Showing papers by "University of Minnesota published in 2012"
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TL;DR: In this paper, results from searches for the standard model Higgs boson in proton-proton collisions at 7 and 8 TeV in the CMS experiment at the LHC, using data samples corresponding to integrated luminosities of up to 5.8 standard deviations.
8,857 citations
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University of Michigan1, College of William & Mary2, McGill University3, Western Washington University4, Arizona State University5, Imperial College London6, University of Minnesota7, Swedish University of Agricultural Sciences8, Stanford University9, Centre national de la recherche scientifique10, United States Geological Survey11, University of British Columbia12, Columbia University13
TL;DR: It is argued that human actions are dismantling the Earth’s ecosystems, eliminating genes, species and biological traits at an alarming rate, and the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper is asked.
Abstract: The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.
5,244 citations
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Tohoku University1, University of Zurich2, Lawrence Berkeley National Laboratory3, Stanford University4, College of William & Mary5, University of Genoa6, University of Urbino7, CERN8, Budker Institute of Nuclear Physics9, University of California, Irvine10, Cornell University11, Argonne National Laboratory12, ETH Zurich13, Tata Institute of Fundamental Research14, Hillsdale College15, Spanish National Research Council16, Ohio State University17, University of Notre Dame18, Kent State University19, University of California, San Diego20, University of California, Berkeley21, University of Minnesota22, University of Alabama23, University of Helsinki24, Los Alamos National Laboratory25, California Institute of Technology26, George Washington University27, Syracuse University28, Lawrence Livermore National Laboratory29, Oklahoma State University–Stillwater30, University of Washington31, Max Planck Society32, Boston University33, University of California, Los Angeles34, Royal Holloway, University of London35, Université Paris-Saclay36, Fermilab37, University of Pennsylvania38, University of Illinois at Urbana–Champaign39, University of Bristol40, University of Tokyo41, University of Delaware42, Carnegie Mellon University43, University of California, Santa Cruz44, Karlsruhe Institute of Technology45, Heidelberg University46, Florida State University47, Carleton University48, University of Mainz49, University of Edinburgh50, Brookhaven National Laboratory51, Durham University52, University of Lausanne53, Massachusetts Institute of Technology54, University of Southampton55, Nagoya University56, University of Oxford57, Northwestern University58, University of British Columbia59, Columbia University60, Lund University61, University of Sheffield62, University of California, Santa Barbara63, Iowa State University64, University of Alberta65, University of Cambridge66
TL;DR: The Particle Data Group's biennial review as mentioned in this paper summarizes much of particle physics, using data from previous editions, plus 2658 new measurements from 644 papers, and lists, evaluates, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons.
Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, V-cb & V-ub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.
4,465 citations
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Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
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University of Florida1, Veterans Health Administration2, University of Chicago3, University of Minnesota4, University of Washington5, University of Pennsylvania6, Case Western Reserve University7, University of Arizona8, Harvard University9, University of Southern California10, American Academy of Sleep Medicine11
TL;DR: The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography, and recommended scoring rules.
Abstract: The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions.The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO(2) signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults.The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO(2) are the end-tidal PCO(2) or transcutaneous PCO(2) (diagnostic study) or transcutaneous PCO(2) (titration study). For adults, sleep hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO(2) (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring.
3,888 citations
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TL;DR: The combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease.
Abstract: A b s t r ac t Background Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. Methods Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials. Results Mean measured GFRs were 68 and 70 ml per minute per 1.73 m 2 of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m 2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m 2 with the creatinine equation and the cystatin C equation (P = 0.07 and P = 0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m 2 , respectively [P = 0.001 and P 30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m 2 , the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m 2 or greater than or equal to 60 ml per minute per 1.73 m 2 (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m 2 as having a GFR of 60 ml or higher per minute per 1.73 m 2 . Conclusions The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)
2,980 citations
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TL;DR: This version of the SOC recognizes that treatment for gender dysphoria has become more individualized, and can be used to help patients consider the full range of health services open to them, in accordance with their clinical needs and goals for gender expression.
Abstract: The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts ...
2,762 citations
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TL;DR: It is concluded that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses, and fundamental changes in chemical testing and safety determination are needed to protect human health.
Abstract: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...
2,475 citations
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TL;DR: This work presents a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples.
Abstract: Background: There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls. Results: Here we present a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations (e.g. cases and controls) using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples. We validate the fundamental idea in a cell mixture reconstruction experiment, then demonstrate our method on DNA methylation data sets from several studies, including data from a Head and Neck Squamous Cell Carcinoma (HNSCC) study and an ovarian cancer study. Our method produces results consistent with prior biological findings, thereby validating the approach. Conclusions: Our method, in combination with an appropriate external validation set, promises new opportunities for large-scale immunological studies of both disease states and noxious exposures.
2,431 citations
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TL;DR: A global-scale assessment of intensification prospects from closing ‘yield gaps’, the spatial patterns of agricultural management practices and yield limitation, and the management changes that may be necessary to achieve increased yields finds that global yield variability is heavily controlled by fertilizer use, irrigation and climate.
Abstract: In the coming decades, a crucial challenge for humanity will be meeting future food demands without undermining further the integrity of the Earth’s environmental systems1, 2, 3, 4, 5, 6. Agricultural systems are already major forces of global environmental degradation4, 7, but population growth and increasing consumption of calorie- and meat-intensive diets are expected to roughly double human food demand by 2050 (ref. 3). Responding to these pressures, there is increasing focus on ‘sustainable intensification’ as a means to increase yields on underperforming landscapes while simultaneously decreasing the environmental impacts of agricultural systems2, 3, 4, 8, 9, 10, 11. However, it is unclear what such efforts might entail for the future of global agricultural landscapes. Here we present a global-scale assessment of intensification prospects from closing ‘yield gaps’ (differences between observed yields and those attainable in a given region), the spatial patterns of agricultural management practices and yield limitation, and the management changes that may be necessary to achieve increased yields. We find that global yield variability is heavily controlled by fertilizer use, irrigation and climate. Large production increases (45% to 70% for most crops) are possible from closing yield gaps to 100% of attainable yields, and the changes to management practices that are needed to close yield gaps vary considerably by region and current intensity. Furthermore, we find that there are large opportunities to reduce the environmental impact of agriculture by eliminating nutrient overuse, while still allowing an approximately 30% increase in production of major cereals (maize, wheat and rice). Meeting the food security and sustainability challenges of the coming decades is possible, but will require considerable changes in nutrient and water management.
2,099 citations
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TL;DR: Applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step are discussed.
Abstract: Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.
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TL;DR: The Human Connectome Project (HCP) as discussed by the authors is a 5-year effort to characterize brain connectivity and function and their variability in healthy adults using diffusion imaging (dMRI), resting-state fMRI, task-evoked fMRI (T-fMRI), T1-and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography (MEG/EEG).
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TL;DR: In this article, the authors quantified the biomass allocation patterns to leaves, stems and roots in vegetative plants, and how this is influenced by the growth environment, plant size, evolutionary history and competition.
Abstract: Contents
Summary 30
I. Allocation in perspective 31
II. Topics of this review 32
III. Methodology 32
IV. Environmental effects 33
V. Ontogeny 36
VI. Differences between species 40
VII. Physiology and molecular regulation 41
VIII. Ecological aspects 42
IX. Perspectives 45
Acknowledgements 45
References 45
Appendices A1–A4 49
Summary
We quantified the biomass allocation patterns to leaves, stems and roots in vegetative plants, and how this is influenced by the growth environment, plant size, evolutionary history and competition. Dose–response curves of allocation were constructed by means of a meta-analysis from a wide array of experimental data. They show that the fraction of whole-plant mass represented by leaves (LMF) increases most strongly with nutrients and decreases most strongly with light. Correction for size-induced allocation patterns diminishes the LMF-response to light, but makes the effect of temperature on LMF more apparent. There is a clear phylogenetic effect on allocation, as eudicots invest relatively more than monocots in leaves, as do gymnosperms compared with woody angiosperms. Plants grown at high densities show a clear increase in the stem fraction. However, in most comparisons across species groups or environmental factors, the variation in LMF is smaller than the variation in one of the other components of the growth analysis equation: the leaf area : leaf mass ratio (SLA). In competitive situations, the stem mass fraction increases to a smaller extent than the specific stem length (stem length : stem mass). Thus, we conclude that plants generally are less able to adjust allocation than to alter organ morphology.
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Andrew P. Morris1, Benjamin F. Voight2, Benjamin F. Voight3, Tanya M. Teslovich4 +229 more•Institutions (53)
TL;DR: This article conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent, and identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association.
Abstract: To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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University of California, Berkeley1, Lawrence Berkeley National Laboratory2, Australian Astronomical Observatory3, Pontifical Catholic University of Chile4, Harvard University5, Hamilton College6, University of Utah7, University of Tokyo8, Michigan State University9, Space Telescope Science Institute10, California Institute of Technology11, University of Colorado Boulder12, University of California, Santa Cruz13, University of Waterloo14, University of Chicago15, University of Florida16, Stockholm University17, University of Minnesota18, National Institutes of Natural Sciences, Japan19, Leiden University20, Northwestern University21, University of Bonn22, University of California, Davis23, University of Washington24, Kyoto University25, Pennsylvania State University26, European Southern Observatory27, Lawrence Livermore National Laboratory28, University of Lisbon29, Texas A&M University30, University of Toronto31
TL;DR: In this article, Advanced Camera for Surveys, NICMOS and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey was presented.
Abstract: We present Advanced Camera for Surveys, NICMOS, and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on board HST. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Union.
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TL;DR: New understandings of the diverse and dynamic effects on adolescent health include insights into the effects of puberty and brain development, together with social media, which provide important opportunities to improve health, both in adolescence and later in life.
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Bankstown Lidcombe Hospital1, Garvan Institute of Medical Research2, University of New South Wales3, University of Queensland4, Baylor College of Medicine5, Ontario Institute for Cancer Research6, University of Newcastle7, University of Sydney8, Royal North Shore Hospital9, Life Technologies10, St. Vincent's Health System11, Royal Prince Alfred Hospital12, Fremantle Hospital13, Royal Adelaide Hospital14, University of Western Australia15, University of California, Los Angeles16, University Health Network17, Mayo Clinic18, University of Toronto19, Johns Hopkins University20, University of Verona21, University of California, San Francisco22, Houston Methodist Hospital23, Cancer Research UK24, Wellcome Trust Sanger Institute25, University of Minnesota26, Netherlands Cancer Institute27
TL;DR: It is found that frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, are also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement ofAxon guidance genes in pancreatic carcinogenesis.
Abstract: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
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Johns Hopkins University1, Scripps Mercy Hospital2, Kingsbrook Jewish Medical Center3, Brigham Young University4, University of Minnesota5, Columbia University6, Boston Children's Hospital7, American Physical Therapy Association8, Marianjoy Rehabilitation Hospital and Clinics9, University of Melbourne10, University of Technology, Sydney11, National Institutes of Health12, Houston Methodist Hospital13, University of Chicago14, Northwestern University15, American Academy of Hospice and Palliative Medicine16, University of Cincinnati17, Society of Critical Care Medicine18
TL;DR: Improving care for intensive care survivors and their families requires collaboration between practitioners and researchers in both the inpatient and outpatient settings, and three major themes emerged from the conference.
Abstract: Background:Millions of patients are discharged from intensive care units annually. These intensive care survivors and their families frequently report a wide range of impairments in their health status which may last for months and years after hospital discharge.Objectives:To report on a 2-day Socie
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TL;DR: Improving adolescent health worldwide requires improving young people's daily life with families and peers and in schools, addressing risk and protective factors in the social environment at a population level, and focusing on factors that are protective across various health outcomes.
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American Cancer Society1, National Institutes of Health2, Emory University3, Memorial Sloan Kettering Cancer Center4, University of Minnesota5, University of Massachusetts Medical School6, University of Arizona7, University of New Mexico8, Harvard University9, Cornell University10, University of California, San Francisco11, McGill University12, University of Virginia13, American Society for Clinical Pathology14, Duke University15
TL;DR: An update to the ACS guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented, addressing age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing.
Abstract: An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.
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University of Minnesota1, Harvard University2, Veterans Health Administration3, Agency for Healthcare Research and Quality4, University of Pittsburgh5, University of Michigan6, United States Department of Veterans Affairs7, University of Texas at Dallas8, Washington University in St. Louis9, University of Oklahoma10, Baylor College of Medicine11
TL;DR: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up.
Abstract: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radi cal prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P = 0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P = 0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P = 0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P = 0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA test ing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials .gov number, NCT00007644.)
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University of Michigan1, Boston University2, National Research Council3, Johns Hopkins University4, University of Washington5, University of Pennsylvania6, Brown University7, University of Hasselt8, University of Minnesota9, Torcuato di Tella University10, Rutgers University11, Johnson & Johnson12, University of California, Irvine13
TL;DR: Methods for preventing missing data and, failing that, dealing with data that are missing in clinical trials are reviewed.
Abstract: Missing data in clinical trials can have a major effect on the validity of the inferences that can be drawn from the trial. This article reviews methods for preventing missing data and, failing that, dealing with data that are missing.
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TL;DR: A comprehensive meta-analysis is used to examine the relative yield performance of organic and conventional farming systems globally, and shows that, overall, organic yields are typically lower than conventional yields.
Abstract: Numerous reports have emphasized the need for major changes in the global food system: agriculture must meet the twin challenge of feeding a growing population, with rising demand for meat and high-calorie diets, while simultaneously minimizing its global environmental impacts. Organic farming—a system aimed at producing food with minimal harm to ecosystems, animals or humans—is often proposed as a solution. However, critics argue that organic agriculture may have lower yields and would therefore need more land to produce the same amount of food as conventional farms, resulting in more widespread deforestation and biodiversity loss, and thus undermining the environmental benefits of organic practices. Here we use a comprehensive meta-analysis to examine the relative yield performance of organic and conventional farming systems globally. Our analysis of available data shows that, overall, organic yields are typically lower than conventional yields. But these yield differences are highly contextual, depending on system and site characteristics, and range from 5% lower organic yields (rain-fed legumes and perennials on weak-acidic to weak-alkaline soils), 13% lower yields (when best organic practices are used), to 34% lower yields (when the conventional and organic systems are most comparable). Under certain conditions—that is, with good management practices, particular crop types and growing conditions—organic systems can thus nearly match conventional yields, whereas under others it at present cannot. To establish organic agriculture as an important tool in sustainable food production, the factors limiting organic yields need to be more fully understood, alongside assessments of the many social, environmental and economic benefits of organic farming systems.
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TL;DR: The existing dietary guidance on intake of fruits and vegetables is described, and attempts to characterizeruits and vegetables into groups based on similar chemical structures and functions are reviewed.
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TL;DR: In this article, the authors identify attributes of social media marketing (SMM) activities and examine the relationships among those perceived activities, value equity, relationship equity, brand equity, customer equity, and purchase intention through a structural equation model.
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University of Alabama at Birmingham1, University of California, Los Angeles2, University of California, San Diego3, Albany Medical College4, University of Pittsburgh5, University of Nebraska Omaha6, Oregon Health & Science University7, University of Texas MD Anderson Cancer Center8, University of Toronto9, University of Paris10, University of Michigan11, Mayo Clinic12, University of Minnesota13
TL;DR: The 2012 ACR RA recommendations were developed by two expert panels: a non-voting working group and Core Expert Panel of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis.
Abstract: The American College of Rheumatology (ACR) most recently published recommendations for use of disease modifying anti-rheumatic drugs (DMARDs) and biologics in the treatment of rheumatoid arthritis (RA) in 2008 (1). These recommendations covered indications for use, monitoring of side-effects, assessment of the clinical response to DMARDs and biologics, screening for tuberculosis (TB), and assessment of the roles of cost and patient preference in decision-making for biologic agents (1). Recognizing the rapidly evolving knowledge in RA management and the accumulation of new evidence regarding the safety and efficacy of existing and newer therapies, the ACR commissioned an update of the 2008 recommendations in select topic areas.
The 2012 revision updates the 2008 ACR recommendations in the following areas: (1) indications for DMARDs and biologics; (2) switching between DMARD and biologic therapies; (3) use of biologics in high-risk patients (those with hepatitis, congestive heart failure, and malignancy); (4) screening for TB in patients starting or currently receiving biologics; and (5) vaccination in patients starting or currently receiving DMARDs or biologics (Table 1).
Table 1
Overview Comparison of Topics and Medications Included in the 2008 and 2012 ACR RA Recommendations
METHODS
We utilized the same methodology as described in detail in the 2008 guidelines (1) to maintain consistency and to allow cumulative evidence to inform this 2012 recommendation update. These recommendations were developed by two expert panels: (1) a non-voting working group and Core Expert Panel (CEP) of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis and creation of “clinical scenarios”; and (2) a Task Force Panel (TFP) of 11 internationally-recognized expert clinicians, patient representatives and methodologists with expertise in RA treatment, evidence-based medicine and patient preferences who were tasked with rating the scenarios created using an ordinal scale specified in the Research and Development/University of California at Los Angeles (RAND/UCLA) Appropriateness method (2–4). This method solicited formal input from a multi-disciplinary TFP panel to make recommendations informed by the evidence. The methods used to develop the updated ACR recommendations are described briefly below.
Systematic Literature Review – Sources, Databases and Domains
Literature searches for both DMARDs and biologics relied predominantly on PubMed searches) with medical subject headings (MeSH) and relevant keywords similar to those used for the 2008 ACR RA recommendations (see Appendices 1 and 2). We included randomized clinical trials (RCTs), controlled clinical trials (CCTs), quasi-experimental designs, cohort studies (prospective or retrospective), and case-control studies, with no restrictions on sample size. More details about inclusion criteria are listed below and in Appendix 3.
The 2008 recommendations were based on a literature search that ended on February 14, 2007. The literature search end date for the 2012 Update was February 26, 2010 for the efficacy and safety studies and September 22, 2010 for additional qualitative reviews related to TB screening, immunization and hepatitis (similar to the 2008 methodology). Studies published subsequent to that date were not included.
For biologics, we also reviewed the Cochrane systematic reviews and overviews (published and in press) in the Cochrane Database of Systematic Reviews to identify additional studies (5–8) and further supplemented by hand-checking the bibliographies of all included articles. Finally, the CEP and TFP confirmed that relevant literature was included for evidence synthesis. Unless they were identified by the literature search and met the article inclusion criteria (see Appendix 3), we did not review any unpublished data from product manufacturers, investigators, or the Food and Drug Administration (FDA) Adverse Event Reporting System.
We searched the literature for the eight DMARDs and nine biologics most commonly used for the treatment of RA. Literature was searched for eight DMARDS including azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, minocycline, organic gold compounds and sulfasalazine. As in 2008, azathioprine, cyclosporine and gold were not included in the recommendations based on infrequent use and lack of new data (Table 1). Literature was searched for nine biologics including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab; anakinra was not included in the recommendations due to infrequent use and lack of new data. Details of the bibliographic search strategy are listed in Appendix 1.
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Clark University1, United States Department of Energy2, University of Minnesota3, Aix-Marseille University4, Spanish National Research Council5, Oregon State University6, University of Cincinnati Academic Health Center7, Utrecht University8, University of Zaragoza9, Duke University10, United States Department of Agriculture11, University of Warsaw12, University of Tokyo13, Nancy-Université14, University of Göttingen15, Pontifical Catholic University of Chile16, University of Helsinki17, Concordia University Wisconsin18, Vanderbilt University19, University of Wisconsin-Madison20, Swedish University of Agricultural Sciences21, Universidad Pública de Navarra22, Swansea University23
TL;DR: Comparative analyses of 31 fungal genomes suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species.
Abstract: Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non-lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period.
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TL;DR: A maladaptive personality trait model and corresponding instrument are developed as a step on the path toward helping users of DSM-5 assess traits that may or may not constitute a formal personality disorder.
Abstract: Background DSM-IV-TR suggests that clinicians should assess clinically relevant personality traits that do not necessarily constitute a formal personality disorder (PD), and should note these traits on Axis II, but DSM-IV-TR does not provide a trait model to guide the clinician. Our goal was to provide a provisional trait model and a preliminary corresponding assessment instrument, in our roles as members of the DSM-5 Personality and Personality Disorders Workgroup and workgroup advisors. Method An initial list of specific traits and domains (broader groups of traits) was derived from DSM-5 literature reviews and workgroup deliberations, with a focus on capturing maladaptive personality characteristics deemed clinically salient, including those related to the criteria for DSM-IV-TR PDs. The model and instrument were then developed iteratively using data from community samples of treatment-seeking participants. The analytic approach relied on tools of modern psychometrics (e.g. item response theory models). Results A total of 25 reliably measured core elements of personality description emerged that, together, delineate five broad domains of maladaptive personality variation: negative affect, detachment, antagonism, disinhibition, and psychoticism. Conclusions We developed a maladaptive personality trait model and corresponding instrument as a step on the path toward helping users of DSM-5 assess traits that may or may not constitute a formal PD. The inventory we developed is reprinted in its entirety in the Supplementary online material, with the goal of encouraging additional refinement and development by other investigators prior to the finalization of DSM-5. Continuing discussion should focus on various options for integrating personality traits into DSM-5.
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TL;DR: This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody‐mediated or mixed rejection and also underscores the major role of nonadherence.
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Wageningen University and Research Centre1, University of Edinburgh2, Iowa State University3, University College London4, Agro ParisTech5, Konkuk University6, Institut national de la recherche agronomique7, Aarhus University8, Aberystwyth University9, Seoul National University10, Norwich Research Park11, Wellcome Trust Sanger Institute12, Parco Tecnologico Padano13, University of Copenhagen14, University of Illinois at Urbana–Champaign15, University of Illinois at Chicago16, Agricultural Research Service17, Kansas State University18, Uppsala University19, European Bioinformatics Institute20, United States Department of Agriculture21, Washington University in St. Louis22, University of Kent23, Science for Life Laboratory24, Gyeongsang National University25, Genetic Information Research Institute26, Durham University27, University of California, Davis28, Pennsylvania State University29, University of Minnesota30, Jeju National University31, François Rabelais University32, University of California, Berkeley33, Glasgow Caledonian University34, Leipzig University35, Huazhong Agricultural University36
TL;DR: The assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago.
Abstract: For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.