real estate investment, SWFs are significantly more likely than PPFs to invest across international borders. We find the percentage of SWF cross-border real estate investment to be substantially higher than the percentage of SWF cross-border investment in public and private equity documented in other studies. Moreover, in a subsample of acquisitions in the U.S., cross-border real estate investments are in locations with lower capitalization rates than domestic acquisitions for both SWFs and PPFs, and there is no discernable difference in rates across the two fund types, on average.

Published
2019

118. Hepatocyte necrosis on liver allograft biopsy: Normothermic machine perfusion is the ideal platform for using these grafts in high-risk recipients

Author

Darius F. Mirza, S. McKay, Desley Neil, Mohammad Alzoubi, Hermien Hartog, M. Thamara P. R. Perera, Hanns Lembach, and Angus Hann

Subjects
Transplantation, medicine.medical_specialty, Machine perfusion, Necrosis, business.industry, Biopsy, Urology, Organ Preservation, Allografts, Transaminase, Perfusion, surgical procedures, operative, Liver, Hepatocyte necrosis, medicine, Hepatocytes, Humans, Allograft biopsy, medicine.symptom, Living donor liver transplantation, business, Contraindication
Abstract

Hepatocyte necrosis is an undesired finding on liver allograft biopsy and donor transaminases are considered surrogate markers for donor liver allograft quality. Mild to moderate elevation of donor transaminases are not a contraindication to transplantation, however severe elevation often denotes ischaemic hepatocyte necrosis and these grafts are seldom considered for transplantation.

Published
2021

119. Group-Based Trajectory Modeling of Pulmonary Function in People Living with HIV

Author

Laurence Huang, D. Reddy, D.G. Lazarous, R.F. Foronjy, K.M. Kunisaki, Heather S. McKay, Seyed Mehdi Nouraie, Ada A. Adimora, Caitlin A. Moran, S.K. Cribbs, Valentina Stosor, Igor Barjaktarevic, Meredith C. McCormack, Margaret A. Fischl, Mardge H. Cohen, M.B. Drummond, Charles R. Rinaldo, I. Konstantinidis, Rebecca S. DeSensi, Alison Morris, and Jodie Dionne-Odom

Subjects
Group based, medicine.medical_specialty, Physical medicine and rehabilitation, business.industry, Human immunodeficiency virus (HIV), Trajectory, Medicine, business, medicine.disease_cause, Pulmonary function testing
Published
2021

120. Surface science motivated by heating of trapped ions from the quantum ground state

Author

Kyle S. McKay, D. A. Hite, and David P. Pappas

Subjects
Physics, Kelvin probe force microscope, Work (thermodynamics), Condensed Matter - Materials Science, Atomic Physics (physics.atom-ph), Binding energy, General Physics and Astronomy, Materials Science (cond-mat.mtrl-sci), FOS: Physical sciences, Molecular physics, Ion, Physics - Atomic Physics, X-ray photoelectron spectroscopy, Electrode, Ground state, Noise (radio)
Abstract

For the past two and a half decades, anomalous heating of trapped ions from nearby electrode surfaces has continued to demonstrate unexpected results. Caused by electric-field noise, this heating of the ions' motional modes remains an obstacle for scalable quantum computation with trapped ions. One of the anomalous features of this electric-field noise is the reported nonmonotonic behavior in the heating rate when a trap is incrementally cleaned by ion bombardment. Motivated by this result, the present work reports on a surface analysis of a sample ion-trap electrode treated similarly with incremental doses of Ar$^+$ ion bombardment. Kelvin probe force microscopy and x-ray photoelectron spectroscopy were used to investigate how the work functions on the electrode surface vary depending on the residual contaminant coverage between each treatment. It is shown that the as-fabricated Au electrode is covered with a hydrocarbon film that is modified after the first treatment, resulting in work functions and core-level binding energies that resemble that of atomic-like carbon on Au. Changes in the spatial distribution of work functions with each treatment, combined with a suggested phenomenological coverage and surface-potential roughness dependence to the heating, appear to be related to the nonmonotonic behavior previously reported., 18 pages, 6 figures. New J. Phys. (2021)

Published
2021

121. The Dictator's Wife

Author

Hollie S McKay and Hollie S McKay

Abstract

With a childhood defined by the palm trees of Beverly Hills and the mysterious confines of Mulholland Drive, all Anna Paradis wants is to make sense of a haunting vision and an unencumbered life serving others. But when she falls in love with the second son of a Middle Eastern dictator, her fabled existence is thrown into disarray after she unexpectedly ascends to become the next Dictator's Wife and is forced to step into an unfamiliar fray. At the same time, Anna makes a chilling discovery about her upbringing: a discovery that threatens to unravel that entire iron-fisted empire and could cost her life in the pursuit of answers and accountability. Caught in the crossfire of death and destruction – and becoming the target of global condemnation herself – Anna is forced to grapple with her fallibility as a government figurehead and navigate the complex web of who can and cannot be trusted in and out of her gilded Palace bubble. As the painful secrets of her past and the ramifications of an entire life fighting a psychological war come to light, the First Lady remains bitterly determined to record her version of events before it is too late.

Published
2024

123. Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Author

John V Deighan, S.K. Sundaram, John Marshall, Trinh Duong, Abdulla Alhasso, Ruth E Langley, M. Laniado, Roger Kockelbergh, Christopher D Scrase, Jane Worlding, Alvan Pope, Stuart D. Rosen, Matthew Nankivell, Edgar Paez, Howard Kynaston, S.T Williams, Iqtedar Ahmed Muazzam, Silvia Forcat, Gerald N. Collins, Angus Robinson, Sanjay Dixit, Noel W. Clarke, Caroline Manetta, Duncan C. Gilbert, Archie Macnair, Melanie Weiss, Mahesh K. B. Parmar, S. McKay, Sanjeev Madaan, Jonathan McFarlane, and Stephen Mangar

Subjects
Male, medicine.medical_specialty, Transdermal Patch, 030204 cardiovascular system & hematology, Adenocarcinoma, Androgen suppression, Administration, Cutaneous, Article, law.invention, Gonadotropin-Releasing Hormone, Management of prostate cancer, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Adverse effect, Testosterone, Aged, Ischemic Stroke, Aged, 80 and over, Heart Failure, Embolic Stroke, Estradiol, business.industry, Hazard ratio, Prostatic Neoplasms, Androgen Antagonists, Estrogens, General Medicine, Middle Aged, medicine.disease, United Kingdom, Clinical trial, Androgens, Gynecomastia, Thrombotic Stroke, business
Abstract

BACKGROUND: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. METHODS: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. FINDINGS: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p

Published
2021

124. Measurement of electric-field noise from interchangeable samples with a trapped-ion sensor

Author

Andrew C. Wilson, Shlomi Kotler, Philip D. Kent, Dietrich Leibfried, David P. Pappas, Kyle S. McKay, Daniel H. Slichter, and D. A. Hite

Subjects
Physics, Condensed Matter::Quantum Gases, Atomic Physics (physics.atom-ph), business.industry, Computation, Measure (physics), FOS: Physical sciences, Ion, Characterization (materials science), Physics - Atomic Physics, Optics, Physics::Plasma Physics, Electric field, Electrode, business, Quantum, Noise (radio)
Abstract

We demonstrate the use of a single trapped ion as a sensor to probe electric-field noise from interchangeable test surfaces. As proof of principle, we measure the magnitude and distance dependence of electric-field noise from two ion-trap-like samples with patterned Au electrodes. This trapped-ion sensor could be combined with other surface characterization tools to help elucidate the mechanisms that give rise to electric-field noise from ion-trap surfaces. Such noise presents a significant hurdle for performing large-scale trapped-ion quantum computations., 11 pages, 4 figures

Published
2021

125. Contributors

Author

James Berry, Edward P. Clapp, Lauren E. Coursey, Kyle J. Emich, Colin M. Fisher, Vlad Petre Glaveanu, Inga J. Hoever, James C. Kaufman, Jared B. Kenworthy, Natalia Korchagina, Jan Kratzer, Li Lu, Charalampos Mainemelis, Alexander S. McKay, Matthias Mrożewski, Ingunn Johanne Ness, Paul B. Paulus, Alexander Pundt, Ludvig Johan Torp Rasmussen, Roni Reiter-Palmon, Janice Sanchez, Joel T. Schmidt, Min Tang, Daan van Knippenberg, and Wen-Xin Xie

Published
2021

126. BJS commission on surgery and perioperative care post-COVID-19

Author

E. Abahuje, A. Abbas, M. Abd El Aziz Abd El Maksoud, A. Abdelhady, S. Abdelhamid, H. Abdelkarem Ahmed Faraj, B. Abdelqader, T. Abdelrahman, H. Abdou, A. Abdullah, M. Abedua Harrison, E. Abem Owusu, A. Aboalazayem, R. Aboulhosn, S. Abu Oda, A. Abubakar, A. Abutaka, D. Acevedo Fontalvo, S. Acuna, A. Adefemi, S. Adegbola, T. Adenuga, A. Adeyeye, A. Adil Hilmi, A. Adisa, K. Aditya, T. Adjeso, R. Aftab, A. Afzal, V. Aggarwal, A. Aggarwal, R. Aguilera, M. -L. Aguilera-Are´valo, E. J. Aguirre Salamanca, I. Aguirre-Allende, D. Ahari, H. Ahmad, F. Ahmad Rauf, A. Ahmad Zartasht Khan, S. Ahmed, N. Ahmed Fieturi, S. Ahmed Mohamed, Z. Ahmed-Bakhsh, M. Ahsan Javed, L. Akano, A. Akbar, M. Akhbari, P. Akhmedov, G. Aksit, Y. Akula, A. S. Alagaratnam, S. Al Majid, O. Al Mukhtar, H. Al Omran, N. AlAsali, M. Al-Azzawi, R. Al-Habsi, H. Al-Iraqi, H. Al-Naggar, E. Alameer, H. Albirnawi, D. Alderson, F. Aldulaijan, R. Alejandro Miranda Ojeda, A. AlHasan, S. Ali, A. Ali, M. Ali Khan, Y. Alimova, F. Aljanadi, R. Aljubure, N. Allopi, H. Almedbal, M. Almubarak, Z. Alqaidoom, N. Alselaim, M. Alshaar, R. Alshammari, K. Altaf, S. Altıner, B. Altunpak, L. A. Alvarez Lozada, E. Amal Nahal, A. Amer, K. Amin, U. Aminu, N. Amisi Numbi, T. Amjad, R. Amoah, Y. An, N. -A. Anastasopoulos, J. Andre´s Urrutia, F. Angarita, K. -L. Angarita, M. A´ ngel FreirI´a Eiras, A. Antypas, M. A. Anwar, H. Anwar, T. O. Apampa, K. Apostolou, C. Aquina, R. Arachchige Adithi Himika Randeni, M. I. Archila Godı´nez, O. Arez, A. A. Arezzo, P. Armonis, S. Arshad, M. Arshad Salman, A. Arshid, P. C. Arteaga Asensio, T. Arthur, A. Arumuga Jothi, F. Aryo Damara, L. Asensio Gomez, J. Ashcroft, S. Ashraf, A. Asif, M. Atif, M. Attaullah Khan, N. Avellaneda, S. Awad, M. Awadh, A. Axiaq, A. Ayad Mohammed Shuwayyah, D. Ayalew, E. Aytac, F. Azam, J. Azevedo, B. Azhar, J. Aziz, A. Aziz, A. Azzam, A. Baba Ndajiwo, M. Baig, D. Baker, F. Bakko, R. Balachandran, G. Balachandran, J. Balagizi Mudekereza, E. Balai, B. Balci, A. Balduzzi, A. Balhareth, S. Bandyopadhyay, D. Banerjee, D. Bangalore Mahalinga, B. Bankhead-Kendall, N. D. A. Bankole, V. Banwell, F. Baris Bengur, B. Baris Ozmen, M. Barnard, R. Barnett, J. A. Barreras Espinoza, A. Barrios, G. Bass, M. Bass, A. Bausys, A. Bavikatte, J. Bayram, M. Belousov, A. G. Berardi, A. Beamish, C. Beattie, F. Belia, V. Bellato, S. Bellikatti, S. Benjamens, C. Benlice, S. Bennedsgaard, S. Bennett, Z. Bentounsi, H. Bergenfeldt, A. Bergenfelz, M. Besselink, G. Bhandoria, E. Bhangu, M. Bhatia, M. T. Bhatti, Z. Bilgili, G. Bislenghi, C. Bisset, S. Biswas, J. Blake, R. Blanco, L. Boccalatte, R. Boden, C. Bojanic, M. Boland, P. Boland, E. Bollen, E. -A. Bonci, L. Boni, A. Booth, R. Booth, A. Borakati, G. E. Borunda Escudero, S. J. Bosco, P. Bostro¨ m, P. Botelho de Alencar Ferreira Cruz, K. Bouchagier, A. Bouhuwaish, M. Boutros, K. Boyce, C. Boyle, L. Bradshaw, A. Brandl, A. Brar, G. Brat, H. Brenkman, C. Brennan, C. Brines, A. Brookmyre, C. Brosnan, L. Brouwers, A. Brown, L. Brown, C. Brown, J. Brown, V. BS, M. Buksh, M. Bunani Emmanuel, D. Burbano, A. Burelli, A. Burke, J. Burke, N. Burlov, A. Burns, O. Burton, A. Butt, B. Buzra Ozkan, L. Cabrera Silva, E. Y. Caicedo, T. Calderbank, W. Cambridge, G. Campelo, O. Can Tatar, F. Carbone, F. Carrano, D. Casallas, D. Casanova Portoles, F. Casciani, I. Cassimjee, O. A. Castaneda Ramı´rez, V. Catala´ n, J. Caviedes, L. Cayetano, M. ~ Ceresoli, M. Chan, V. Chan, P. Chandrasinghe, S. Chapman, A. Chaturvedi, D. Chaudhry, H. Chaudry, H. W. Chen, A. Cheng, M. Chernykh, A. M. Cherrie, I. Cheruiyot, J. Cheung, C. Chia, J. Chica, N. Chinai, A. Chirwa, J. Chiwaligo, A. Choi, J. Choi, M. R. Chowdhury, E. Christopher, N. Christou, T. Chu, D. Chua, H. W. Chua, C. Chung, A. Cihat Yildirim, M. Cillo, S. Cioffi, H. Claireaux, S. Clermonts, R. Clifford, M. Climent, A. Clynch, R. -J. Coelen, E. Cola´ s-Ruiz, A. Collar, M. Collard, K. C. Conlon, T. Connelly, K. Connor, J. A. Cook, T. Correia de Sa´, N. Cos¸gun Acar, T. Costa, D. Couch, S. Cowper, B. Creavin, B. Crook, A. Curell, R. D’alessio, J. Dale, J. Damgaard Eriksen, I. Dario Martin Gonzalez, A. Darwish, M. Das, R. Das, K. Das, R. Dave, S. O. David, T. Davies, C. Davis, S. Davison, V. Davletshina, A. Dawidziuk, A. Dawson, M. de Andres Crespo, H. de Berker, P. de Dieu Ngo, E. Dekker, R. de la Caridad Espinosa Luis, B. de Lacy, N. Demartines, A. de Montserrat Medina Sifuentes, S. De Silva, C. del Rio, V. Delaune, A. Dell, I. Demirbas¸, S. Demirli Atici, M. Deniz Tepe, M. Derebey, G. Desai, M. Desai, S. Devarakonda, N. Deveras, G. Di Franco, M. Di Martino, F. Di Marzo, A´ . Dı´az, G. Diaz del Gobbo, C. DiazCastrillon, L. Dick, K. Dickinson, E. Diego, I. Dimasi, A. Ding, S. Dingemans, L. Dixon, B. Dixon, W. Doherty, D. Dooreemeah, C. Donohue, M. Dornseifer, F. Dossa, W. Dossou, T. Drake, I. Drami, G. Drevin, M. C. du Plessis, N. Dudi-Venkata, R. Dudley, S. Duffy, D. Duklas, B. -D. Dumbrava, F. Duygu Avlar, A. Dworzynska, W. Ebrahim, A. Ebrahim, E. Efre´n Lozada Herna´ ndez, N. Ehigie, M. El Boghdady, C. El Hasnaoui, M. El Sheikh, A. El-Hussuna, O. Eldurssi, H. Elfeki, M. Elhadi, M. Elhassan, A. Elhissi, B. Elliot, C. Elsenbroek, B. Elsolh, N. Elson, H. Eltyeb, H. Emerson, S. H. Emile, G. Endalle, W. English, C. Ercisli, G. Espinosa, M. Essam Abdelraheem, H. Essangri, P. Etienne, M. D. Evans, T. Evans, C. Ezeme, F. Ezzahraa, T. Fadalla, J. Fagan, M. Fahmy, C. Fairfield, O. Falade, S. Famularo, F. Faqar-Uz-Zaman, Y. Farid, A. Farooq, H. Farooq, F. Farooqui, B. Farquharson, A. Faruqi, R. Faulder, M. Faut, K. Fechner, T. Feenstra, M. Fehervari, L. Fernandez, J. Ferna´ ndez Alberti, L. Ferrario, D. Field, L. Fiore, S. Fingerhut, S. Finlayson, N. Fleming, C. Fleming, E. Florial, M. Fok, D. Fokin, M. Foley, M. P. Forero, T. Forgan, M. Fornasiero, H. Fowler, G. Fowler, E. Franchi, L. Franklin, A˚ . Fredriksson, P. Fruhling, G. Fuentes Navarrette, A. Fu¨ lo¨ p, M. Furtado, T. Gaarder, N. Galbraith, I. T. K. Gallagher, G. Gallo, T. Gana, E. Gaskin, M. Gasparini, R. G. Gatan, E. Geary, K. Gelaye Wudineh, G. Gemenetzis, M. Georgi, H. Ghalige, W. Ghareeb, T. Ghatwary Tantawy, C. Ghomsi, A. Ghuman, P. Giannakis, F. Giron, K. Gjengedal, E. Gkotsis, J. Glasbey, S. Godahewa, D. Godula, P. Goffredo, S. Goh, M. Golriz, L. Gomez, D. Gomez Gomez, R. Gonzalez, D. Gonzalez, E. Gonzalez Gutierrez, D. Gopar, L. Gordini, A. Gori, S. Gorta´ zar, N. Gousy, R. Gowda, M. Gowda, J. Gqada, M. Grechenig, J. Greer, L. Grego´ rio, A. Grigorova, H. Grimes, V. Groot, R. C. Grossman, R. Gruber, A. Gru¨ ter, R. Guest, R. Gujjuri, E. Gu¨ lc¸ek, B. Gulcu, K. Gull, M. Gulmez, V. Gupta, A. Gutlic, T. Guven, T. Gwatirisa, G. Gwini, P. Gwodog, S. Gysling, M. Habib, A. B. Hafeez Bhatti, J. Hallesmith, S. Halloran, M. Hamza Sadiq, C. Haney, N. Hanna, L. Hanna, M. Hannington, J. Harbjerg, D. Haribaskaran, N. Harran, B. Harrington, E. Harrison, R. Hasan, S. Hashmi, M. Hassan, A. Hassan, L. Haverkamp, S. Hazen, B. Heer, J. Heil, J. Helliwell, N. Henriksen, D. Henshall, M. Hermanson, S. Hermena, D. Hettiarachchi, C. Hextall, M. Hidalgo, H. Hidayat, A. Hider, P. Higgins, R. Hinchliffe, D. Hirani, D. Hirpara, I. Hisham, M. Hite, S. M. Hoh, C. Holmberg, E. Ho¨ lmich, F. Holst, A. Hossam, A. Hossam Elfallal, P. Howard, E. Huaman, Y. Huang, L. Huang, D. Huang, T. Huber, J. Hugh, J. Hughes, F. Hu¨ ttner, R. Huynh, A. Hylands, J. Iannuzzi, B. Ielpo, A. Iftikhar Talib, J. Ignacio, P. Ignatavicius, S. Ike, C. Ikwu, M. Inama, A. Ing, A. Ingels, A. Isik, N. Islam, I. J. Ives, A. J. M. S. AlHasan, C. J. Perez Rivera, F. Ja´ come, T. Jaffer, O. Jagiella-Lodise, M. Jain, K. Jain, M. Jakubauskas, M. Jalal, H. James, Y. Jang, B. Janssen, H. Jansson, U´ . Jariod-Ferrer, H. Javanmard, S. Javed, U. Jayarajah, I. Jayasuriya, J. Je, Z. Jessop, E. Jia Lin Tang, H. Jiang, Y. Jiayan, T. Jih Huei, R. Jimenez-Rodriguez, D. Joh, A. Johnson, N. Jones, C. Jones, C. Jordan, J. Jose´ Nu´ nez Ju, ~ M. Jose´ Pizarro, C. Jose Salazar J. Joseph, C. Justiniano, T. Kabir, M. Kadhum, C. Kalfountzos, E. Kalogiannaki, K. Kalyanasundaram, S. Kamarajah, M. Kamil Quraishi, Y. Kanemitsu, A. Kapila, V. Kapila, G. Karagiannidis, M. Kashif, S. Kathiravelupillai, A. Kathiravelupillai, E. Katsogridakis, K. Kaur, H. Kaur Sekhon Inderjit Singh, N. Kausur, M. Kawka, G. Keehan, S. Kehlet Watt, M. Kelly, M. E. Kelly, I. Kelvin Egbuchulem, G. Kembuan, E. Khajeh, A. Khaled Elfaitur, M. F. Khan, S. Khan, M. Khan, D. Khan, H. Khan, H. Khatkar, E. Khatkov, R. Khaw, B. Kim, K. Kishore Siddiraju, D. Kitua, B. Kırımtay, S. Kmezic, S. Knight, T. Koe¨ter, A. Koh, F. Koh Hong Xiang, T. Kojo Anyomih, A. I. N. Kok, R. Kokelaar, I. Koliarakis, S. Kolli, J. Kong, D. Ko¨ nig, M. otze, A. Kourdouli, M. Kowal, A. Kraima, F. Kramer, M. Kryzauskas, I. Kuchynskyi, C. Kuemmerli, S. Kuiper, S. Kumar, A. Kumar, L. Kumar, H. Kumar, N. Kumar, S. Kumar Bandyopadhyay, P. Kumar Garg, S. Kumar Venkatappa, J. Kung, S. Kural, A. Kushairi, E. Kuuzie, M. Kvietkauskas, I. Kwek, J. La, L. Lai, S. Lakpriya, K. Lam, M. Lami, I. Lansdorp-Vogelaar, P. Lapolla, H. Larsen, J. Latif, U. Laudari, A. Laurnezi, A. Lawal, S. Lawday, H. Lederhuber, A. Lednev, R. Lee, M. E. van Leerdam, G. Lefevbre, M. Lesmus, F. A. Leyva Moraga, E. Leyva Moraga, F. Leyva Moraga, H. L. Li, A. Li, Z. Li, E. Licardie, A. Light, A. L. Lightner, A. Lin, E. Lincango, F. Litta, H. Liu, B. Lofthouse, M. A. Londono, R. Lopes, R. Lopes de Freitas, L. Lopez, A. I. Lo´ pez, J. ~ Lopez-Gomez, G. Lopez-Pena, R. Lowe, D. Lowe, M. Lowey, G. Loy, V. Lozanovski, J. Luzon, P. Lynn, T. Maccabe, A. Machielsen, C. A. Mafla Herrerı´a, L. Maggino, K. Mahawar, D. Mahmood, M. Mahmoud, K. Mahtani, I. Maitra, S. Maji, I. Majiet, L. Mal, J. Malherbe, K. Malhotra, P. Malkomes, E. Man, A. Manan Sheikh, S. Manjunath, R. Manzano Nunez, S. Manzoor, R. Maqsood, G. ~ Marchegiani, F. Marchegiani, D. Marı´n, A. Marin, I. Marks, E. Marson, A. Martensen, D. Martin, G. Martı´n Martı´n, B. Martin-Perez, P. Martinez, P. Marwaha, C. Mashauri, H. Mashbari, Ł. Masior, R. Masri, L. Masud, S. Masudi, G. Mateu Calabuig, S. Math, A. Matrachisia, J. Mayol, D. Mazingi, A. Mazzotta, J. McAlinden, G. McCabe, L. McColm, H. McElvaney, K. McGivern, J. McGovern, E. McGuinness, N. McInerney, S. Mckay, C. McKee, M. McKenna, N. McKenna, K. McLean, S. Mediratta, Y. Medkova, O. Medzhidov, A. Mehraj, M. Mekhael, O. Mekinde, C. Mellenthin, A. Melucci, K. Mentor, J. Merchant, H. Messias, M. Messeha, C. Meza, P. Mhango, M. Miladinov, M. Milagros Niquen Jimenez, P. Miller, E. Mills, A. Milton, O. A. Minayeva, Z. MinHua Zheng, H. Mischlinger, B. Mo¨ ckli, R. Modi, H. M. Mohamed, M. Mohamed, T. Mohamed Abulghasm, S. A. Mohammad, T. O. Mohammed, A. Mohammed, H. Mohan, M. Mohan, I. Moin, V. Mok, G. Molina, J. Moloney, J. Moneim, M. Monfort Mira, B. Montcusı´ Ventura, M. Montouri, M. Moossdorff, I. Mora-Guzma´ n, B. Moran, R. A. R. Mora´ n, S. Moreno-Ordaz, A´ . Morera, R. Morgan, R. Morley, D. Moro-Valdezate, S. Moros, J. -L. Moss, A. Morven, D. Morton, A. Moynihan, M. Moyo´ n, N. Muduli, N. Mugla, W. Mugla, P. Mu¨ ller, G. Mun, R. Mundhada, I. Munir, F. Munoz, E. Mu ~ noz, A. Mu ~ noz, D. ~ C. Munoz Balderas, E. Murgitroyd, V. Murray, S. Murthy, W. ~ Mushiwokufa, H. Mustafa, B. Mustakimov, P. Mutambanengwe, P. Myint, S. Nadkarni, P. A. Naess, S. Nahar, P. Naidoo, R. Nam, S. Nandhra, N. Nanjappa, V. Narasimhan, W. Nardi, M. Nasir, A. Naughton, D. Naumann, S. Navarro, M. Nawaaz Karimbocus, A. Nazir, S. Ndereya, A. Ndong, I. Negoi, D. Nel, D. Nelson, S. Nepal, T. Nugent, D. Nepogodiev, J. Neufeld, J. Ng, D. Ng, C. E. Ng, S. Ngaserin, L. Ngu, E. Ngwenya, R. N. Fhearaigh, T. -K. Nikolousakis, M. Ninkovic, G. Nita, C. Nitschke, E. Noren, T. Noton, A. Novikova, Z. Nowinka, T. Nyakunengwa, A. Nyalundja, I. Nzenwa, H. Ø Kristensen, C. O’Brien, L. O’Brien, S. O’Brien, J. O’Reilly, S. O’Rourke, M. O’Sullivan, M. O’Dwyer, L. Ochieng, E. Oderoha, K. E. Oh, L. O¨ hlberger, M. O¨ lc¸u¨ m, A. Olkina, M. Omkumar, B. Omnitel, D. Oncel Yakar, K. Ong, L. Ong Wei Lin, R. Ooi, S. Ooi, A. Oomman, D. Oon Tyjet, S. Opiyo, J. J. Oscullo Yepez, N. Osei-kuffour, T. Osunronbi, A. Ottlaka´ n, S. Oussama Kacimi, S. Ovaere, A. Ozair, F. Pachler, S. Pai Oo, S. Paiella, L. Panaiotti, N. Panda, S. Pandarinath, D. Pandey, S. Pandrowala, F. Papa Mamadou, M. Paranathala, J. Park, C. Parmar, A. Parvez, L. Pasovic, A. Pasquer, N. Pasumarthy, F. Pata, T. Patel, P. Patel, N. Patel, M. Patel, N. Patron Uriburu, R. Patrone, A. Paul, O. M. Pavan Kumar, A. Pavithran, M. Pedraza Ciro, G. Pellino, A. Peloso, M. T. Pena~ Gallardo, A. Pena Velazquez, J. Perea, L. E. Pe´rez-Sa´ nchez, T. ~ Perra, G. Perrotta, P. Petersson, G. Petra, N. Petrucciani, C. Pickin, V. Pino, E. Pinotti, F. Pinto, P. Plum, F. Podesta, T. Pollini, M. Pompeu Sa´, F. Ponce Leon, H. S. Ponniah, X. Ponte de Sousa, J. Ponton, A. Pontula, M. Popa, A. L. Portilla, F. Posner, S. Post, A. Potolicchio, S. Pouwels, A. Povo, P. Prasad, S. Preciado, R. Preece, D. Proud, J. A. Pulido Segura, N. Puliyath, M. Qui, A. S. Quimbaya Rodrı´guez, W. Raby-Smith, A. Racovit¸a, A. Rad, R. Radwan, M. Rafaih Iqbal, A. Rafik, B. Raguan, M. Rahi, J. -L. Rahiri, J. Rahme, L. Rai, A. Raj, A. Raj Saksena, M. Raja, J. Ramirez, J. Ramzi, J. Ranstam, C. Rao, A. Rashid, B. Ratnayake, K. Rattanasirivilai, K. Raubenheimer, N. Ravikumar, S. Ravn, N. Razoz, W. Rea, A. Regan, M. Rela, A. Remme, C. E. Rey Chaves, A. Reyes, A. Riad, D. Rice, K. Rios Quintana, A. Ritter, M. Roalsø, D. Robinson, J. Rodriguez, F. Rodrı´guez, M. C. Rodriguez, A. Rogers, J. Rohila, D. Romanyuc, I. Romic, M. Rommaneh, G. Rompianesi, F. Rosa, F. Roscio, A. Rose, T. Rotimi, H. Ruiz, J. Ruiz Yucuma, E. Ruiz-U´ car, M. Ruslan, M. Rutega˚ rd, E. Ryan Harper, A. Ryckx, D. Rydbeck, E. Fonseca, A. Sanchez Teran, S. Sanchez Ussa, O. Sandli, H. Sanfey, J. Sanghera, I. Sani, M. Santafe Guerrero, M. Sante Fornasiero, O. Santes Jasso, I. Santos Pereira, H. Santos Sousa, A. Saratzis, A. Sarmiento Alarcon, T. Saumtally, R. Sayyed, M. Schettino, L. Schleimer, T. Schmidt, K. Schondffelt, M. Schwab, A. Scott, H. Searle, L. Sebopelo, B. Seeglier, R. Seishima, D. Semenvov, A. Senent-Boza, J. Sepulveda, M. Serenari, M. Serrano Navidad, I. Sert, E. Sewart, A. Sgro`, V. Shadrina, K. Shah, F. Shahid, M. Shalaby, B. Shankar, J. Shapiro, L. Sharma, A. Sheel, A. Shenfine, S. Shenoy, A. Sherif, N. Shetty, R. Shetty, T. C. Sia, D. Sichimba, H. Siddique, I. Siddiqui, G. Simkens, J. Simoe, H. Simon, L. Sinan, T. Singh, K. Singh, Y. Singh, L. Sinha, L. Siragusa, T. Sluckin, Y. W. Smart, H. Smith, K. Smith, L. Smits, C. Sneep-van Kessel, C. Sohrabi, O. Solo´ rzano Pineda, A. Soma, L. Sooriyapiragasam, K. Søreide, M. Sparavigna, R. Spence, N. Spencer, H. Spiers, A. Spinelli, J. Sprakel, S. Sravanam, M. Srinivasan, R. Srinivasan, A. Staniszewska, S. J. Stanworth, K. Stasinos, R. J. C. Steele, I. Steinholt, M. Steinruecke, B. -J. Stephen, J. Stijns, M. Still, W. Stupalkowska, S. Subba, V. V. Subbotin, P. Sucharitkul, A. 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Ravikumar, N, Ravn, S, Razoz, N, Rea, W, Regan, A, Rela, M, Remme, A, Rey Chaves, C, Reyes, A, Riad, A, Rice, D, Rios Quintana, K, Ritter, A, Roalso, M, Robinson, D, Rodriguez, J, Rodriguez, F, Rodriguez, M, Rogers, A, Rohila, J, Romanyuc, D, Romic, I, Rommaneh, M, Rompianesi, G, Rosa, F, Roscio, F, Rose, A, Rotimi, T, Ruiz, H, Ruiz Yucuma, J, Ruiz-Ucar, E, Ruslan, M, Rutegard, M, Ryan Harper, E, Ryckx, A, Rydbeck, D, Sa-Marta, E, Sadien, I, Safari Nteranya, D, Sagoo, K, Sakata, S, Saladino, E, Saleem, A, Saleem, S, Salehi, M, Salih, S, Sallinen, V, Salvans, S, Sam, Z, Samadov, E, Sampaio Alves, M, Sanad, A, Sanchez Fonseca, S, Sanchez Teran, A, Sanchez Ussa, S, Sandli, O, Sanfey, H, Sanghera, J, Sani, I, Santafe Guerrero, M, Sante Fornasiero, M, Santes Jasso, O, Santos Pereira, I, Santos Sousa, H, Saratzis, A, Sarmiento Alarcon, A, Saumtally, T, Sayyed, R, Schettino, M, Schleimer, L, Schmidt, T, Schondffelt, K, Schwab, M, Scott, A, Searle, H, Sebopelo, L, Seeglier, B, Seishima, R, Semenvov, D, Senent-Boza, A, Sepulveda, J, Serenari, M, Serrano Navidad, M, Sert, I, Sewart, E, Sgro, A, Shadrina, V, Shah, K, Shahid, F, Shalaby, M, Shankar, B, Shapiro, J, Sharma, L, Sheel, A, Shenfine, A, Shenoy, S, Sherif, A, Shetty, N, Shetty, R, Sia, T, Sichimba, D, Siddique, H, Siddiqui, I, Simkens, G, Simoe, J, Simon, H, Sinan, L, Singh, T, Singh, K, Singh, Y, Sinha, L, Siragusa, L, Sluckin, T, Smart, Y, Smith, H, Smith, K, Smits, L, Sneep-Van Kessel, C, Sohrabi, C, Solorzano Pineda, O, Soma, A, Sooriyapiragasam, L, Soreide, K, Sparavigna, M, Spence, R, Spencer, N, Spiers, H, Spinelli, A, Sprakel, J, Sravanam, S, Srinivasan, M, Srinivasan, R, Staniszewska, A, Stanworth, S, Stasinos, K, Steele, R, Steinholt, I, Steinruecke, M, Stephen, B, Stijns, J, Still, M, Stupalkowska, W, Subba, S, Subbotin, V, Sucharitkul, P, Sudarsanam, A, Sudhamsh Reddy, D, Suhardja, T, Suliman, M, Sund, M, Sunilkumar, A, Suresh, N, Sussmes, S, Sutton, P, Syltern, J, Taha, A, Takamizawa, Y, Takoutsing Dongmo, A, Tamas, T, Tan, L, Tan, J, Tan, K, Tan, E, Tan Yong Hui, A, Tanase, A, Tariverdiev, A, Tasnem, A, Tatar, C, Tay, E, Tejedor, P, Tesfaye, G, Tetinou, F, Thorpe, C, Thyo, A, Tlelo Amastal, D, Tolani, M, Tolga Saracoglu, K, Tolgyes, T, Tong, J, Torrent Jansa, L, Toscano Igartua, S, Tovani Palone, M, Traff, H, Trevis, J, Tummers, W, Tur, A, Turchenko, I, Uche, V, Uddin, A, Udonsak, N, Ullah, M, Urbonas, T, Uwins, C, Uy Magadia, E, Uzair Qureshi, A, Uzun, K, Vadim, P, Valarche, G, Valdez Gonzalez, R, Vallee, M, Van Beek, D, Van Dalen, A, Van Den Hondel, D, Van Der Stok, E, Van Dorp, M, Van Oostendorp, S, Van Praag, E, Van Rees, J, Van Silfhout, L, Varga, Z, Varghese, S, Varghese, C, Varghese, J, Vasilica, A, Vasquez Ojeda, X, Vega, E, Vehler, S, Venchiarutti, R, Vengatesan, S, Venn, M, Verma, D, Vianey Partida Nava, G, Victoria, D, Vieira, P, Vilar Alvarez, M, Vinci, D, Viscasillas Pallas, G, Viswanath, M, Vivanco, J, Vizcaya Rodriguez, V, Vo, J, Volchanski, D, Voron, T, Voronovskyi, Y, Vu, J, Wadhwa, M, Wadhwa, S, Wagner, G, Wallace, M, Wang, Y, Wang, J, Wani, A, Wanigasooriya, K, Wanjara, S, Wanjiku, N, Warner, C, Wei Leow, T, Weiser, T, Weisters, M, Wellington, M, Wells, C, Wenzelberg, C, Wettstein, D, Wezel, A, Wheldon, L, Widmer, L, Wilson, M, Wigmore, S, Wijayaratne, T, Wijeyaratne, M, Wijnhoven, B, Wilkin, R, Williams, E, Willis, F, Winter, D, Wirsik, M, Wishah, B, Wong, G, Wong, W, Wong, K, Worku, D, Wright, E, Wright, J, Wroe Wright, O, Xenacki, S, Xia, W, Xu, W, Xu, Z, Yalcinkaya, A, Yang, W, Yang, P, Yanishev, A, Yanzon De La Torre, A, Yao, H, Yaqoob, E, Yen Ling Quake, S, Yeo, D, Yeom, B, Yershov, D, Yiasemidou, M, Yildiz, A, Yiu, A, Yoav, M, Yong, E, Yoshimura, R, Younis, M, Younis Ringshawl, Z, Youssef, M, Yue, Y, Yuen, S, Yuldashev, R, Yurttas, C, Yves, B, Zaborowski, A, Zackeri, R, Zafar, A, Zahra, W, Zaidi, A, Zainudin, S, Zakeri, R, Zamora, I, Zamora, A, Zawistowski, M, Zbikowska, G, Zegers, W, Zehra, S, Zeyra, A, Zhagniyev, Z, Zhukova, L, Zivanovic, M, Zmuc, J, Zope, M, Zubayraeva, A, Zucker, B, Aguilera-Arévalo, M -L, Aguirre Salamanca, E J, Al-Asali, N, Altıner, S, Alvarez Lozada, L A, Anastasopoulos, N -A, Andrés Urrutia, J, Angarita, K -L, Ángel FreirÍa Eiras, M, Anwar, M A, Apampa, T O, Archila Godínez, M I, Arteaga Asensio, P C, Bankole, N D A, Barreras Espinoza, J A, Bhatti, M T, Bonci, E -A, Borunda Escudero, G E, Bosco, S J, Boström, P, Botelho de Alencar Ferreira Cruz, P, Caicedo, E Y, Castañeda Ramírez, O A, Catalán, V, Chen, H W, Chowdhury, M R, Chua, H W, Coelen, R -J, Colás-Ruiz, E, Correia de Sá, T, Coşgun Acar, N, D’Alessio, R, David, S O, de Andres Crespo, M, de Berker, H, de Dieu Ngo, P, de la Caridad Espinosa Luis, R, de Lacy, B, de Montserrat Medina Sifuentes, A, del Rio, C, Demirbaş, I, Díaz, Á, Diaz del Gobbo, G, Diaz-Castrillon, C, du Plessis, M C, Dumbrava, B -D, Efrén Lozada Hernández, E, Fernández Alberti, J, Forero, M P, Fredriksson, Å, Fülöp, A, Gatan, R G, Gortázar, S, Gregório, L, Grüter, A, Gülçek, E, Hafeez Bhatti, A B, Hoh, S M, Hölmich, E, Hüttner, F, Alhasan, A J M S, Perez Rivera, C J, Jácome, F, Jariod-Ferrer, Ú, José, J, José Núñez Ju, J, José Pizarro, M, Khan, M F, Kırımtay, B, Kmezić, S, Koëter, T, König, D, Leyva Moraga, F A, Li, H L, Londoño, M A, Lopes de Freitas, R, López, A I, Mafla Herrería, C A, Manzano Nuñez, R, Marín, D, Martín Martín, G, Masior, Ł, Möckli, B, Mohamed, H M, Mohammad, S A, Mohammed, T O, Montcusí Ventura, B, Mora-Guzmán, I, Morán, R A R, Morera, Á, Moss, J -L, Moyón, M, Müller, P, Muñoz, F, Muñoz, E, Muñoz, A, Muñoz Balderas, D C, Ng, C E, Fhearaigh, R N, Nikolousakis, T -K, Kristensen, H Ø, O’Brien, L, O’Brien, S, O’Reilly, J, O’Rourke, S, O’Sullivan, M, O’Dwyer, M, Oh, K E, Öhlberger, L, Ölçüm, M, Oscullo Yepez, J J, Osei-kuffour, N, Ottlakán, A, Pavan Kumar, O M, Peña Gallardo, M T, Peña Velazquez, A, Pérez-Sánchez, L E, Pompeu Sá, M, Ponniah, H S, Ponte de Sousa, X, Portilla, A L, Pulido Segura, J A, Quimbaya Rodríguez, A S, Racoviţă, A, Rahiri, J -L, Rey Chaves, C E, Roalsø, M, Rodríguez, F, Rodriguez, M C, Ruiz-Úcar, E, Rutegård, M, Sá-Marta, E, Sam, Z H, Emile, Sameh H, Sánchez Fonseca, S, Sgrò, A, Sia, T C, Smart, Y W, Sneep-van Kessel, C, Solórzano Pineda, O, Stephen, B -J, Takoutsing Dongmo, A B, Tamás, T, Tan, J L, Thyø, A, Tölgyes, T, Torrent Jansà, L, Tovani Palone, M R, Valdez Gonzalez, R A, van Beek, D -J, van Dalen, A S, van den Hondel, D, van der stok, E, van Dorp, M, van Oostendorp, S, van Praag, E, van Rees, J, van Silfhout, L, Vasilica, A -M, Vásquez Ojeda, X, Vilar Alvarez, M E, Viscasillas Pallàs, G, Vizcaya Rodríguez, V, Wang, Y Y, Wellington, M J, Wirsik, M M, Wong, W J, Wong, K -Y, Wright, O Wroe, Yang, P -C, Yanzon de la Torre, A, Younis, M U, Zamora, A T, and Surgery

Subjects
Adult, Male, medicine.medical_specialty, Biomedical Research, Coronavirus disease 2019 (COVID-19), International Cooperation, Practice Patterns, Commission, Global Health, Health Services Accessibility, Perioperative Care, Education, Surgeon, COVID-19, surgery, perioperative care, Medical, Pandemic, Humans, Medicine, Practice Patterns, Physicians', Graduate, Pandemics, Surgeons, Health Resource, Infection Control, Physicians', Surgical Procedures, business.industry, General surgery, Middle Aged, Operative, Education, Medical, Graduate, Surgical Procedures, Operative, Perioperative care, Health Resources, Surgery, Female, business, Human
Abstract

Background Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues’ experiences and published evidence. Methods In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. Results BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. Conclusion The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era.

Published
2021

127. An interdisciplinary view on team creativity: Toward integration across fields

Author

James C. Kaufman, Roni Reiter-Palmon, and Alexander S. McKay

Subjects
Entrepreneurship, Bridging (networking), ComputingMilieux_THECOMPUTINGPROFESSION, Edited volume, Research areas, media_common.quotation_subject, Engineering ethics, Sociology, Creativity, media_common
Abstract

This edited volume provides views and perspectives of researchers studying creativity from various social scientific areas including education, psychology, management, and entrepreneurship. This chapter concludes the book and provides an integrative view of team creativity by bridging the different research areas and chapters.

Published
2021

130. Investigating whether fractional anisotropy is associated with reduced reaction time cost on an attentional control task

Author

Qing Wang, Nicole S. McKay, John C. Morris, Tammie L.S. Benzinger, Brian A. Gordon, David A. Balota, and Jeremy F. Strain

Subjects
Epidemiology, Computer science, Health Policy, Attentional control, Time cost, Task (project management), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Modal, Developmental Neuroscience, Neuroimaging, Fractional anisotropy, Neurology (clinical), Geriatrics and Gerontology, Cognitive psychology
Published
2020

131. Longitudinal change in cortical thickness and hippocampal volume predicts cognitive decline

Author

John C. Morris, Sarah Keefe, Brian A. Gordon, Pamela LaMontagne, Aylin Dincer, Tammie L.S. Benzinger, Jingxia Liu, Nicole S. McKay, Gengsheng Chen, Lauren N. Koenig, Jason Hassenstab, and Stephanie A. Schultz

Subjects
Change over time, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Hippocampal volume, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Neuroscience
Published
2020

133. A role for myocilin in receptor-mediated endocytosis.

Author

Brian S McKay, Nicole R Congrove, Adiv A Johnson, W Michael Dismuke, Trent J Bowen, and W Daniel Stamer

Subjects
Medicine, Science
Abstract

Myocilin is a broadly expressed protein that when mutated uniquely causes glaucoma. While no function has been ascribed to explain focal disease, some properties of myocilin are known. Myocilin is a cytoplasmic protein that also localizes to vesicles specifically as part of a large membrane-associated complex with properties similar to the SNARE machinery that function in vesicle fusion. Its role in vesicle dynamics has not been detailed, however myocilin intersects with the endocytic compartment at the level of the multivesicular body. Since internalized GPCRs are sorted in the multivesicular body, we investigated whether myocilin functions in ligand-dependent GPR143 endocytosis. Using recombinant systems we found that the kinetics of myocilin recruitment to biotinylated membrane proteins was similar to that of arrestin-3. We also co-localized myocilin with GPR143 and Arrestin-2 by confocal microscopy. However, wild-type myocilin differed significantly in its association kinetics and co-localization with internalized proteins from mutant myocilin (P370L or T377M). Moreover, we found that myocilin bound to the cytoplasmic tail of GPR143, an interaction mediated by its amino terminal helix-turn-helix domain. Hydrodynamic analyses show that the myocilin-GPR143 protein complex is >158 kD and stable in 500 mM KCl, but not 0.1% SDS. Collectively, data indicate that myocilin is recruited to the membrane compartment, interacting with GPCR proteins during ligand-mediated endocytosis and that GPCR signaling underlies pathology in myocilin glaucoma.

Published
2013
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134. Alpha-satellite RNA transcripts are repressed by centromere–nucleolus associations

Author

Karen H. Miga, Brittania Moodie, Jimmy Ly, Iain M. Cheeseman, Leah Bury, and Liliana S. McKay

Subjects
Transcription, Genetic, Nucleolus, QH301-705.5, Science, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, chemistry.chemical_compound, Transcription (biology), RNA polymerase, Gene expression, Centromere, Humans, nucleolus, Biology (General), Mitosis, mitosis, General Immunology and Microbiology, General Neuroscience, RNA, General Medicine, Cell Biology, Chromosomes and Gene Expression, Chromatin, Cell biology, kinetochore, alpha-satellite, chemistry, centromere, RNA, Satellite, Medicine, RNA, Long Noncoding, RNA Polymerase II, transcription, Cell Nucleolus, Research Article, Human
Abstract

Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA-smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere–nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.

Published
2020

136. Cell-Type-Specific Metabolic Profiling Achieved by Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Immunofluorescence Staining

Author

Xiaoai Zhao, Richard N. Zare, Zhenpeng Zhou, Xin Yan, Anne Brunet, and Andrew S. McKay

Subjects
In situ, Chemical imaging, Cell type, Spectrometry, Mass, Electrospray Ionization, Electrospray ionization, Fluorescent Antibody Technique, 010402 general chemistry, Mass spectrometry, 01 natural sciences, Mass spectrometry imaging, Article, Analytical Chemistry, Machine Learning, Mice, Prosencephalon, Animals, Neurons, Desorption electrospray ionization, Staining and Labeling, Chemistry, 010401 analytical chemistry, 0104 chemical sciences, Matrix-assisted laser desorption/ionization, Astrocytes, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Biophysics
Abstract

Cell-type-specific metabolic profiling in tissue with heterogeneous composition has been of great interest across all mass spectrometry imaging (MSI) technologies. We report here a powerful new chemical imaging capability in desorption electrospray ionization (DESI) MSI, which enables cell-type-specific and in situ metabolic profiling in complex tissue samples. We accomplish this by combining DESI-MSI with immunofluorescence staining using specific cell-type markers. We take advantage of the variable frequency of each distinct cell-type in the lateral septal nucleus (LSN) region of mouse forebrain. This allows computational deconvolution of the cell-type-specific metabolic profile in neurons and astrocytes by convex optimization - a machine learning method. Based on our approach, we observed 107 metabolites that show different distributions and intensities between astrocytes and neurons. We subsequently identified 23 metabolites using high resolution mass spectrometry (MS) and tandem MS, which include small metabolites such as adenosine and N-acetylaspartate previously associated with astrocytes and neurons, respectively, as well as accumulation of several phospholipid species in neurons which have not been studied before. Overall, this method overcomes the relatively low spatial resolution of DESI-MSI and provides a new platform for in situ metabolic investigation at the cell-type level in complex tissue samples with heterogeneous cell-type composition.

Published
2020

137. Change in Circulating Undercarboxylated Osteocalcin (ucOCN) Is Associated With Fat Accumulation in HIV-Seropositive Women

Author

Arnold Z. Olali, Qiuhu Shi, Kathleen M. Weber, Heather S. McKay, Phyllis C. Tien, Michael T. Yin, Anjali Sharma, Donald R. Hoover, Audrey L. French, Lena Al-Harthi, and Ryan D. Ross

Subjects
Cart, Adult, Osteocalcin, Physiology, HIV Infections, Article, Absorptiometry, Photon, Bone Density, Bayesian multivariate linear regression, Linear regression, HIV Seropositivity, Medicine, Humans, Pharmacology (medical), Bone mineral, biology, business.industry, virus diseases, Middle Aged, Viral Load, Trunk, CD4 Lymphocyte Count, Infectious Diseases, Adipose Tissue, biology.protein, Female, business, Viral load, Biomarkers, Hormone
Abstract

Background Bone mineral density (BMD) loss and fat accumulation are common in people living with HIV (PLWH). The bone-derived hormone, undercarboxylated osteocalcin (ucOCN) regulates fat metabolism. We investigated the relationship between ucOCN change and body fat change among perimenopausal/postmenopausal HIV-seronegative and HIV-seropositive women on long-term antiretrovirals. Methods Perimenopausal and postmenopausal women enrolled in the Women's Interagency HIV Study (WIHS) MSK sub-study underwent trunk and total fat assessment via dual x-ray absorptiometry (DXA) at study enrollment (index visit) and again two years later. Circulating ucOCN and carboxylated osteocalcin (cOCN) were also measured at the index and two-year visits. The correlation between the two-year change in ucOCN and cOCN and change in trunk and total fat was assessed as a function of HIV-serostatus using linear regression modeling. Multivariate linear regression assessed the association between ucOCN and cOCN change and total and trunk fat change after adjusting for sociodemographic variables. Linear regression models restricted to HIV-seropositive women were performed to examine the contributions of HIV specific factors (index CD4 count, viral load, and cART use) on the associations. Results Increased ucOCN over the two-year follow-up was associated with less trunk and total fat accumulation in models adjusting for HIV-serostatus and participants sociodemographics, while there was no association with cOCN and the fat parameters. None of the HIV-specific factors evaluated influenced the association between ucOCN and fat parameters. Conclusion The current study suggests that increases in ucOCN are associated with decreased fat accumulation in HIV-seronegative and HIV-seropositive postmenopausal women on long-term antiretroviral therapy.

Published
2020

138. Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience

Author

Sivesh K. Kamarajah, Pavlos Lykoudis, Richard Wilkin, D Nasralla, Iain S. Tait, Ricky H. Bhogal, Robert P. Sutcliffe, Nicola de Liguori Carino, Matthew J. Bowles, Ryan Baron, Asma Sultana, Krishna Menon, Ali Arshad, Nigel B. Jamieson, Alastair L. Young, Gourab Sen, James M. Halle-Smith, Bilal Al-Sarireh, Damien Durkin, Alex Navarro, Keith J. Roberts, C. Jones, Declan F.J. Dunne, Stephen J. Wigmore, S. McKay, Parthi Srinivasan, James Milburn, Giuseppe Garcea, Manijeh Ghods-Ghorbani, C. Briggs, Duncan Spalding, A Kanwar, Nehal Shah, Simon Harper, Samir Pathak, Jonathan Rees, Hemant M. Kocher, Somaiah Aroori, Mike Silva, D. A. Stell, Jawad Ahmad, Adam E Frampton, and Andreas Prachalias

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pancreatic cancer, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Pandemic, medicine, Humans, Intensive care medicine, Pandemics, Aged, Hepatology, business.industry, SARS-CoV-2, Gastroenterology, Cancer, COVID-19, medicine.disease, United Kingdom, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Original Article, business, Healthcare providers
Abstract

Introduction: \ud The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic.\ud \ud Methods: \ud A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved.\ud \ud Results: \ud Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic.\ud \ud Conclusion: \ud The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Published
2020

139. Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses

Author

Mohammad Murshid Alam, Robert Hincapie, Roger C. Diehl, Jiri Schimer, Laura L. Kiessling, Carlos A. Sanhueza, Craig S. McKay, M. G. Finn, Cassie M. Jarvis, and Ke Xu

Subjects
Cellular immunity, T cell, T-Lymphocytes, General Physics and Astronomy, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, Proinflammatory cytokine, Mice, Immune system, Antigen, Polysaccharides, medicine, Animals, General Materials Science, Antigens, Immunity, Cellular, biology, Chemistry, General Engineering, Lectin, Dendritic cell, Dendritic Cells, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Cell biology, DC-SIGN, medicine.anatomical_structure, biology.protein, 0210 nano-technology
Abstract

Dendritic cells (DCs) are highly effective antigen-presenting cells that shape immune responses. Vaccines that deliver antigen to the DCs can harness their power. DC surface lectins recognize glycans not typically present on host tissue to facilitate antigen uptake and presentation. Vaccines that target these surface lectins should offer improved antigen delivery, but their efficacy will depend on how lectin targeting influences the T cell subtypes that result. We examined how antigen structure influences uptake and signaling from the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, CD209). Virus-like nanoparticles (VLPs) were engineered from bacteriophage Qβ to present an array of mannoside ligands. The VLPs were taken up by DCs and efficiently trafficked to endosomes. The signaling that ensued depended on the ligand displayed on the VLP: only those particles densely functionalized with an aryl mannoside, Qβ-Man(540,) elicited DC maturation and induced the expression of the proinflammatory cytokines characteristic of a T helper type 1 (T(H)1)-like immune response. This effect was traced to differential binding to DC-SIGN at the acidic pH of the endosome. Mice were immunized with a VLP bearing the aryl mannoside and a peptide antigen (Qβ-Ova-Man(540)) had antigen-specific responses, including the production of CD4(+) T cells producing the activating cytokines interferon-γ and tumor necrosis factor-α. A T(H)1 response is critical for intracellular pathogens (e.g., viruses) and cancer; thus, our data highlight the value of targeting DC lectins for antigen delivery and validate the utility of DC-targeted VLPs as vaccine vehicles that induce cellular immunity.

Published
2020

140. The experience of deployed dental teams on Operation Herrick: dentists at war in Afghanistan

Author

Laura S McKay

Subjects
Afghan Campaign 2001, Lived experience, Dentists, MEDLINE, Afghanistan, 030206 dentistry, medicine.disease, 03 medical and health sciences, Military personnel, 0302 clinical medicine, Military Personnel, Political science, Military operation, medicine, Humans, 030212 general & internal medicine, Medical emergency, General Dentistry
Abstract

Operation Herrick was the British military operation in Afghanistan that occurred between 2002 and 2014; the most recent, large-scale and publicly conducted war in British history. During this time, over 60 British military dental teams deployed as part of the UK Medical Group, their primary role being the treatment of dental emergencies in UK Armed Forces. There are numerous publications citing statistics regarding the rates and nature of dental casualties on operations, their management and how this affects operational capability. This article instead aims to give a more generalised insight into the lived experience of an Army dentist deployed on Operation Herrick.

Published
2020

141. Controversies regarding shielding and susceptibility to COVID‐19 disease in liver transplant recipients in the United Kingdom

Author

David Mutimer, Ye Htun Oo, Darius F. Mirza, John Isaac, S. McKay, Hermien Hartog, Moira Perrin, Hanns Lembach, Angus Hann, and Thamara Perera

Subjects
Cross infection, 2019-20 coronavirus outbreak, Transplantation, Coronavirus disease 2019 (COVID-19), Middle East respiratory syndrome coronavirus, business.industry, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, Liver transplantation, medicine.disease_cause, Virology, Infectious Diseases, medicine, business
Published
2020
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143. Severe Sepsis Mimicking Primary Nonfunction Following Liver Transplantation: Normothermic Machine Perfusion Is a Potential Environment for Bacterial Overgrowth and Transmission From Donor to Recipient. A Case Report

Author

B. Dassanayake, David C. Bartlett, A. Carvalheiro, M. T. P. R. Perera, S. McKay, Hanns Lembach, Matthew J. Armstrong, Angus Hann, M. David, and Neil Rajoriya

Subjects
medicine.medical_specialty, medicine.medical_treatment, Organ Preservation Solutions, Liver transplantation, Gastroenterology, Sepsis, Immune system, Postoperative Complications, Internal medicine, medicine, Humans, Transplantation, Machine perfusion, business.industry, Acute-phase protein, Organ Preservation, Middle Aged, medicine.disease, Tissue Donors, Portal vein thrombosis, Liver Transplantation, Perfusion, medicine.anatomical_structure, Surgery, Female, business, Drug Contamination, Artery
Abstract

Primary nonfunction (PNF) in the early postoperative period following liver transplantation is fatal if not managed appropriately with early retransplantation. Severe early allograft dysfunction can mimic PNF. The identification of treatable causative factors such as sepsis, hepatic artery, or portal vein thrombosis is essential to distinguish it from PNF, and their early management may avoid the need for retransplantation. In this article, we describe a case of sepsis-induced severe liver dysfunction from a contaminated graft perfused with normothermic machine perfusion (NMP), which presented in a manner similar to PNF. The implications of graft contamination are poorly described. To our knowledge, this is the first report of bacterial contamination of a graft that underwent NMP and subsequently caused severe sepsis in the recipient. The conditions created with NMP may be optimal for certain micro-organisms to thrive. The role of the liver in the immune system is complex as it provides an essential barrier to enterically derived portal venous pathogens and produces numerous acute phase proteins that augment the systemic immune response. Additionally, the liver is also known to restrain harmful and excessive systemic immune responses such as those that occur with the sepsis syndrome. The relationship between bacterial graft contamination, sepsis, and graft dysfunction may be multidirectional.

Published
2020

144. Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations

Author

Brittania Moodie, Iain M. Cheeseman, Karen H. Miga, Leah Bury, and Liliana S. McKay

Subjects
0303 health sciences, Cell division, Nucleolus, 030302 biochemistry & molecular biology, RNA, Cell cycle, Biology, Chromatin, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Transcription (biology), RNA polymerase, Centromere, 030304 developmental biology
Abstract

Centromeres play a fundamental role in chromosome segregation. Although originally thought to be silent chromosomal regions, centromeres are actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA smFISH foci fluctuate in their levels over the cell cycle and do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Our results demonstrate that alpha-satellite expression occurs through RNA Polymerase II-dependent transcription, but does not require centromere proteins and other cell division components. Instead, our work implicates centromere-nucleolar associations as the major factor regulating alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels, explaining variations in alpha-satellite RNA between cell lines. In addition, alpha-satellite transcript levels increase substantially when the nucleolus is disrupted. Together, our results are inconsistent with a direct, physical role for alpha-satellite transcripts in cell division processes, and instead support a role for ongoing transcription in promoting centromere chromatin dynamics. The control of alpha-satellite transcription by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.

Published
2020

145. A G-Protein Coupled Receptor and Macular Degeneration

Author

Brian S. McKay and Anna G. Figueroa

Subjects
0301 basic medicine, Retinal degeneration, macular degeneration, genetic structures, G-protein, L-DOPA, Disease, Review, AMD, Bioinformatics, Receptors, G-Protein-Coupled, Melanin, 03 medical and health sciences, Basal (phylogenetics), chemistry.chemical_compound, 0302 clinical medicine, OA1, medicine, Humans, GPR143, Eye Proteins, lcsh:QH301-705.5, G protein-coupled receptor, Retinal pigment epithelium, Membrane Glycoproteins, business.industry, Retinal, General Medicine, Macular degeneration, medicine.disease, eye diseases, melanin, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), chemistry, 030221 ophthalmology & optometry, sense organs, RPE, business
Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.

Published
2020

147. Structure and Drug Binding of the SARS-CoV-2 Envelope Protein in Phospholipid Bilayers

Author

Mandala, Venkata S. McKay, Matthew J. Shcherbakov, Alexander A. Dregni, Aurelio J. Kolocouris, Antonios Hong, Mei

Subjects
viruses
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic. Successful development of vaccines and antivirals against SARS-CoV-2 requires a comprehensive understanding of the essential proteins of the virus. The envelope (E) protein of SARS-CoV-2 assembles into a cation-selective channel that mediates virus budding, release, and host inflammation response. E blockage reduces virus pathogenicity while E deletion attenuates the virus. Here we report the 2.4 Å structure and drug-binding site of E's transmembrane (TM) domain, determined using solid-state nuclear magnetic resonance (NMR) spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow central pore. The middle of the TM segment is distorted from the ideal a-helical geometry due to three regularly spaced phenylalanine residues, which stack within each helix and between neighboring helices. These aromatic interactions, together with interhelical Val and Leu interdigitation, cause a dehydrated pore compared to the viroporins of influenza and HIV viruses. Hexamethylene amiloride and amantadine bind shallowly to polar residues at the N-terminal lumen, while acidic pH affects the C-terminal conformation. These results indicate that SARS-CoV-2 E forms a structurally robust but bipartite channel whose N- and C-terminal halves can interact with drugs, ions and other viral and host proteins semi-independently. This structure establishes the atomic basis for designing E inhibitors as antiviral drugs against SARS-CoV-2.

Published
2020

148. Changes in brain activity following the voluntary control of empathy

Author

Lawrie S. McKay, Christian Keysers, Abdel R. Abdelgabar, Valeria Gazzola, K.C. Borja Jimenez, L. De Angelis, Netherlands Institute for Neuroscience (NIN), and Brein en Cognitie (Psychologie, FMG)

Subjects
Adult, Male, Brain activity and meditation, Cognitive Neuroscience, media_common.quotation_subject, Motion Pictures, Empathy, 050105 experimental psychology, lcsh:RC321-571, Intersubject correlation, 03 medical and health sciences, Functional connectivity, Young Adult, 0302 clinical medicine, Theory of mind, Humans, 0501 psychology and cognitive sciences, Control (linguistics), lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, media_common, Reappraisal, Emotion regulation, 05 social sciences, Perspective (graphical), Brain, Magnetic Resonance Imaging, Neurology, Turnover, Cognitive control, Psychology, 030217 neurology & neurosurgery, Photic Stimulation, Cognitive psychology
Abstract

In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto our own emotions has received comparatively less attention. Here, we therefore measured brain activity while participants watched emotional Hollywood movies under two different instructions: to rate the main characters' emotions by empathizing with them, or to do so while keeping a detached perspective. We found that participants yielded highly consistent and similar ratings of emotions under both conditions. Using intersubject correlation-based analyses we found that, when encouraged to empathize, participants' brain activity in limbic (including cingulate and putamen) and somatomotor regions (including premotor, SI and SII) synchronized more during the movie than when encouraged to detach. Using intersubject functional connectivity we found that comparing the empathic and detached perspectives revealed widespread increases in functional connectivity between large scale networks. Our findings contribute to the increasing awareness that we have voluntary control over the neural mechanisms through which we process the emotions of others.

Published
2020

149. Poetry

Author

David D. Preiss, Sarah F. Lynch, Alexander S. McKay, and James C. Kaufman

Published
2020

150. Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice

Author

Ulrika Westerlind, Christian Pett, Suttipun Sungsuwan, Anthony Allmon, Craig S. McKay, Xuanjun Wu, Xuefei Huang, Zhaojun Yin, Rupali Das, Jin Yu, Claire Baniel, Manuel Schorlemer, Sherif Ramadan, Trevor G. Gohl, and M. G. Finn

Subjects
Male, 0301 basic medicine, Transgene, Gastropoda, Breast Neoplasms, Mice, Transgenic, Computational biology, Cancer Vaccines, digestive system, Biochemistry, Antibodies, Article, Catalysis, Epitope, Epitopes, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Colloid and Surface Chemistry, Antigen, Animals, Humans, Amino Acid Sequence, Neoplasm Metastasis, skin and connective tissue diseases, neoplasms, Peptide sequence, MUC1, Allolevivirus, Chemistry, Extramural, Mucin-1, General Chemistry, Peptide Fragments, biological factors, digestive system diseases, Mice, Inbred C57BL, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Hemocyanins, Female
Abstract

Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUCl antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20–22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.

Published
2018

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