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Hanieh Yaghootkar, Michael P Bancks, Sam E Jones, Aaron McDaid, Robin Beaumont, Louise Donnelly, Andrew R Wood, Archie Campbell, Jessica Tyrrell, Lynne J Hocking, Marcus A Tuke, Katherine S Ruth, Ewan R Pearson, Anna Murray, Rachel M Freathy, Patricia B Munroe, Caroline Hayward, Colin Palmer, Michael N Weedon, James S Pankow, Timothy M Frayling, Zoltán Kutalik
As genetic association studies increase in size to 100,000s of individuals, subtle biases may influence conclusions. One possible bias is "index event bias" (IEB) that appears due to the stratification by, or enrichment for, disease status when testing associations between genetic variants and a disease-associated trait. We aimed to test the extent to which IEB influences some known trait associations in a range of study designs and provide a statistical framework for assessing future associations. Analysing data from 113,203 non-diabetic UK Biobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (BMI-decreasing) and one (near MTNR1B) underestimated (BMI-increasing) associations among 11 type 2 diabetes risk alleles (at P < 0...
December 30, 2016: Human Molecular Genetics
E Sam, C Carbonneil
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Julian Lange, Shintaro Yamada, Sam E Tischfield, Jing Pan, Seoyoung Kim, Xuan Zhu, Nicholas D Socci, Maria Jasin, Scott Keeney
Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9...
October 20, 2016: Cell
Sam E Mason, James M Kinross, Jane Hendricks, Thanjakumar H Arulampalam
BACKGROUND: Surgical Site Infection (SSI) occurs in 9 % of laparoscopic colorectal surgery. Warming and humidifying carbon dioxide (CO2) used for peritoneal insufflation may protect against SSI by avoiding postoperative hypothermia (itself a risk factor for SSI). This study aimed to assess the impact of CO2 conditioning on postoperative hypothermia and SSI and to perform a cost-effectiveness analysis. METHODS: A retrospective cohort study of patients undergoing elective laparoscopic colorectal resection was performed at a single UK specialist centre...
October 12, 2016: Surgical Endoscopy
Sam E Karelitz, Sven Uthicke, Shawna A Foo, Mike F Barker, Maria Byrne, Danilo Pecorino, Miles D Lamare
As the ocean warms, thermal tolerance of developmental stages may be a key driver of changes in the geographical distributions and abundance of marine invertebrates. Additional stressors such as ocean acidification may influence developmental thermal windows and are therefore important considerations for predicting distributions of species under climate change scenarios. The effects of reduced seawater pH on the thermal windows of fertilization, embryology and larval morphology were examined using five echinoderm species: two polar (Sterechinus neumayeri and Odontaster validus), two temperate (Fellaster zelandiae and Patiriella regularis) and one tropical (Arachnoides placenta)...
August 6, 2016: Global Change Biology
Arun V Ravindran, Lynda G Balneaves, Guy Faulkner, Abigail Ortiz, Diane McIntosh, Rachel L Morehouse, Lakshmi Ravindran, Lakshmi N Yatham, Sidney H Kennedy, Raymond W Lam, Glenda M MacQueen, Roumen V Milev, Sagar V Parikh
BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses...
September 2016: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Nicholas L Opie, Sam E John, Gil S Rind, Stephen M Ronayne, David B Grayden, Anthony N Burkitt, Clive N May, Terence J O'Brien, Thomas J Oxley
OBJECTIVE: Recently, we reported a minimally invasive stent-electrode array capable of recording neural signals from within a blood vessel. We now investigate the use of electrochemical impedance spectroscopy (EIS) measurements to infer changes occurring to the electrode-tissue interface from devices implanted in a cohort of sheep for up to 190 days. APPROACH: In a cohort of 15 sheep, endovascular stent-electrode arrays were implanted in the superior sagittal sinus overlying the motor cortex for up to 190 days...
August 2016: Journal of Neural Engineering
Nicholas L Opie, Nicole R van der Nagel, Sam E John, Kirstan Vessey, Gil S Rind, Stephen M Ronayne, Erica L Fletcher, Clive N May, Terence OBrien, Thomas Oxley
OBJECTIVE: Recently, we reported the development of a stent-mounted electrode array (Stentrode™) capable of chronically recording neural signals from within a blood vessel with high fidelity. Preliminary data suggested incorporation of the Stentrode™ into the blood vessel wall was associated with improved recording sensitivity. We now investigate neointimal incorporation of the Stentrode™, implanted in a cohort of sheep for up to 190 days. METHODS: Micro-CT, obtained from the Imaging and Medical Beamline at the Australian Synchrotron, and histomorphometic techniques developed specifically for evaluation of cerebral vasculature implanted with a stent-electrode array were compared as measures to assess device incorporation and vessel patency...
June 21, 2016: IEEE Transactions on Bio-medical Engineering
Lori S Katz, Sam E Park, Geta Cojucar, Cristi Huffman, Sarah Douglas
The Warrior Renew sexual trauma treatment program proposes to target perceived attachment style and the internal working models of interpersonal relationships. This study examined scores on the Relationships Scales Questionnaire and Brief Symptom Inventory pre- and posttreatment in a sample of 62 female veterans who graduated the program. Findings revealed that graduates of Warrior Renew reported significant decreases in fearful and dismissive insecure attachment and significant increases in secure attachment...
2016: Violence and Victims
Ehsan Rahimy, Michael W Gaynon, Yannis M Paulus, Janet L Alexander, Sam E Mansour
No abstract text is available yet for this article.
July 1, 2016: JAMA Ophthalmology
Mayuramas Sang-Ngern, Ui Joung Youn, Eun-Jung Park, Tamara P Kondratyuk, Charles J Simmons, Marisa M Wall, Michael Ruf, Sam E Lorch, Ethyn Leong, John M Pezzuto, Leng Chee Chang
Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7...
June 15, 2016: Bioorganic & Medicinal Chemistry Letters
Hanieh Yaghootkar, Luca A Lotta, Jessica Tyrrell, Roelof A J Smit, Sam E Jones, Louise Donnelly, Robin Beaumont, Archie Campbell, Marcus A Tuke, Caroline Hayward, Katherine S Ruth, Sandosh Padmanabhan, J Wouter Jukema, Colin C Palmer, Andrew Hattersley, Rachel M Freathy, Claudia Langenberg, Nicholas J Wareham, Andrew R Wood, Anna Murray, Michael N Weedon, Naveed Sattar, Ewan Pearson, Robert A Scott, Timothy M Frayling
Recent genetic studies have identified some alleles that are associated with higher BMI but lower risk of type 2 diabetes, hypertension, and heart disease. These "favorable adiposity" alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, to test for interactions between BMI and favorable adiposity genetics, and to test effects separately in men and women...
August 2016: Diabetes
Michel A Picardo, Josh Merel, Kalman A Katlowitz, Daniela Vallentin, Daniel E Okobi, Sam E Benezra, Rachel C Clary, Eftychios A Pnevmatikakis, Liam Paninski, Michael A Long
The zebra finch brain features a set of clearly defined and hierarchically arranged motor nuclei that are selectively responsible for producing singing behavior. One of these regions, a critical forebrain structure called HVC, contains premotor neurons that are active at precise time points during song production. However, the neural representation of this behavior at a population level remains elusive. We used two-photon microscopy to monitor ensemble activity during singing, integrating across multiple trials by adopting a Bayesian inference approach to more precisely estimate burst timing...
May 18, 2016: Neuron
Roberta K Sefcik, Nicholas L Opie, Sam E John, Christopher P Kellner, J Mocco, Thomas J Oxley
Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings...
May 2016: Neurosurgical Focus
Alberto Mangano, Georgios D Lianos, Dimitrios H Roukos, Sam E Mason, Hoon Yub Kim, Gianlorenzo Dionigi
Neuroendocrine tumors (NETs) are rare and heterogeneous tumors and there is a paucity of randomized clinical trials evaluating the different therapeutic strategies. Over recent years, some important molecular aspects have been investigated and multiple targeted therapies are currently available. One of the most promising targets for the therapy of NETs are the mTOR and angiogenic growth factor receptors. The advent of the inhibitors of the mTOR pathway, tyrosine kinase inhibitors and of somatostatin analogs have shown their efficacy in randomized clinical trials in terms of implementing clinical hormone-induced syndromes and progression-free survival of advanced NETs...
2016: Future Oncology
Thomas J Oxley, Nicholas L Opie, Sam E John, Gil S Rind, Stephen M Ronayne, Tracey L Wheeler, Jack W Judy, Alan J McDonald, Anthony Dornom, Timothy J H Lovell, Christopher Steward, David J Garrett, Bradford A Moffat, Elaine H Lui, Nawaf Yassi, Bruce C V Campbell, Yan T Wong, Kate E Fox, Ewan S Nurse, Iwan E Bennett, Sébastien H Bauquier, Kishan A Liyanage, Nicole R van der Nagel, Piero Perucca, Arman Ahnood, Katherine P Gill, Bernard Yan, Leonid Churilov, Christopher R French, Patricia M Desmond, Malcolm K Horne, Lynette Kiers, Steven Prawer, Stephen M Davis, Anthony N Burkitt, Peter J Mitchell, David B Grayden, Clive N May, Terence J O'Brien
High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode)...
March 2016: Nature Biotechnology
Marian C Bryan, Daniel J Burdick, Bryan K Chan, Yuan Chen, Saundra Clausen, Jennafer Dotson, Charles Eigenbrot, Richard Elliott, Emily J Hanan, Robert Heald, Philip Jackson, Hank La, Michael Lainchbury, Shiva Malek, Sam E Mann, Hans E Purkey, Gabriele Schaefer, Stephen Schmidt, Eileen Seward, Steve Sideris, Shumei Wang, Ivana Yen, Christine Yu, Timothy P Heffron
The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein.
January 14, 2016: ACS Medicinal Chemistry Letters
Shin-Yi Chiou, Sam E A Gottardi, Paul W Hodges, Paul H Strutton
Evidence suggests that the primary motor cortex (M1) is involved in both voluntary, goal-directed movements and in postural control. Trunk muscles are involved in both tasks, however, the extent to which M1 controls these muscles in trunk flexion/extension (voluntary movement) and in rapid shoulder flexion (postural control) remains unclear. The purpose of this study was to investigate this question by examining excitability of corticospinal inputs to trunk muscles during voluntary and postural tasks. Twenty healthy adults participated...
2016: PloS One
Jonathan I Benichov, Sam E Benezra, Daniela Vallentin, Eitan Globerson, Michael A Long, Ofer Tchernichovski
The dichotomy between vocal learners and non-learners is a fundamental distinction in the study of animal communication. Male zebra finches (Taeniopygia guttata) are vocal learners that acquire a song resembling their tutors', whereas females can only produce innate calls. The acoustic structure of short calls, produced by both males and females, is not learned. However, these calls can be precisely coordinated across individuals. To examine how birds learn to synchronize their calls, we developed a vocal robot that exchanges calls with a partner bird...
February 8, 2016: Current Biology: CB
Lara Pizzorno
The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents...
August 2015: Integrative Medicine
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