Showing papers by "University of Utah published in 2015"
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
The Royal Marsden NHS Foundation Trust1, European Institute of Oncology2, University of Colorado Denver3, Aix-Marseille University4, Baylor University5, University of Michigan6, University of Zurich7, Cross Cancer Institute8, Peter MacCallum Cancer Centre9, Netherlands Cancer Institute10, Hospital General Universitario Gregorio Marañón11, Memorial Sloan Kettering Cancer Center12, Huntsman Cancer Institute13, Yale University14, University of Melbourne15, University of Sydney16, Cornell University17, Ludwig Institute for Cancer Research18, University of Utah19, Yale Cancer Center20, Odense University Hospital21, Bristol-Myers Squibb22, Harvard University23
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
Abstract: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1–negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1–negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)
6,318 citations
Case Western Reserve University1, Wake Forest University2, Tulane University3, National Institutes of Health4, United States Department of Veterans Affairs5, University of Alabama at Birmingham6, University of Tennessee Health Science Center7, University of Colorado Boulder8, Veterans Health Administration9, University of Utah10
TL;DR: In this article, the most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain, and the authors propose a target of less than 120 mm Hg.
Abstract: BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
4,125 citations
Mayo Clinic1, Memorial Sloan Kettering Cancer Center2, Cornell University3, Johns Hopkins University4, University of Utah5, Oregon Health & Science University6, Rutgers University7, University of Pennsylvania8, Fox Chase Cancer Center9, Harvard University10, Bristol-Myers Squibb11, University of California, Los Angeles12
TL;DR: Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma.
Abstract: BACKGROUND Preclinical studies suggest that Reed–Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin’s lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1–blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin’s lymphoma. METHODS In this ongoing study, 23 patients with relapsed or refractory Hodgkin’s lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression. RESULTS Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed–Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling. CONCLUSIONS Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin’s lymphoma. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT01592370.)
3,008 citations
Shadab Alam1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto4 +360 more•Institutions (102)
TL;DR: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrogram, and a novel optical interferometer.
Abstract: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 sq. deg of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-Object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include measured abundances of 15 different elements for each star. In total, SDSS-III added 2350 sq. deg of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 sq. deg; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5,513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.
2,471 citations
TL;DR: A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided in this paper, covering approximately the last seven years, including developments in density functional theory and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces.
Abstract: A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Moller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr_2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.
2,396 citations
Cornell University1, University of Louisville2, New York University3, University of Paris-Sud4, University of Utah5, Harvard University6, Washington University in St. Louis7, Greenville Health System8, University of New Mexico9, Cleveland Clinic10, Duke University11, Oregon Health & Science University12, Bristol-Myers Squibb13, Memorial Sloan Kettering Cancer Center14
TL;DR: The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipILimumab monotherapy.
Abstract: BackgroundIn a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma. MethodsIn this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, we randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivolumab (1 mg per kilogram) or placebo once every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors. ResultsAmong patients with BRAF wild-type tumors, the rate of confirmed objective response was 61% (44 of 72 patients) in the group that received both ipilimumab and ni...
2,370 citations
TL;DR: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults and despite current diagnostic tests, no pathogen was detected in the majority of patients.
Abstract: Background Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. Methods We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. Results From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile ...
2,088 citations
TL;DR: In this article, the authors proposed a nationally recognized licensing framework for AVs, determining appropriate standards for liability, security, and data privacy, which can be used to improve vehicle safety, congestion, and travel behavior.
Abstract: Autonomous vehicles (AVs) represent a potentially disruptive yet beneficial change to our transportation system. This new technology has the potential to impact vehicle safety, congestion, and travel behavior. All told, major social AV impacts in the form of crash savings, travel time reduction, fuel efficiency and parking benefits are estimated to approach $2000 to per year per AV, and may eventually approach nearly $4000 when comprehensive crash costs are accounted for. Yet barriers to implementation and mass-market penetration remain. Initial costs will likely be unaffordable. Licensing and testing standards in the U.S. are being developed at the state level, rather than nationally, which may lead to inconsistencies across states. Liability details remain undefined, security concerns linger, and without new privacy standards, a default lack of privacy for personal travel may become the norm. The impacts and interactions with other components of the transportation system, as well as implementation details, remain uncertain. To address these concerns, the federal government should expand research in these areas and create a nationally recognized licensing framework for AVs, determining appropriate standards for liability, security, and data privacy.
2,053 citations
TL;DR: It is recommended that qualitative researchers return to the terminology of social sciences, using rigor, reliability, validity, and generalizability, and make recommendations for the appropriate use of the strategies recommended to achieve rigor.
Abstract: Criteria for determining the trustworthiness of qualitative research were introduced by Guba and Lincoln in the 1980s when they replaced terminology for achieving rigor, reliability, validity, and generalizability with dependability, credibility, and transferability. Strategies for achieving trustworthiness were also introduced. This landmark contribution to qualitative research remains in use today, with only minor modifications in format. Despite the significance of this contribution over the past four decades, the strategies recommended to achieve trustworthiness have not been critically examined. Recommendations for where, why, and how to use these strategies have not been developed, and how well they achieve their intended goal has not been examined. We do not know, for example, what impact these strategies have on the completed research. In this article, I critique these strategies. I recommend that qualitative researchers return to the terminology of social sciences, using rigor, reliability, validity, and generalizability. I then make recommendations for the appropriate use of the strategies recommended to achieve rigor: prolonged engagement, persistent observation, and thick, rich description; inter-rater reliability, negative case analysis; peer review or debriefing; clarifying researcher bias; member checking; external audits; and triangulation.
Charité1, Max Planck Society2, University of Rome Tor Vergata3, University of Würzburg4, Istanbul University5, University of Utah6, Hospital Universitario La Paz7, Carlos III Health Institute8, Lawrence Berkeley National Laboratory9, University of California, Merced10, United States Department of Energy11
TL;DR: The results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.
10 Aug 2015
TL;DR: This work links disparate impact to a measure of classification accuracy that while known, has received relatively little attention and proposes a test for disparate impact based on how well the protected class can be predicted from the other attributes.
Abstract: What does it mean for an algorithm to be biased? In U.S. law, unintentional bias is encoded via disparate impact, which occurs when a selection process has widely different outcomes for different groups, even as it appears to be neutral. This legal determination hinges on a definition of a protected class (ethnicity, gender) and an explicit description of the process.When computers are involved, determining disparate impact (and hence bias) is harder. It might not be possible to disclose the process. In addition, even if the process is open, it might be hard to elucidate in a legal setting how the algorithm makes its decisions. Instead of requiring access to the process, we propose making inferences based on the data it uses.We present four contributions. First, we link disparate impact to a measure of classification accuracy that while known, has received relatively little attention. Second, we propose a test for disparate impact based on how well the protected class can be predicted from the other attributes. Third, we describe methods by which data might be made unbiased. Finally, we present empirical evidence supporting the effectiveness of our test for disparate impact and our approach for both masking bias and preserving relevant information in the data. Interestingly, our approach resembles some actual selection practices that have recently received legal scrutiny.
Memorial Sloan Kettering Cancer Center1, University of Lausanne2, Rutgers University3, University of North Carolina at Chapel Hill4, Harvard University5, University of Southern California6, Broad Institute7, Washington University in St. Louis8, Buck Institute for Research on Aging9, University of British Columbia10, Van Andel Institute11, The Chinese University of Hong Kong12, University of Utah13, Stanford University14, University of California, San Francisco15, United States Department of Veterans Affairs16, University of Pittsburgh17, University of Texas MD Anderson Cancer Center18, BC Cancer Agency19
TL;DR: This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options, suggesting differential modulation of ER activity in I LC and IDC.
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
Book•
30 Jan 2015TL;DR: The second edition of The Great Psychotherapy Debate has been updated and revised to expand the presentation of the Contextual Model, which is derived from a scientific understanding of how humans heal in a social context and explains findings from a vast array of psychotherapies studies as discussed by the authors.
Abstract: The second edition of The Great Psychotherapy Debate has been updated and revised to expand the presentation of the Contextual Model, which is derived from a scientific understanding of how humans heal in a social context and explains findings from a vast array of psychotherapies studies. This model provides a compelling alternative to traditional research on psychotherapy, which tends to focus on identifying the most effective treatment for particular disorders through emphasizing the specific ingredients of treatment. The new edition also includes a history of healing practices, medicine, and psychotherapy, an examination of therapist effects, and a thorough review of the research on common factors such as the alliance, expectations, and empathy.
TL;DR: This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.
École Polytechnique Fédérale de Lausanne1, Paris Diderot University2, University of California, Irvine3, Lawrence Berkeley National Laboratory4, Brookhaven National Laboratory5, Max Planck Society6, University of Portsmouth7, New Mexico State University8, University of Utah9, Harvard University10, University of Barcelona11, Aix-Marseille University12, University of Wyoming13, Pierre-and-Marie-Curie University14, Carnegie Mellon University15, Institut d'Astrophysique de Paris16, Drexel University17, Sejong University18, Pennsylvania State University19, Ohio State University20, University of Chicago21
TL;DR: In this paper, a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations was reported.
Abstract: We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations The study uses 137,562 quasars in the redshift range 2:1 z 3:5 from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III This sample contains three times the number of quasars used in previous studies The measured position of the BAO peak determines the angular distance, DA(z = 2:34) and expansion rate, H(z = 2:34), both on a scale set by the sound horizon at the drag epoch, rd We find DA=rd =
Boston Children's Hospital1, German Cancer Research Center2, University of Texas MD Anderson Cancer Center3, St. Jude Children's Research Hospital4, University of Toronto5, Max Planck Society6, Heidelberg University7, University of Utah8, Tel Aviv University9, University of Colorado Denver10, University of Bern11, Masaryk University12, University of Texas Health Science Center at San Antonio13, University of California, San Francisco14, New York University15, University of Cambridge16, University of Hamburg17, University of Bonn18
TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
Duke University1, Columbia University2, University of Massachusetts Medical School3, McGill University4, Stanford University5, Biogen Idec6, Harvard University7, Washington University in St. Louis8, University of Amsterdam9, Trinity College, Dublin10, King's College London11, Utrecht University12, University of Milan13, Cedars-Sinai Medical Center14, Cornell University15, University of California, San Diego16, University of Utah17, University of Pennsylvania18, Emory University19
TL;DR: A moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS found several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene.
Abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.
TL;DR: This update of a 2007 guideline from the American Academy of Otolaryngology—Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity.
Abstract: ObjectiveThis update of a 2007 guideline from the American Academy of Otolaryngology—Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS).PurposeThe purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing adult rhinosinusitis and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy for adu...
University of Utah1, Northern Arizona University2, University of Nevada, Reno3, Spanish National Research Council4, University of New Mexico5, Arizona State University6, United States Forest Service7, National Oceanic and Atmospheric Administration8, Lamont–Doherty Earth Observatory9, Princeton University10
TL;DR: P pervasive and substantial “legacy effects” of reduced growth and incomplete recovery for 1 to 4 years after severe drought were found, most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins.
Abstract: The impacts of climate extremes on terrestrial ecosystems are poorly understood but important for predicting carbon cycle feedbacks to climate change. Coupled climate-carbon cycle models typically assume that vegetation recovery from extreme drought is immediate and complete, which conflicts with the understanding of basic plant physiology. We examined the recovery of stem growth in trees after severe drought at 1338 forest sites across the globe, comprising 49,339 site-years, and compared the results with simulated recovery in climate-vegetation models. We found pervasive and substantial "legacy effects" of reduced growth and incomplete recovery for 1 to 4 years after severe drought. Legacy effects were most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins. In contrast, limited or no legacy effects after drought were simulated by current climate-vegetation models. Our results highlight hysteresis in ecosystem-level carbon cycling and delayed recovery from climate extremes.
TL;DR: This commentary considers the amassed evidence that shows that self-report dietary intake data can successfully be used to inform dietary guidance and public health policy and 7 specific recommendations for collecting, analyzing, and interpreting self- report dietary data are provided.
Abstract: Recent reports have asserted that, because of energy underreporting, dietary self-report data suffer from measurement error so great that findings that rely on them are of no value. This commentary considers the amassed evidence that shows that self-report dietary intake data can successfully be used to inform dietary guidance and public health policy. Topics discussed include what is known and what can be done about the measurement error inherent in data collected by using self-report dietary assessment instruments and the extent and magnitude of underreporting energy compared with other nutrients and food groups. Also discussed is the overall impact of energy underreporting on dietary surveillance and nutritional epidemiology. In conclusion, 7 specific recommendations for collecting, analyzing, and interpreting self-report dietary data are provided: (1) continue to collect self-report dietary intake data because they contain valuable, rich, and critical information about foods and beverages consumed by populations that can be used to inform nutrition policy and assess diet-disease associations; (2) do not use self-reported energy intake as a measure of true energy intake; (3) do use self-reported energy intake for energy adjustment of other self-reported dietary constituents to improve risk estimation in studies of diet-health associations; (4) acknowledge the limitations of self-report dietary data and analyze and interpret them appropriately; (5) design studies and conduct analyses that allow adjustment for measurement error; (6) design new epidemiologic studies to collect dietary data from both short-term (recalls or food records) and long-term (food-frequency questionnaires) instruments on the entire study population to allow for maximizing the strengths of each instrument; and (7) continue to develop, evaluate, and further expand methods of dietary assessment, including dietary biomarkers and methods using new technologies.
TL;DR: An international group of cancer geneticists review the level of evidence for the association of gene variants with the risk of breast cancer and it is difficult to draw firm conclusions from the data because of ascertainment bias and the lack of data from large populations.
Abstract: An international group of cancer geneticists review the level of evidence for the association of gene variants with the risk of breast cancer. It is difficult to draw firm conclusions from the data because of ascertainment bias and the lack of data from large populations.
University of Utah1, Baylor College of Medicine2, University of North Carolina at Chapel Hill3, National Institutes of Health4, University of Toronto5, Boston Children's Hospital6, Johns Hopkins University7, Stanford University8, Cincinnati Children's Hospital Medical Center9, University of Pennsylvania10, Seattle Children's11, American Society of Human Genetics12
TL;DR: This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children and a broad range of test technologies and their applications in clinical medicine and research.
Abstract: In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education.
TL;DR: An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed.
Abstract: Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs) in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β) signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curacao) diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed.
TL;DR: In this paper, the authors examined the relationship between the quality of a firm's voluntary environmental disclosure and its expected future cash flows and the cost of equity, and found that the type and nature of the environmental disclosure is informative in establishing the predicted relations.
Icahn School of Medicine at Mount Sinai1, University of Connecticut2, Baylor University Medical Center3, Northwestern University4, Autonomous University of Barcelona5, University of Colorado Denver6, Medical University of Vienna7, Harvard University8, University of Paris9, Kaiser Permanente10, Dalhousie University11, Paul Sabatier University12, Centre Hospitalier Universitaire de Nice13, University of Texas Health Science Center at Houston14, University of Rome Tor Vergata15, University of Utah16, University of California, San Francisco17, Amgen18
TL;DR: Bdalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis, and was found to be superior to placebo at week 12 with respect to a 100% reduction in PASI score (PASI 100).
Abstract: BackgroundEarly clinical studies suggested that the anti–interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. MethodsIn two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician’s global assessment ...
TL;DR: In this paper, the authors used an inverse design algorithm and experimentally demonstrated an integrated polarization beamsplitter with a footprint of 2.4×××2.4 μm2.
Abstract: Researchers used an inverse design algorithm and experimentally demonstrated an integrated polarization beamsplitter with a footprint of 2.4 × 2.4 μm2.