Showing papers by "University of Minnesota published in 2015"

Second-generation PLINK: rising to the challenge of larger and richer datasets

Abstract: Background: PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for faster and scalable implementations of key functions, such as logistic regression, linkage disequilibrium estimation, and genomic distance evaluation. In addition, GWAS and population-genetic data now frequently contain genotype likelihoods, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1’s primary data format. Findings: To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O √ n -time/constant-space Hardy-Weinberg equilibrium and Fisher’s exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. We have also developed an extension to the data format which adds low-overhead support for genotype likelihoods, phase, multiallelic variants, and reference vs. alternate alleles, which is the basis of our planned second release (PLINK 2.0). Conclusions: The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.

The MovieLens Datasets: History and Context

Abstract: The MovieLens datasets are widely used in education, research, and industry. They are downloaded hundreds of thousands of times each year, reflecting their use in popular press programming books, traditional and online courses, and software. These datasets are a product of member activity in the MovieLens movie recommendation system, an active research platform that has hosted many experiments since its launch in 1997. This article documents the history of MovieLens and the MovieLens datasets. We include a discussion of lessons learned from running a long-standing, live research platform from the perspective of a research organization. We document best practices and limitations of using the MovieLens datasets in new research.

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection : a case control study

Abstract: Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

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.

Combined Measurement of the Higgs Boson Mass in pp Collisions at √s=7 and 8 TeV with the ATLAS and CMS Experiments

Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

Crystallization by particle attachment in synthetic, biogenic, and geologic environments

Abstract: Field and laboratory observations show that crystals commonly form by the addition and attachment of particles that range from multi-ion complexes to fully formed nanoparticles. The particles involved in these nonclassical pathways to crystallization are diverse, in contrast to classical models that consider only the addition of monomeric chemical species. We review progress toward understanding crystal growth by particle-attachment processes and show that multiple pathways result from the interplay of free-energy landscapes and reaction dynamics. Much remains unknown about the fundamental aspects, particularly the relationships between solution structure, interfacial forces, and particle motion. Developing a predictive description that connects molecular details to ensemble behavior will require revisiting long-standing interpretations of crystal formation in synthetic systems, biominerals, and patterns of mineralization in natural environments.

Characterization of the LIGO detectors during their sixth science run

Abstract: In 2009–2010, the Laser Interferometer Gravitational-Wave Observatory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves (GWs) of astrophysical origin. The sensitivity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the GW readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.

Joint Analysis of BICEP2/Keck Array and Planck Data

Abstract: We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg2 patch of sky centered on RA 0h, Dec. −57.5deg. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 μK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B-modes at high significance. We fit the single- and cross-frequency power spectra at frequencies above 150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parameterized by the tensor-to-scalar ratio r). We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r0.05<0.12 at 95% confidence. Marginalizing over dust and r, lensing B-modes are detected at 7.0σ significance.

Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society

Abstract: Importance Breast cancer is a leading cause of premature mortality among US women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. Objective To update the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. Process The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. Evidence Synthesis Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening for women 70 years and older who are in good health. Estimates of the cumulative lifetime risk of false-positive examination results are greater if screening begins at younger ages because of the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs biennially. Evidence does not support routine clinical breast examination as a screening method for women at average risk. Recommendations The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation). Conclusions and Relevance These updated ACS guidelines provide evidence-based recommendations for breast cancer screening for women at average risk of breast cancer. These recommendations should be considered by physicians and women in discussions about breast cancer screening.

Bariatric Surgery Worldwide 2013.

Abstract: The first global survey of bariatric/metabolic surgery based on data from the nations or national groupings of the International Federation for the Surgery of Obesity and Metabolic Diseases (IFSO) was published in 1998, followed by reports in 2003, 2009, 2011, and 2012. In this survey, we report a global overview of worldwide bariatric surgery in 2013. A questionnaire evaluating the number and the type of bariatric procedure performed in 2013 was emailed to all members of bariatric societies belonging to IFSO. Trend analyses from 2003 to 2013 were also performed. There were 49/54 (90.7 %) responders; 37 of the 49 with national registries. The total number of bariatric procedures performed worldwide in 2013 was 468,609, 95.7 % carried out laparoscopically. The highest number (n = 154,276) was from the USA/Canada region. The most commonly performed procedure in the world was Roux-en-Y gastric bypass (RYGB), 45 %; followed by sleeve gastrectomy (SG), 37 %; and adjustable gastric banding (AGB), 10 %. Most significant were the rise in prevalence of SG from 0 to 37 % of the world total from 2003 to 2013, and the fall in AGB of 68 % from its peak in 2008 to 2013. SG is currently the most frequently performed procedure in the USA/Canada and in the Asia/Pacific regions, and second to RYGB in the Europe and Latin/South America regions. The accuracy of the IFSO-based world survey of procedures would be enhanced if each nation or national group would create a national registry.

Evidence-Based Practices for Children, Youth, and Young Adults with Autism Spectrum Disorder: A Comprehensive Review.

Abstract: The purpose of this study was to identify evidenced-based, focused intervention practices for children and youth with autism spectrum disorder. This study was an extension and elaboration of a previous evidence-based practice review reported by Odom et al. (Prev Sch Fail 54:275–282, 2010b, doi: 10.1080/10459881003785506 ). In the current study, a computer search initially yielded 29,105 articles, and the subsequent screening and evaluation process found 456 studies to meet inclusion and methodological criteria. From this set of research studies, the authors found 27 focused intervention practices that met the criteria for evidence-based practice (EBP). Six new EBPs were identified in this review, and one EBP from the previous review was removed. The authors discuss implications for current practices and future research.

Climate variation explains a third of global crop yield variability

Abstract: Many studies have examined the role of mean climate change in agriculture, but an understanding of the influence of inter-annual climate variations on crop yields in different regions remains elusive. We use detailed crop statistics time series for ~13,500 political units to examine how recent climate variability led to variations in maize, rice, wheat and soybean crop yields worldwide. While some areas show no significant influence of climate variability, in substantial areas of the global breadbaskets, >60% of the yield variability can be explained by climate variability. Globally, climate variability accounts for roughly a third (~32-39%) of the observed yield variability. Our study uniquely illustrates spatial patterns in the relationship between climate variability and crop yield variability, highlighting where variations in temperature, precipitation or their interaction explain yield variability. We discuss key drivers for the observed variations to target further research and policy interventions geared towards buffering future crop production from climate variability.

Multi-terminal transport measurements of MoS2 using a van der Waals heterostructure device platform.

Abstract: High charge-carrier mobility that enables the observation of quantum oscillation is reported in mono- and few-layer MoS2 encapsulated and contacted by other two-dimensional materials.

An introduction to implementation science for the non-specialist

Abstract: The movement of evidence-based practices (EBPs) into routine clinical usage is not spontaneous, but requires focused efforts. The field of implementation science has developed to facilitate the spread of EBPs, including both psychosocial and medical interventions for mental and physical health concerns. The authors aim to introduce implementation science principles to non-specialist investigators, administrators, and policymakers seeking to become familiar with this emerging field. This introduction is based on published literature and the authors’ experience as researchers in the field, as well as extensive service as implementation science grant reviewers. Implementation science is “the scientific study of methods to promote the systematic uptake of research findings and other EBPs into routine practice, and, hence, to improve the quality and effectiveness of health services.” Implementation science is distinct from, but shares characteristics with, both quality improvement and dissemination methods. Implementation studies can be either assess naturalistic variability or measure change in response to planned intervention. Implementation studies typically employ mixed quantitative-qualitative designs, identifying factors that impact uptake across multiple levels, including patient, provider, clinic, facility, organization, and often the broader community and policy environment. Accordingly, implementation science requires a solid grounding in theory and the involvement of trans-disciplinary research teams. The business case for implementation science is clear: As healthcare systems work under increasingly dynamic and resource-constrained conditions, evidence-based strategies are essential in order to ensure that research investments maximize healthcare value and improve public health. Implementation science plays a critical role in supporting these efforts.

Body Mass Index: Obesity, BMI, and Health: A Critical Review

Abstract: The body mass index (BMI) is the metric currently in use for defining anthropometric height/weight characteristics in adults and for classifying (categorizing) them into groups. The common interpretation is that it represents an index of an individual's fatness. It also is widely used as a risk factor for the development of or the prevalence of several health issues. In addition, it is widely used in determining public health policies.The BMI has been useful in population-based studies by virtue of its wide acceptance in defining specific categories of body mass as a health issue. However, it is increasingly clear that BMI is a rather poor indicator of percent of body fat. Importantly, the BMI also does not capture information on the mass of fat in different body sites. The latter is related not only to untoward health issues but to social issues as well. Lastly, current evidence indicates there is a wide range of BMIs over which mortality risk is modest, and this is age related. All of these issues are discussed in this brief review.

Cooperative insertion of CO2 in diamine-appended metal-organic frameworks

Abstract: The process of carbon capture and sequestration has been proposed as a method of mitigating the build-up of greenhouse gases in the atmosphere. If implemented, the cost of electricity generated by a fossil fuel-burning power plant would rise substantially, owing to the expense of removing CO2 from the effluent stream. There is therefore an urgent need for more efficient gas separation technologies, such as those potentially offered by advanced solid adsorbents. Here we show that diamine-appended metal-organic frameworks can behave as 'phase-change' adsorbents, with unusual step-shaped CO2 adsorption isotherms that shift markedly with temperature. Results from spectroscopic, diffraction and computational studies show that the origin of the sharp adsorption step is an unprecedented cooperative process in which, above a metal-dependent threshold pressure, CO2 molecules insert into metal-amine bonds, inducing a reorganization of the amines into well-ordered chains of ammonium carbamate. As a consequence, large CO2 separation capacities can be achieved with small temperature swings, and regeneration energies appreciably lower than achievable with state-of-the-art aqueous amine solutions become feasible. The results provide a mechanistic framework for designing highly efficient adsorbents for removing CO2 from various gas mixtures, and yield insights into the conservation of Mg(2+) within the ribulose-1,5-bisphosphate carboxylase/oxygenase family of enzymes.

Biodiversity increases the resistance of ecosystem productivity to climate extremes

Abstract: It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide1. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities2. However, subsequent experimental tests produced mixed results3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16–32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability14, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe

Abstract: Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.

Redefining fine roots improves understanding of below-ground contributions to terrestrial biosphere processes

Abstract: Fine roots acquire essential soil resources and mediate biogeochemical cycling in terrestrial ecosystems. Estimates of carbon and nutrient allocation to build and maintain these structures remain uncertain because of the challenges of consistently measuring and interpreting fine-root systems. Traditionally, fine roots have been defined as all roots 2mm in diameter, yet it is now recognized that this approach fails to capture the diversity of form and function observed among fine-root orders. Here, we demonstrate how order-based and functional classification frameworks improve our understanding of dynamic root processes in ecosystems dominated by perennial plants. In these frameworks, fine roots are either separated into individual root orders or functionally defined into a shorter-lived absorptive pool and a longer-lived transport fine-root pool. Using these frameworks, we estimate that fine-root production and turnover represent 22% of terrestrial net primary production globally - a c. 30% reduction from previous estimates assuming a single fine-root pool. Future work developing tools to rapidly differentiate functional fine-root classes, explicit incorporation of mycorrhizal fungi into fine-root studies, and wider adoption of a two-pool approach to model fine roots provide opportunities to better understand below-ground processes in the terrestrial biosphere.

Rapid and highly variable warming of lake surface waters around the globe

Abstract: In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.

Biomarkers of Nutrition for Development (BOND)-Iron Review.

Abstract: The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

A positive-negative mode of population covariation links brain connectivity, demographics and behavior

Abstract: We investigated the relationship between individual subjects' functional connectomes and 280 behavioral and demographic measures in a single holistic multivariate analysis relating imaging to non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.

Waveguide-integrated black phosphorus photodetector with high responsivity and low dark current

Abstract: A gated multilayer black phosphorus photodetector integrated on a silicon photonic waveguide operating in the telecom band is demonstrated with intrinsic responsivity up to 135 mA W−1 and 657 mA W−1 in 11.5-nm- and 100-nm-thick devices, respectively.

Impact of weight bias and stigma on quality of care and outcomes for patients with obesity

Abstract: The objective of this study was to critically review the empirical evidence from all relevant disciplines regarding obesity stigma in order to (i) determine the implications of obesity stigma for healthcare providers and their patients with obesity and (ii) identify strategies to improve care for patients with obesity. We conducted a search of Medline and PsychInfo for all peer-reviewed papers presenting original empirical data relevant to stigma, bias, discrimination, prejudice and medical care. We then performed a narrative review of the existing empirical evidence regarding the impact of obesity stigma and weight bias for healthcare quality and outcomes. Many healthcare providers hold strong negative attitudes and stereotypes about people with obesity. There is considerable evidence that such attitudes influence person-perceptions, judgment, interpersonal behaviour and decision-making. These attitudes may impact the care they provide. Experiences of or expectations for poor treatment may cause stress and avoidance of care, mistrust of doctors and poor adherence among patients with obesity. Stigma can reduce the quality of care for patients with obesity despite the best intentions of healthcare providers to provide high-quality care. There are several potential intervention strategies that may reduce the impact of obesity stigma on quality of care.

Destruction of chemical warfare agents using metal–organic frameworks

Abstract: Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic Zr(IV) ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial

Abstract: Background—Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). Methods and Results—To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial i...

Addressing Global Mortality from Ambient PM2.5

Abstract: Ambient fine particulate matter (PM2.5) has a large and well-documented global burden of disease. Our analysis uses high-resolution (10 km, global-coverage) concentration data and cause-specific integrated exposure-response (IER) functions developed for the Global Burden of Disease 2010 to assess how regional and global improvements in ambient air quality could reduce attributable mortality from PM2.5. Overall, an aggressive global program of PM2.5 mitigation in line with WHO interim guidelines could avoid 750 000 (23%) of the 3.2 million deaths per year currently (ca. 2010) attributable to ambient PM2.5. Modest improvements in PM2.5 in relatively clean regions (North America, Europe) would result in surprisingly large avoided mortality, owing to demographic factors and the nonlinear concentration-response relationship that describes the risk of particulate matter in relation to several important causes of death. In contrast, major improvements in air quality would be required to substantially reduce mort...