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https://www.readbyqxmd.com/read/28230650/acr-appropriateness-criteria%C3%A2-resectable-pancreatic-cancer
#1
William E Jones, W Waren Suh, May Abdel-Wahab, Ross A Abrams, Nilofer Azad, Prajnan Das, Jadranka Dragovic, Karyn A Goodman, Salma K Jabbour, Andre A Konski, Albert C Koong, Rachit Kumar, Percy Lee, Timothy M Pawlik, William Small, Joseph M Herman
Management of resectable pancreatic adenocarcinoma continues to present a challenge due to a paucity of high-quality randomized studies. Administration of adjuvant chemotherapy is widely accepted due to the high risk of systemic spread associated with pancreatic adenocarcinoma, but the role of radiation therapy is less clear. This paper reviews literature associated with resectable pancreatic cancer to include prognostic factors to aid in the selection of patients appropriate for adjuvant therapies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel...
February 22, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28225674/inhibiting-plasma-kallikrein-for-hereditary-angioedema-prophylaxis
#2
Aleena Banerji, Paula Busse, Mustafa Shennak, William Lumry, Mark Davis-Lorton, Henry J Wedner, Joshua Jacobs, James Baker, Jonathan A Bernstein, Richard Lockey, H Henry Li, Timothy Craig, Marco Cicardi, Marc Riedl, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel J Sexton, Christopher TenHoor, Jon A Kenniston, Ryan Faucette, J Gordon Still, Harvey Kushner, Robert Mensah, Chris Stevens, Joseph C Biedenkapp, Yung Chyung, Burt Adelman
Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial...
23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28223796/stromelysin-2-mmp-10-facilitates-clearance-and-moderates-inflammation-and-cell-death-following-lung-exposure-to-long-multiwalled-carbon-nanotubes
#3
Tyler C Vandivort, Timothy P Birkland, Talita P Domiciano, Somenath Mitra, Terrance J Kavanagh, William C Parks
Multiwalled carbon nanotubes (MWCNTs) are nanomaterials composed of multiple layers of graphene cylinders with unique properties that make them valuable for a number of industries. However, rising global production has led to concerns regarding potential occupational exposures to them as raw materials during handling. This is especially true for long MWCNT fibers, whose aspect ratio has been posited to initiate pathology similar to that of asbestos. Matrix metalloproteinases (MMPs) are a class of extracellular endopeptidases that control various processes related to tissue repair, inflammation, and more...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28221285/genome-wide-methylation-analysis-of-a-large-population-sample-shows-neurological-pathways-involvement-in-chronic-widespread-musculoskeletal-pain-cwp
#4
Gregory Livshits, Ida Malkin, Maxim B Freidin, Yudong Xia, Fei Gao, Jun Wang, Timothy D Spector, Alex MacGregor, Jordana T Bell, Frances Mk Williams
Chronic widespread musculoskeletal pain (CWP), has a considerable heritable component, which remains to be explained. Epigenetic factors may contribute to and account for some of the heritability estimate. We analysed epigenome-wide methylation using MeDIPseq in whole blood DNA from 1708 monozygotic (MZ) and dizygotic (DZ) Caucasian twins having CWP prevalence of 19.9%. Longitudinally stable methylation bins (lsBINs), were established by testing repeated measurements conducted ≥3 years apart, n=292. DNA methylation variation at lsBINs was tested for association with CWP in a discovery set of 50 MZ twin pairs discordant for CWP, and in an independent dataset (n=1608 twins), and the results from the two samples were combined using Fisher's method...
February 15, 2017: Pain
https://www.readbyqxmd.com/read/28217912/cold-adaptation-of-the-antarctic-haloarchaea-halohasta-litchfieldiae-and-halorubrum-lacusprofundi
#5
Timothy J Williams, Yan Liao, Jun Ye, Rhiannon P Kuchel, Anne Poljak, Mark J Raftery, Ricardo Cavicchioli
Halohasta litchfieldiae represents ∼ 44% and Halorubrum lacusprofundi ∼ 10% of the hypersaline, perennially cold (≥ -20°C) Deep Lake community in Antarctica. We used proteomics and microscopy to define physiological responses of these haloarchaea to growth at high (30°C) and low (10 and 4°C) temperatures. The proteomic data indicate that both species responded to low temperature by modifying their cell envelope including protein N-glycosylation, maintaining osmotic balance and translation initiation, and modifying RNA turnover and tRNA modification...
February 20, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28213792/validation-of-the-american-joint-commission-on-cancer-ajcc-8th-edition-staging-system-for-patients-with-pancreatic-adenocarcinoma-a-surveillance-epidemiology-and-end-results-seer-analysis
#6
Sivesh K Kamarajah, William R Burns, Timothy L Frankel, Clifford S Cho, Hari Nathan
BACKGROUND: The 8th edition of the AJCC staging system for pancreatic cancer incorporated several significant changes. This study sought to evaluate this staging system and assess its strengths and weaknesses relative to the 7th edition AJCC staging system. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database (2004-2013), 8960 patients undergoing surgical resection for non-metastatic pancreatic adenocarcinoma were identified. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests...
February 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28211936/reduction-of-cyclophosphamide-dose-for-patients-with-subset-2-low-risk-rhabdomyosarcoma-is-associated-with-an-increased-risk-of-recurrence-a-report-from-the-soft-tissue-sarcoma-committee-of-the-children-s-oncology-group
#7
David O Walterhouse, Alberto S Pappo, Jane L Meza, John C Breneman, Andrea Hayes-Jordan, David M Parham, Timothy P Cripe, James R Anderson, William H Meyer, Douglas S Hawkins
BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m(2) ) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28211093/gsskat-rapid-gene-set-analysis-and-multiple-testing-correction-for-rare-variant-association-studies-using-weighted-linear-kernels
#8
Nicholas B Larson, Shannon McDonnell, Lisa Cannon Albright, Craig Teerlink, Janet Stanford, Elaine A Ostrander, William B Isaacs, Jianfeng Xu, Kathleen A Cooney, Ethan Lange, Johanna Schleutker, John D Carpten, Isaac Powell, Joan E Bailey-Wilson, Olivier Cussenot, Geraldine Cancel-Tassin, Graham G Giles, Robert J MacInnis, Christiane Maier, Alice S Whittemore, Chih-Lin Hsieh, Fredrik Wiklund, William J Catolona, William Foulkes, Diptasri Mandal, Rosalind Eeles, Zsofia Kote-Jarai, Michael J Ackerman, Timothy M Olson, Christopher J Klein, Stephen N Thibodeau, Daniel J Schaid
Next-generation sequencing technologies have afforded unprecedented characterization of low-frequency and rare genetic variation. Due to low power for single-variant testing, aggregative methods are commonly used to combine observed rare variation within a single gene. Causal variation may also aggregate across multiple genes within relevant biomolecular pathways. Kernel-machine regression and adaptive testing methods for aggregative rare-variant association testing have been demonstrated to be powerful approaches for pathway-level analysis, although these methods tend to be computationally intensive at high-variant dimensionality and require access to complete data...
February 16, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28209913/rapid-imaging-of-tumor-cell-death-in-vivo-using-the-c2a-domain-of-synaptotagmin-i
#9
André A Neves, Bangwen Xie, Sarah Fawcett, Israt S Alam, Timothy H Witney, Maaike M de Backer, Julia Summers, William Hughes, Sarah McGuire, Dmitry Soloviev, Jodie Miller, William J Howat, De-En Hu, Tiago B Rodrigues, David Y Lewis, Kevin M Brindle
Cell death is an important target for imaging the early response of tumors to treatment. We describe here validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of Synaptotagmin-I. Methods: The capability of near infrared fluorophore-labeled and 99mTechnetium- and (111)Indium-labeled derivatives of C2Am for imaging tumor cell death, using planar near infrared fluorescence (NIRF) imaging and single photon computed tomography (SPECT) respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209728/evaluation-of-cell-therapy-on-exercise-performance-and-limb-perfusion-in-peripheral-artery-disease-the-cctrn-patients-with-intermittent-claudication-injected-with-aldh-bright-cells-pace-trial
#10
Emerson C Perin, Michael P Murphy, Keith L March, Roberto Bolli, John Loughran, Phillip C Yang, Nicholas J Leeper, Ronald L Dalman, Jason Q Alexander, Timothy D Henry, Jay H Traverse, Carl J Pepine, R David Anderson, Scott Berceli, James T Willerson, Raja Muthupillai, Amir A Gahremanpour, Ganesh Raveendran, Omaida C Velazquez, Joshua M Hare, Ivonne H Schulman, Vijaykumar S Kasi, William R Hiatt, Bharath Ambale-Venkatesh, João A Lima, Doris A Taylor, Micheline M Resende, Adrian P Gee, April G Durett, Jeannette Bloom, Sara Richman, Patricia G'Sell, Shari Williams, Fouzia Khan, Elsie G Ross, Michelle R Santoso, JoAnne Goldman, Dana Leach, Eileen Handberg, Benjamin Y C Cheong, Nichole A Piece, Darcy DiFede, Barb Bruhn-Ding, Emily Caldwell, Judy Bettencourt, Dejian Lai, Linda B Piller, Lara M Simpson, Michelle Cohen, Shelly L Sayre, Rachel W Vojvodic, Lem Moyé, Ray F Ebert, Robert D Simari, Alan T Hirsch
Background -Atherosclerotic peripheral artery disease (PAD) affects 8-12% of Americans over 65 and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE is an NHLBI-sponsored, randomized, double-blind, placebo-controlled phase 2, exploratory clinical trial designed to assess safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in PAD patients and to explore associated claudication physiologic mechanisms...
February 16, 2017: Circulation
https://www.readbyqxmd.com/read/28202364/fatty-acid-synthase-modern-tumor-cell-biology-insights-into-a-classical-oncology-target
#11
REVIEW
Douglas Buckley, Gregory Duke, Timothy S Heuer, Marie O'Farrell, Allan Wagman, William McCulloch, George Kemble
Decades of preclinical and natural history studies have highlighted the potential of fatty acid synthase (FASN) as a bona fide drug target for oncology. This review will highlight the foundational concepts upon which this perspective is built. Published studies have shown high levels of FASN in patient tumor tissues are present at later stages of disease and this overexpression predicts poor prognosis. Preclinical studies have shown that experimental overexpression of FASN in previously normal cells leads to changes that are critical for establishing a tumor phenotype...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28199699/detection-of-the-florfenicol-resistance-gene-flor-in-chryseobacterium-isolates-from-rainbow-trout-exception-to-the-general-rule
#12
David W Verner-Jeffreys, Thomas Brazier, Ramon Y Perez, David Ryder, Roderick M Card, Timothy J Welch, Rowena Hoare, Thao Ngo, Nikki McLaren, Richard Ellis, Kerry L Bartie, Stephen W Feist, William M P Rowe, Alexandra Adams, Kim D Thompson
No abstract text is available yet for this article.
February 11, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28199403/comparison-of-microbiological-diagnosis-of-urinary-tract-infection-in-young-children-by-routine-health-service-laboratories-and-a-research-laboratory-diagnostic-cohort-study
#13
Kate Birnie, Alastair D Hay, Mandy Wootton, Robin Howe, Alasdair MacGowan, Penny Whiting, Michael Lawton, Brendan Delaney, Harriet Downing, Jan Dudley, William Hollingworth, Catherine Lisles, Paul Little, Kathryn O'Brien, Timothy Pickles, Kate Rumsby, Emma Thomas-Jones, Judith Van der Voort, Cherry-Ann Waldron, Kim Harman, Kerenza Hood, Christopher C Butler, Jonathan A C Sterne
OBJECTIVES: To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory. POPULATION AND METHODS: We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples...
2017: PloS One
https://www.readbyqxmd.com/read/28199314/whole-genome-landscape-of-pancreatic-neuroendocrine-tumours
#14
Aldo Scarpa, David K Chang, Katia Nones, Vincenzo Corbo, Ann-Marie Patch, Peter Bailey, Rita T Lawlor, Amber L Johns, David K Miller, Andrea Mafficini, Borislav Rusev, Maria Scardoni, Davide Antonello, Stefano Barbi, Katarzyna O Sikora, Sara Cingarlini, Caterina Vicentini, Skye McKay, Michael C J Quinn, Timothy J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne McLean, Craig Nourse, Ehsan Nourbakhsh, Peter J Wilson, Matthew J Anderson, J Lynn Fink, Felicity Newell, Nick Waddell, Oliver Holmes, Stephen H Kazakoff, Conrad Leonard, Scott Wood, Qinying Xu, Shivashankar Hiriyur Nagaraj, Eliana Amato, Irene Dalai, Samantha Bersani, Ivana Cataldo, Angelo P Dei Tos, Paola Capelli, Maria Vittoria Davì, Luca Landoni, Anna Malpaga, Marco Miotto, Vicki L J Whitehall, Barbara A Leggett, Janelle L Harris, Jonathan Harris, Marc D Jones, Jeremy Humphris, Lorraine A Chantrill, Venessa Chin, Adnan M Nagrial, Marina Pajic, Christopher J Scarlett, Andreia Pinho, Ilse Rooman, Christopher Toon, Jianmin Wu, Mark Pinese, Mark Cowley, Andrew Barbour, Amanda Mawson, Emily S Humphrey, Emily K Colvin, Angela Chou, Jessica A Lovell, Nigel B Jamieson, Fraser Duthie, Marie-Claude Gingras, William E Fisher, Rebecca A Dagg, Loretta M S Lau, Michael Lee, Hilda A Pickett, Roger R Reddel, Jaswinder S Samra, James G Kench, Neil D Merrett, Krishna Epari, Nam Q Nguyen, Nikolajs Zeps, Massimo Falconi, Michele Simbolo, Giovanni Butturini, George Van Buren, Stefano Partelli, Matteo Fassan, Kum Kum Khanna, Anthony J Gill, David A Wheeler, Richard A Gibbs, Elizabeth A Musgrove, Claudio Bassi, Giampaolo Tortora, Paolo Pederzoli, John V Pearson, Nicola Waddell, Andrew V Biankin, Sean M Grimmond
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28198722/triad-viii-nationwide-multicenter-evaluation-to-determine-whether-patient-video-testimonials-can-safely-help-ensure-appropriate-critical-versus-end-of-life-care
#15
Ferdinando L Mirarchi, Timothy E Cooney, Arvind Venkat, David Wang, Thaddeus M Pope, Abra L Fant, Stanley A Terman, Kevin M Klauer, Monica Williams-Murphy, Michael A Gisondi, Brian Clemency, Ankur A Doshi, Mari Siegel, Mary S Kraemer, Kate Aberger, Stephanie Harman, Neera Ahuja, Jestin N Carlson, Melody L Milliron, Kristopher K Hart, Chelsey D Gilbertson, Jason W Wilson, Larissa Mueller, Lori Brown, Bradley D Gordon
OBJECTIVE: End-of-life interventions should be predicated on consensus understanding of patient wishes. Written documents are not always understood; adding a video testimonial/message (VM) might improve clarity. Goals of this study were to (1) determine baseline rates of consensus in assigning code status and resuscitation decisions in critically ill scenarios and (2) determine whether adding a VM increases consensus. METHODS: We randomly assigned 2 web-based survey links to 1366 faculty and resident physicians at institutions with graduate medical education programs in emergency medicine, family practice, and internal medicine...
February 14, 2017: Journal of Patient Safety
https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#16
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196430/first-in-human-trial-of-a-type-i-positive-allosteric-modulator-of-alpha7-nicotinic-acetylcholine-receptors-pharmacokinetics-safety-and-evidence-for-neurocognitive-effect-of-avl-3288
#17
Kelvin W Gee, Ann Olincy, Richard Kanner, Lynn Johnson, Derk Hogenkamp, Josette Harris, Minhtam Tran, Stephen A Edmonds, William Sauer, Ryan Yoshimura, Timothy Johnstone, Robert Freedman
Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor's characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects...
February 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28190605/the-importance-of-age-and-weight-on-cavopulmonary-shunt-stage-ii-outcomes-after-the-norwood-procedure-planned-versus-unplanned-surgery
#18
David J Barron, Intisar Ul Haq, Adrian Crucean, John Stickley, Phil Botha, Natasha Khan, Timothy J Jones, William J Brawn
OBJECTIVE: The study objective was to evaluate the outcomes of the cavopulmonary shunt after the Norwood procedure with a particular focus on age, weight, and whether surgery was planned or expedited by clinical findings. METHODS: We studied 297 consecutive patients with hypoplastic left heart syndrome undergoing the cavopulmonary shunt operation between 2002 and 2014. All patients underwent the Norwood procedure with a right ventricle to pulmonary artery conduit...
January 17, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28186266/mentoring-new-surgeons-can-we-avoid-the-learning-curve-%C3%A2
#19
Shafi Mussa, Nigel E Drury, John Stickley, Natasha E Khan, Timothy J Jones, David J Barron, William J Brawn
No abstract text is available yet for this article.
February 1, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28175469/108%C3%A2-adverse-events-after-carotid-endarterectomy-a-national-surgical-quality-improvement-program-analysis
#20
Hormuzdiyar H Dasenbrock, Timothy R Smith, William B Gormley, Kai U Frerichs, Mohammad Ali Aziz-Sultan, Rose Du
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
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