Temporal Baseline of Essential and Non-essential Elements Recorded in Baleen of Western Arctic Bowhead Whale (Balaena mysticetus)

This study established the first baseline of changing elemental concentrations in bowhead whale baleen over time (1958–1999). From previously published stable isotope data, year, season (summer or winter), and location (Beaufort or Bering/Chukchi seas) were attributed to each sample. Thirteen elements (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, V, Zn) in baleen from nine subsistence-harvested bowhead whales (n = 138) were detected. Al, Cu, and Fe were the highest concentrations while Cd and V were among the lowest. Our data supports absorption as the main route of exposure to environmental elements rather than biomagnification due to bowhead whales’ low trophic position. A linear mixed-effects model confirmed most elements’ concentrations increased with time, while location and sex were insignificant explanatory factors. These temporal fluctuations were most likely a product of environmental changes due to a warming climate and human activities

Selected plasma fatty acid levels in subsistence fed sled dogs along the Yukon River: a pilot study for biomonitoring

The introduction of the ‘western diet' marked a decline in omega-3 fatty acids rich foods and a concurrent increase in saturated and omega-6 fatty acids that persists today. Historically, circumpolar people have had a low incidence of obesity, diabetes and cardiovascular disease and this has been largely attributed to polyphenolic compounds and omega-3 fatty acids offered from subsistence foods. In this report, we studied sled dogs as an Arctic sentinel species for monitoring the effect of a changing diet on lipid profiles along the Yukon River. Subsistence fed village sled dogs along the Yukon River, maintained largely on salmon were compared with a control kennel maintained on commercial food. Profiles showed higher levels for long chain omega-3 fatty acids in village subsistence fed dogs compared to control dogs and an opposite trend for omega-6 fatty acids, establishing baseline levels for follow up studies. A comparison with data for previously published mercury levels from the same cohort of dogs revealed a positive correlation with alpha-linolenic fatty acid and a negative correlation with linoleic fatty acid. Food and nutritional security is a concern in the Arctic as the impacts of climate change and transport of contaminants become obvious. This study supports not only the nutritional value of a subsistence diet but also the utility of sled dogs as a sentinel for human dietary chang

Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure–activity and structure–property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action

Stable isotope and trace element status of subsistence-hunted bowhead and beluga whales in Alaska and gray whales

Abstract Tissues of bowhead, beluga, and gray whales were analyzed for Ag, Cd, Cu, Se, Zn, THg and MeHg (belugas only). d 15 N and d 13 C in muscle were used to estimate trophic position and feeding habitat, respectively. Trace element concentrations in tissues were significantly different among whale species. Hepatic Ag was higher in belugas than bowheads and gray whales. Gray whales had lower Cd concentrations in liver and kidney than bowhead and belugas and a sigmoid correlation of Cd with length was noted for all whales. Renal and hepatic Se and THg were higher in belugas than in baleen whales. The hepatic molar ratio of Se:THg exceeded 1:1 in all species and was negatively correlated to body length. Hepatic and renal Zn in subsistence-harvested gray whales was lower than concentrations for stranded whales. Se:THg molar ratios and tissue concentrations of Zn may show promise as potential indicators of immune status and animal health

Results from a Fermilab neutrino beam dump experiment

The flux of prompt neutrinos from a beam dump has been measured in an experiment at the Fermi National Accelerator Laboratory (E613). Assuming that the charm production has a linear dependence on atomic number and varies as (1−‖×‖)5 e−2mT, a model dependent cross section of 27±5μb/nucleon can be derived. For neutrino energies greater than 20 GeV, the flux of electron neutrinos with respect to muon neutrinos is 0.78±0.19. For neutrinos with energy greater than 30 GeV and p⟂ greater than 0.2, the flux of ν̄u compared to νμ is 0.96±0.22.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87363/2/100_1.pd

Prompt Neutrino Results from Fermi Lab

Results from a Fermi lab experiment to study prompt neutrino production are presented. Assuming the prompt neutrinos come from the decay of charmed mesons we find a total DD production cross section of approx. 20 μb/nucleon, in good agreement with previous CERN results. We find a ν/ν ratio and a νe/νμ of approx. 1.0. The energy and pT spectra of the prompt neutrinos are consistent with those expected from DD production. Limits on the production of supersymmetric particles have also been obtained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87356/2/262_1.pd

ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 Performance Measures for Adults Undergoing Percutaneous Coronary Intervention A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance

Journal of the American College of Cardiology Ó 2014 by the American College of Cardiology Foundation, American Heart Association, Inc., American Medical Association, and National Committee for Quality Assurance Published by Elsevier Inc. Vol. 63, No. 7, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2013.12.003 PERFORMANCE MEASURES ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 Performance Measures for Adults Undergoing Percutaneous Coronary Intervention A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance Developed in Collaboration With the American Association of Cardiovascular and Pulmonary Rehabilitation and Mended Hearts Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and Mended Hearts WRITING COMMITTEE MEMBERS Brahmajee K. Nallamothu, MD, MPH, FACC, FAHA, Co-Chair*; Carl L. Tommaso, MD, FACC, FAHA, FSCAI, Co-Chairy; H. Vernon Anderson, MD, FACC, FAHA, FSCAI*; Jeffrey L. Anderson, MD, FACC, FAHA, MACP*; Joseph C. Cleveland, J R , MDz; R. Adams Dudley, MD, MBA; Peter Louis Duffy, MD, MMM, FACC, FSCAIy; David P. Faxon, MD, FACC, FAHA*; Hitinder S. Gurm, MD, FACC; Lawrence A. Hamilton, Neil C. Jensen, MHA, MBA; Richard A. Josephson, MD, MS, FACC, FAHA, FAACVPRx; David J. Malenka, MD, FACC, FAHA*; Calin V. Maniu, MD, FACC, FAHA, FSCAIy; Kevin W. McCabe, MD; James D. Mortimer, Manesh R. Patel, MD, FACC*; Stephen D. Persell, MD, MPH; John S. Rumsfeld, MD, PhD, FACC, FAHAjj; Kendrick A. Shunk, MD, PhD, FACC, FAHA, FSCAI*; Sidney C. Smith, J R , MD, FACC, FAHA, FACP{; Stephen J. Stanko, MBA, BA, AA#; Brook Watts, MD, MS *ACC/AHA Representative. ySociety of Cardiovascular Angiography and Interventions Representative. zSociety of Thoracic Surgeons Representative. xAmerican Association of Cardiovascular and Pulmonary Rehabilitation Representative. kACC/AHA Task Force on Performance Measures Liaison. {National Heart Lung and Blood Institute Representative. #Mended Hearts Representative. The measure specifications were approved by the American College of Cardiology Board of Trustees, American Heart Association Science Advisory and Coordinating Committee, in January 2013 and the American Medical Association–Physician Consortium for Performance Improvement in February 2013. This document was approved by the American College of Cardiology Board of Trustees and the American Heart Association Science Advisory and Coordinating Committee in October 2013, and the Society of Cardiovascular Angiography and Interventions in December 2013. The American College of Cardiology requests that this document be cited as follows: Nallamothu BK, Tommaso CL, Anderson HV, Anderson JL, Cleveland JC, Dudley RA, Duffy PL, Faxon DP, Gurm HS, Hamilton LA, Jensen NC, Josephson RA, Malenka DJ, Maniu CV, McCabe KW, Mortimer JD, Patel MR, Persell SD, Rumsfeld JS, Shunk KA, Smith SC, Stanko SJ, Watts B. ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 perfor- mance measures for adults undergoing percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance. J Am Coll Cardiol 2014;63:722–45. This article has been copublished in Circulation. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Asso- ciation (http://my.americanheart.org). For copies of this document, please contact Elsevier Inc. Reprint Department, fax (212) 633-3820, e-mail [email protected]. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site (http://www.elsevier.com/authors/obtaining- permission-to-re-use-elsevier-material). This Physician Performance Measurement Set (PPMS) and related data specifications were developed by the Physician Consortium for Performance Improvement (the Consortium), including the American College of Cardiology (ACC), the American Heart Association (AHA), and the American Medical Association (AMA), to facilitate quality-improvement activities by physicians. The performance measures contained in this PPMS are not clinical guidelines, do not establish a standard of medical care, and have not been tested for all potential applications. Although copyrighted, they can be reproduced and distributed, without modification, for noncommercial purposesdfor example, use by health care pro

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin