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David Holmes

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https://www.readbyqxmd.com/read/28067910/exploring-the-genetic-architecture-of-inflammatory-bowel-disease-by-whole-genome-sequencing-identifies-association-at-adcy7
#1
Yang Luo, Katrina M de Lange, Luke Jostins, Loukas Moutsianas, Joshua Randall, Nicholas A Kennedy, Christopher A Lamb, Shane McCarthy, Tariq Ahmad, Cathryn Edwards, Eva Goncalves Serra, Ailsa Hart, Chris Hawkey, John C Mansfield, Craig Mowat, William G Newman, Sam Nichols, Martin Pollard, Jack Satsangi, Alison Simmons, Mark Tremelling, Holm Uhlig, David C Wilson, James C Lee, Natalie J Prescott, Charlie W Lees, Christopher G Mathew, Miles Parkes, Jeffrey C Barrett, Carl A Anderson
To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28067908/genome-wide-association-study-implicates-immune-activation-of-multiple-integrin-genes-in-inflammatory-bowel-disease
#2
Katrina M de Lange, Loukas Moutsianas, James C Lee, Christopher A Lamb, Yang Luo, Nicholas A Kennedy, Luke Jostins, Daniel L Rice, Javier Gutierrez-Achury, Sun-Gou Ji, Graham Heap, Elaine R Nimmo, Cathryn Edwards, Paul Henderson, Craig Mowat, Jeremy Sanderson, Jack Satsangi, Alison Simmons, David C Wilson, Mark Tremelling, Ailsa Hart, Christopher G Mathew, William G Newman, Miles Parkes, Charlie W Lees, Holm Uhlig, Chris Hawkey, Natalie J Prescott, Tariq Ahmad, John C Mansfield, Carl A Anderson, Jeffrey C Barrett
Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28041968/medicines-for-pediatric-patients-biopharmaceutical-developmental-and-regulatory-considerations
#3
David P Elder, René Holm, Martin Kuentz
This commentary reflects current developments in pediatric medicine. The underpinning legislation in both Europe and the US has led to the initiation of an increased number of clinical trials in the pediatric population, but there are still a number of outstanding issues within this field. These include the differences in the physiology between adults and the very heterogeneous nature of pediatric patients. There is an ongoing scientific debate on the applicability of a Pediatric Biopharmaceutical Classification System (PBCS) to define when waivers for bioequivalence studies can be supported by in vitro dissolution...
December 29, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28034624/determinants-of-denervation-independent-depletion-of-putamen-dopamine-in-parkinson-s-disease-and-multiple-system-atrophy
#4
David S Goldstein, Patti Sullivan, Courtney Holmes, Deborah C Mash, Irwin J Kopin, Yehonatan Sharabi
BACKGROUND: Severe putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA...
December 15, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28007201/incidence-characteristics-predictors-and%C3%A2-outcomes-of-repeat-revascularization-after-percutaneous-coronary-intervention-and-coronary-artery-bypass-grafting-the-syntax-trial-at-5-years
#5
Catalina A Parasca, Stuart J Head, Milan Milojevic, Michael J Mack, Patrick W Serruys, Marie-Claude Morice, Friedrich W Mohr, Ted E Feldman, Antonio Colombo, Keith D Dawkins, David R Holmes, Pieter A Kappetein
OBJECTIVES: The study sought to determine the incidence, predictors, characteristics, and outcomes of repeat revascularization during 5-year follow-up of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) trial. BACKGROUND: Limited in-depth long-term data on repeat revascularization are available from randomized trials comparing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: Incidence and timing of repeat revascularization and its relation to the long-term composite safety endpoint of death, stroke, and myocardial infarction were analyzed in the SYNTAX trial (n = 1,800) using Kaplan-Meier analysis...
December 26, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28007198/transseptal-techniques-for-emerging%C3%A2-structural-heart-interventions
#6
REVIEW
Mohamad Alkhouli, Charanjit S Rihal, David R Holmes
The development of new transseptal transcatheter interventions for patients with structural heart disease is fueling increasing interest in transseptal puncture techniques. The authors review contemporary transseptal puncture indications and techniques and provide a step-by-step approach to challenging transseptal access and procedural complications.
December 26, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28001014/stroke-prevention-in-atrial-fibrillation-with-left-atrial-appendage-closure
#7
Chad J Zack, Erin A Fender, David R Holmes
Patients with atrial fibrillation (AF) are at risk for stroke and thromboembolism. Oral anticoagulants (OAC) are effective therapies to reduce the risk of stroke; however these agents also increase the risk of bleeding complications. Concerns over bleeding contribute to significant under treatment and leave a substantial proportion of patients at risk for a serious or life-threatening stroke. Identification of the left atrial appendage (LAA) as the major site of pathogenic thrombus formation in AF patients has led to the development of devices which exclude the appendage from systemic circulation...
December 20, 2016: Minerva Medica
https://www.readbyqxmd.com/read/27993938/direct-to-consumer-testing
#8
Michelle Li, Eleftherios P Diamandis, David Grenache, Michael J Joyner, Daniel T Holmes, Rodger Seccombe
No abstract text is available yet for this article.
December 19, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27990496/lupus-like-immune-complex-mediated-glomerulonephritis-in-patients-with-hepatitis-c-virus-infection-treated-with-oral-interferon-free-direct-acting-antiviral-therapy
#9
Meghan E Sise, Jessica Wisocky, Ivy A Rosales, Donald Chute, Jacinta A Holmes, Kristin M Corapi, Jodie L Babitt, Jessica S Tangren, Nikroo Hashemi, Andrew L Lundquist, Winfred W Williams, David B Mount, Karin L Andersson, Helmut G Rennke, R Neal Smith, Robert Colvin, Ravi I Thadhani, Raymond T Chung
Novel, all-oral interferon-free direct-acting antiviral agents have revolutionized the management of hepatitis C virus (HCV) infection by producing exceptional cure rates with minimal adverse events. While provocation or exacerbation of autoimmunity has been reported in HCV-infected patients receiving interferon, this phenomenon has not been reported in patients receiving interferon-free HCV therapy. We report the occurrence of three cases of lupus-like immune complex-mediated glomerulonephritis occurring shortly after exposure to sofosbuvir-based direct-acting antiviral therapies...
September 2016: KI Reports
https://www.readbyqxmd.com/read/27988322/a-multi-centre-evaluation-of-eleven-clinically-feasible-brain-pet-mri-attenuation-correction-techniques-using-a-large-cohort-of-patients
#10
Claes N Ladefoged, Ian Law, Udunna Anazodo, Keith St Lawrence, David Izquierdo-Garcia, Ciprian Catana, Ninon Burgos, M Jorge Cardoso, Sebastien Ourselin, Brian Hutton, Inés Mérida, Nicolas Costes, Alexander Hammers, Didier Benoit, Søren Holm, Meher Juttukonda, Hongyu An, Jorge Cabello, Mathias Lukas, Stephan Nekolla, Sibylle Ziegler, Matthias Fenchel, Bjoern Jakoby, Michael E Casey, Tammie Benzinger, Liselotte Højgaard, Adam E Hansen, Flemming L Andersen
AIM: To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based...
December 14, 2016: NeuroImage
https://www.readbyqxmd.com/read/27984354/predictors-of-suboptimal-follow-up-in-pediatric-cancer-survivors
#11
Leana May, David D Schwartz, Ernest Frugé, Larry Laufman, Suzanne Holm, Kala Kamdar, Lynnette Harris, Julienne Brackett, Sule Unal, Gulsah Tanyildiz, Rosalind Bryant, Hilary Suzawa, Zoann Dreyer, M Fatih Okcu
Attendance to follow-up care after completion of cancer treatment is an understudied area. We examined demographic, clinical, and socioeconomic predictors of follow-up by pediatric cancer patients at a large center in 442 newly diagnosed patients using multivariable logistic regression analyses. Patients who did not return to clinic for at least 1000 days were considered lost to follow-up. Two hundred forty-two (54.8%) patients were lost. In multivariable analyses, the following variables were independent predictors of being lost to follow-up: treatment with surgery alone (odds ratio [OR]=6...
December 14, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27983735/dyslipidaemia-predicting-the-benefits-and-risks-of-pcsk9-inhibition
#12
David Holmes
No abstract text is available yet for this article.
December 16, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27979210/mashing-with-unmalted-sorghum-using-a-novel-low-temperature-enzyme-system-impacts-of-sorghum-grain-composition-and-microstructure
#13
Calum P Holmes, John Casey, David J Cook
Brewing lager beers from unmalted sorghum traditionally requires the use of high temperature mashing and exogenous enzymes to ensure adequate starch conversion. Here, a novel low-temperature mashing system is compared to a more traditional mash in terms of the wort quality produced (laboratory scale) from five unmalted sorghums (2 brewing and 3 non-brewing varieties). The low temperature mash generated worts of comparable quality to those resulting from a traditional energy intensive mash protocol. Furthermore, its performance was less dependant on sorghum raw material quality, such that it may facilitate the use of what were previously considered non-brewing varieties...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27969992/tct-615-do-patients-with-ckd-benefit-from-left-atrial-appendage-closure-laac-with-watchman-insights-from-protect-af
#14
Miguel Valderrabano, Matthew Price, Vivek Reddy, Maurice Buchbinder, David Holmes, Horst Sievert, Zoltan Turi, Nicole Gordon, Chris Mullin, Peter Sick, Patricia Best
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27969991/tct-617-cost-effectiveness-following-treatment-initiation-of-stroke-reduction-strategies-in-non-valvular-atrial-fibrillation-warfarin-vs-noacs-vs-left-atrial-appendage-closure
#15
Vivek Reddy, Ronald Akehurst, Meghan Gavaghan, Stacey Amorosi, David Holmes
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27969662/tct-314-the-impact-of-chronic-kidney-disease-on-outcomes-following-percutaneous-coronary-interventions-versus-coronary-artery-bypass-grafting-in-patients-with-complex-coronary-artery-disease-5-year-follow-up-of-the-syntax-trial
#16
Milan Milojevic, Stuart Head, Michael Mack, Friedrich Mohr, Marie-Claude Morice, Keith Dawkins, David Holmes, Patrick Serruys, A Pieter Kappetein
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27969610/tct-26-long-term-event-rates-for-left-atrial-appendage-closure-with-watchman-protect-af-5-year-and-prevail-3-year-follow-up
#17
Vivek Reddy, Matthew Price, Miguel Valderrabano, Jose Sanchez, Shephal Doshi, Nicole Gordon, David Holmes
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27956264/2016-annual-report-of-the-society-of-thoracic-surgeons-american-college-of-cardiology-transcatheter-valve-therapy-registry
#18
Frederick L Grover, Sreekanth Vemulapalli, John D Carroll, Fred H Edwards, Michael J Mack, Vinod H Thourani, Ralph G Brindis, David M Shahian, Carlos E Ruiz, Jeffrey P Jacobs, George Hanzel, Joseph E Bavaria, E Murat Tuzcu, Eric D Peterson, Susan Fitzgerald, Matina Kourtis, Joan Michaels, Barbara Christensen, William F Seward, Kathleen Hewitt, David R Holmes
BACKGROUND: The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) OBJECTIVES: This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. METHODS: Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry...
December 2, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27955994/2016-annual-report-of-the-society-of-thoracic-surgeons-american-college-of-cardiology-transcatheter-valve-therapy-registry
#19
Frederick L Grover, Sreekanth Vemulapalli, John D Carroll, Fred H Edwards, Michael J Mack, Vinod H Thourani, Ralph G Brindis, David M Shahian, Carlos E Ruiz, Jeffrey P Jacobs, George Hanzel, Joseph E Bavaria, E Murat Tuzcu, Eric D Peterson, Susan Fitzgerald, Matina Kourtis, Joan Michaels, Barbara Christensen, William F Seward, Kathleen Hewitt, David R Holmes
BACKGROUND: The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) OBJECTIVES: This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. METHODS: Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry...
December 3, 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27940542/arsenic-detoxification-by-geobacter-species
#20
Yan Dang, David J F Walker, Kaitlin E Vautour, Steven Dixon, Dawn E Holmes
: Insight into the mechanisms for arsenic detoxification by Geobacter species is expected to improve the understanding of global cycling of arsenic in iron rich subsurface sedimentary environments. Analysis of fourteen different Geobacter genomes showed that all of these species have genes coding for an arsenic detoxification system (ars operon), and several have genes required for arsenic respiration (arr operon) and methylation (arsM). Four arsenic repressor-like proteins were detected in the genome of G sulfurreducens, however, only one (ArsR1) regulated transcription of the ars operon...
December 9, 2016: Applied and Environmental Microbiology
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