Showing papers by "University of Kansas published in 2015"
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North Carolina State University1, Michigan State University2, Centre national de la recherche scientifique3, University of Colorado Boulder4, McGill University5, University of Florida6, George Mason University7, University of Maryland, College Park8, Commonwealth Scientific and Industrial Research Organisation9, Colby College10, St. Cloud State University11, University of Wisconsin-Madison12, Imperial College London13, University of Kansas14, James Cook University15, National Science Foundation16, University of Indonesia17, Charles Sturt University18
TL;DR: An analysis of global forest cover is conducted to reveal that 70% of remaining forest is within 1 km of the forest’s edge, subject to the degrading effects of fragmentation, indicating an urgent need for conservation and restoration measures to improve landscape connectivity.
Abstract: We conducted an analysis of global forest cover to reveal that 70% of remaining forest is within 1 km of the forest’s edge, subject to the degrading effects of fragmentation. A synthesis of fragmentation experiments spanning multiple biomes and scales, five continents, and 35 year sd emonstrates that habitatfragmentation reduces biodiversity by 13 to 75% and impairs key ecosystem functions by decreasing biomass and altering nutrient cycles. Effects are greatest in the smallest and most isolated fragments, and they magnify with the passage of time. These findings indicate an urgent need for conservation and restoration measures to improve landscape connectivity, which will reduce extinction rates and help maintain ecosystem services.
2,201 citations
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TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
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TL;DR: Associations between inherited cellular transport gene variants and risk of EOC histologic subtypes are revealed on a large cohort of women.
Abstract: BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
1,100 citations
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TL;DR: Mortality among persons with type 2 diabetes, as compared with that in the general population, varied greatly, from substantial excess risks in large patient groups to lower risks of death depending on age, glycemic control, and renal complications.
Abstract: BackgroundThe excess risks of death from any cause and death from cardiovascular causes among persons with type 2 diabetes and various levels of glycemic control and renal complications are unknown. In this registry-based study, we assessed these risks according to glycemic control and renal complications among persons with type 2 diabetes. MethodsWe included patients with type 2 diabetes who were registered in the Swedish National Diabetes Register on or after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. All the participants were followed until December 31, 2011, in the Swedish Registry for Cause-Specific Mortality. ResultsThe mean follow-up was 4.6 years in the diabetes group and 4.8 years in the control group. Overall, 77,117 of 435,369 patients with diabetes (17.7%) died, as compared with 306,097 of 2,117,483 controls (14.5%) (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.14 to 1.16). T...
708 citations
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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam +2134 more•Institutions (142)
TL;DR: The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays, and no significant deviations are found.
Abstract: Properties of the Higgs boson with mass near 125 GeV are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include gamma gamma, ZZ, WW, tau tau, bb, and mu mu pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1 inverse femtobarns at 7 TeV and up to 19.7 inverse femtobarns at 8 TeV. From the high-resolution gamma gamma and ZZ channels, the mass of the Higgs boson is determined to be 125.02 +0.26 -0.27 (stat) +0.14 -0.15 (syst) GeV. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is 1.00 +/- 0.09 (stat) +0.08 -0.07 (theo) +/- 0.07 (syst) at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.
677 citations
Primary Children's Hospital1, University of Colorado Denver2, Northwestern University3, Georgetown University4, University of Washington5, Columbia University6, University of North Carolina at Chapel Hill7, University of California, San Francisco8, Baylor University Medical Center9, Mayo Clinic10, University of California, San Diego11, University of Miami12, Johns Hopkins University13, University of Kansas14, Henry Ford Health System15, Indiana University16, Washington University in St. Louis17, Duke University18, New York University19, University of Michigan20, University of Pennsylvania21, Harvard University22
TL;DR: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation.
Abstract: Background & Aims There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. Methods In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). Results We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%–89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%–98% of patients without cirrhosis or with compensated cirrhosis, by 85%−88% of patients with moderate hepatic impairment, by 60%–75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. Conclusion The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430.
670 citations
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Primary Children's Hospital1, University of Colorado Denver2, Northwestern University3, Georgetown University4, University of Washington5, Columbia University6, University of North Carolina at Chapel Hill7, University of California, San Francisco8, Baylor University Medical Center9, Mayo Clinic10, University of California, San Diego11, University of Miami12, Johns Hopkins University13, University of Kansas14, Henry Ford Health System15, Indiana University16, Washington University in St. Louis17, Duke University18, New York University19, University of Michigan20, University of Pennsylvania21, Harvard University22
TL;DR: In this article, the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin were used to treat chronic hepatitis C virus (HCV) infection in patients with advanced liver disease.
659 citations
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TL;DR: This review discusses the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion and mitochondrial motility in mitophagy, and discusses multiple pathways leading to the quality control of mitochondria in addition to the traditionalMitophagy pathway under different conditions.
Abstract: Mitochondria are cellular energy powerhouses that play important roles in maintaining cell survival, cell death and cellular metabolic homeostasis. Timely removal of damaged mitochondria via autophagy (mitophagy) is thus critical for cellular homeostasis and function. Mitochondria are reticular organelles that have high plasticity for their dynamic structures and constantly undergo fission and fusion as well as movement through the cytoskeleton. In this review, we discuss the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion and mitochondrial motility in mitophagy. We also discuss multiple pathways leading to the quality control of mitochondria in addition to the traditional mitophagy pathway under different conditions.
600 citations
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TL;DR: This study is the first, to the knowledge, to apply an efficient and automated process for assembling published trees into a complete tree of life, and presents a draft tree containing 2.3 million tips—the Open Tree of Life.
Abstract: Reconstructing the phylogenetic relationships that unite all lineages (the tree of life) is a grand challenge. The paucity of homologous character data across disparately related lineages currently renders direct phylogenetic inference untenable. To reconstruct a comprehensive tree of life, we therefore synthesized published phylogenies, together with taxonomic classifications for taxa never incorporated into a phylogeny. We present a draft tree containing 2.3 million tips-the Open Tree of Life. Realization of this tree required the assembly of two additional community resources: (i) a comprehensive global reference taxonomy and (ii) a database of published phylogenetic trees mapped to this taxonomy. Our open source framework facilitates community comment and contribution, enabling the tree to be continuously updated when new phylogenetic and taxonomic data become digitally available. Although data coverage and phylogenetic conflict across the Open Tree of Life illuminate gaps in both the underlying data available for phylogenetic reconstruction and the publication of trees as digital objects, the tree provides a compelling starting point for community contribution. This comprehensive tree will fuel fundamental research on the nature of biological diversity, ultimately providing up-to-date phylogenies for downstream applications in comparative biology, ecology, conservation biology, climate change, agriculture, and genomics.
556 citations
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Indiana University1, Indiana University – Purdue University Indianapolis2, University of Minnesota3, Emory University4, University of Kansas5, Cornell University6, Thomas Jefferson University7, Marshfield Clinic8, United States Department of Veterans Affairs9, University of California, Los Angeles10, St. Joseph's Hospital and Medical Center11, Stanford University12, New York University13, University of Pennsylvania14, University of California, San Francisco15, University of Virginia16, Sinai University17, Medtronic plc18
TL;DR: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.
Abstract: Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators9 discretion. Seizure frequency was determined using daily seizure diaries. Results: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years ( p Conclusion: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.
545 citations
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University of Texas MD Anderson Cancer Center1, Medical College of Wisconsin2, Northside Hospital3, Fred Hutchinson Cancer Research Center4, University of Kansas5, Harvard University6, Ohio State University7, National Institutes of Health8, Johns Hopkins University9, City of Hope National Medical Center10, Memorial Sloan Kettering Cancer Center11, University of Pennsylvania12, Karolinska Institutet13, Churchill Hospital14, Washington University in St. Louis15, University of Minnesota16
TL;DR: It is suggested that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation.
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Mayo Clinic1, University of Kansas2, Ohio State University3, Harvard University4, Ludwig Maximilian University of Munich5, University of California, Los Angeles6, University of Erlangen-Nuremberg7, University of Ulm8, Aristotle University of Thessaloniki9, University of Helsinki10, University of Southampton11, University of Sheffield12, University of Tübingen13, Roswell Park Cancer Institute14
TL;DR: Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCa2.
Abstract: Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P .001) and had higher-grade tumors (P .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. J Clin Oncol 33:304-311. © 2014 by American Society of Clinical Oncology
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TL;DR: In this article, the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis are combined, and the combined event sample features high-statistics samples of shower-like and track-like events.
Abstract: Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for neutrino events with deposited energies greater than or similar to 30 TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, nu(mu)-induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index -2.50 +/- 0.09 and a flux at 100 TeV of (6.7(-1.2)(+1.1)) x 10(-18) GeV-1 s(-1) sr(-1) cm(-2). Under the same assumptions, an unbroken power law with index -2 is disfavored with a significance of 3.8 sigma (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 sigma (p = 1.7%) if instead we compare the best fit to a spectrum with index -2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a nu(e) fraction of 0.18 +/- 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 sigma ( p = 0.014%).
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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2 +2802 more•Institutions (215)
TL;DR: In this paper, the branching fractions of the B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) were observed.
Abstract: The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.
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University of Copenhagen1, University of California, Berkeley2, University of Massachusetts Amherst3, Wellcome Trust Sanger Institute4, Technical University of Denmark5, Pennsylvania State University6, La Trobe University7, Stanford University8, King Abdullah University of Science and Technology9, University of Cambridge10, University of Tartu11, Estonian Biocentre12, University of California, San Francisco13, Washington State University14, University of Porto15, University of Illinois at Urbana–Champaign16, Carlos III Health Institute17, University of Utah18, Science for Life Laboratory19, Aarhus University20, University College London21, University of Reading22, University of Bristol23, University of Guadalajara24, University of Bologna25, Oregon State University26, University of Paris27, University of Zurich28, Max Planck Society29, St. John's University30, University of California, Irvine31, University of Tarapacá32, University of Toulouse33, Novosibirsk State University34, Russian Academy of Sciences35, Kemerovo State University36, Bashkir State University37, North-Eastern Federal University38, Western Washington University39, Northwest Community College40, Simon Fraser University41, University of Western Ontario42, Laboratory of Molecular Biology43, University of Kansas44, University of California, Davis45, Texas A&M University46, Santa Barbara Museum of Natural History47, Southern Methodist University48
TL;DR: The results suggest that there has been gene flow between some Native Americans from both North and South America and groups related to East Asians and Australo-Melanesians, the latter possibly through an East Asian route that might have included ancestors of modern Aleutian Islanders.
Abstract: How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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01 Jan 2015
TL;DR: A number of possible approaches to the nature of the spectrum congestion problem from a radar perspective are described, and these include improved transmitter spectral purity, passive radar, and intelligent, cognitive approaches that dynamically optimize spectrum use.
Abstract: The radio-frequency (RF) electromagnetic spectrum, extending from below 1 MHz to above 100 GHz, represents a precious resource. It is used for a wide range of purposes, including communications, radio and television broadcasting, radionavigation, and sensing. Radar represents a fundamentally important use of the electromagnetic (EM) spectrum, in applications which include air traffic control, geophysical monitoring of Earth resources from space, automotive safety, severe weather tracking, and surveillance for defense and security. Nearly all services have a need for greater bandwidth, which means that there will be ever-greater competition for this finite resource. The paper explains the nature of the spectrum congestion problem from a radar perspective, and describes a number of possible approaches to its solution both from technical and regulatory points of view. These include improved transmitter spectral purity, passive radar, and intelligent, cognitive approaches that dynamically optimize spectrum use.
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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2 +2119 more•Institutions (141)
TL;DR: In this paper, a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum was conducted at the LHC.
Abstract: Results are presented from a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum. The data were collected by the CMS detector in proton-proton collisions at the LHC and correspond to an integrated luminosity of 19.7 fb$^{-1}$ at a centre-of-mass energy of 8 TeV. The number of observed events is found to be consistent with the standard model prediction. Limits are placed on the DM-nucleon scattering cross section as a function of the DM particle mass for spin-dependent and spin-independent interactions. Limits are also placed on the scale parameter $M_\mathrm{D}$ in the ADD model of large extra dimensions, and on the unparticle model parameter $\Lambda_\mathrm{U}$. The constraints on ADD models and unparticles are the most stringent limits in this channel and those on the DM-nucleon scattering cross section are an improvement over previous collider results.
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TL;DR: Updated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.
Abstract: Introduction
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65–75 % of cases), maternal uniparental disomy 15 (20–30 % of cases), and imprinting defect (1–3 %). DNA methylation analysis is the only technique that will diagnose PWS in all three molecular genetic classes and differentiate PWS from Angelman syndrome. Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking with excessive weight gain, developmental delay, cognitive disability and behavioral problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS.
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TL;DR: Genomic comparison with B. thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet.
Abstract: Yeasts, which have been a component of the human diet for at least 7,000 years, possess an elaborate cell wall α-mannan The influence of yeast mannan on the ecology of the human microbiota is unknown Here we show that yeast α-mannan is a viable food source for the Gram-negative bacterium Bacteroides thetaiotaomicron, a dominant member of the microbiota Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes Co-culturing studies showed that metabolism of yeast mannan by B thetaiotaomicron presents a 'selfish' model for the catabolism of this difficult to breakdown polysaccharide Genomic comparison with B thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet
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National Institutes of Health1, University of Vermont2, University of North Carolina at Chapel Hill3, Cincinnati Children's Hospital Medical Center4, New York University5, Michigan State University6, University of California, San Francisco7, University of Wisconsin-Madison8, Baylor College of Medicine9, Yale University10, University of Missouri11, University of Kansas12, Washington State University13, Harvard University14
TL;DR: Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success.
Abstract: Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success.
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TL;DR: A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients.
Abstract: The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A–1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A–1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.
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TL;DR: An overview of the defining features, design variations, strengths, and weaknesses of vignette studies as a way of examining how health professionals form clinical judgments and how they are being used to investigate clinicians’ diagnostic decisions in case-controlled field studies for the ICD-11 classification of mental and behavioural disorders.
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Vardan Khachatryan, Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1 +2114 more•Institutions (146)
TL;DR: In this article, the spin-parity and tensor structure of the interactions of the recently discovered Higgs boson is performed using the H to ZZ, Z gamma*, gamma* gamma* to 4 l, H to WW to l nu l nu, and H to gamma gamma decay modes.
Abstract: The study of the spin-parity and tensor structure of the interactions of the recently discovered Higgs boson is performed using the H to ZZ, Z gamma*, gamma* gamma* to 4 l, H to WW to l nu l nu, and H to gamma gamma decay modes. The full dataset recorded by the CMS experiment during the LHC Run 1 is used, corresponding to an integrated luminosity of up to 5.1 inverse femtobarns at a center-of-mass energy of 7 TeV and up to 19.7 inverse femtobarns at 8 TeV. A wide range of spin-two models is excluded at a 99% confidence level or higher, or at a 99.87% confidence level for the minimal gravity-like couplings, regardless of whether assumptions are made on the production mechanism. Any mixed-parity spin-one state is excluded in the ZZ and WW modes at a greater than 99.999% confidence level. Under the hypothesis that the resonance is a spin-zero boson, the tensor structure of the interactions of the Higgs boson with two vector bosons ZZ, Z gamma, gamma gamma, and WW is investigated and limits on eleven anomalous contributions are set. Tighter constraints on anomalous HVV interactions are obtained by combining the HZZ and HWW measurements. All observations are consistent with the expectations for the standard model Higgs boson with the quantum numbers J[PC]=0[++].
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Louisiana State University1, Aarhus University Hospital2, University of California, Los Angeles3, Saarland University4, Haukeland University Hospital5, Helsinki University Central Hospital6, Wills Eye Institute7, University of Pittsburgh8, Yonsei University9, University of Kansas10, Vision Institute11, Tufts University12, Kyoto Prefectural University of Medicine13, University of Mainz14
TL;DR: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophy more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one cornean layer.
Abstract: Purpose:To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information.Methods:The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this
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TL;DR: Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin.
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TL;DR: Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year, which is associated with improved transplant-free survival, independent of heart failure severity.
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Cleveland Clinic1, Fred Hutchinson Cancer Research Center2, Peter MacCallum Cancer Centre3, University of Sydney4, Mater Health Services5, Fox Chase Cancer Center6, Harvard University7, University of Southern California8, University of Washington9, University of Kansas10, National Institutes of Health11, University of California, Irvine12, University of Texas MD Anderson Cancer Center13, Loyola University Chicago14
TL;DR: Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility.
Abstract: BackgroundOvarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. MethodsWe randomly assigned 257 premenopausal women with operable hormone-receptor–negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. ResultsAt baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate wa...
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TL;DR: Compared to aqueous eDNA, sedimentary eDNA could provide a more abundant and longer-lasting source of genetic material for inferring current-or-past site occupancy by aquatic macrofauna, particularly benthic species, however, resuspension and transport of sedimentaryeDNA could complicate the spatiotemporal inferences from surface water sampling, which is currently the predominant eDNA-based approach.
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TL;DR: In 2011, the American Cancer Society and the American Society for Colposcopy and Cervical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors.
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Houston Methodist Hospital1, Mount Sinai Health System2, Riverside Methodist Hospital3, The Texas Heart Institute4, University of Michigan5, University of Pittsburgh6, Spectrum Health7, University of Kansas8, Saint Francis University9, Duke University10, PinnacleHealth System11, Johns Hopkins University12, Kaiser Permanente13, Mayo Clinic14, Medtronic plc15, Harvard University16
TL;DR: In patients with severe aortic stenosis who are at increased surgical risk, the higher rate of survival with a self-expanding TAVR compared with surgery was sustained at 2 years.