A cluster randomized controlled trial of a modified vaccination clinical reminder for primary care providers

Objective: Adult vaccination rates in the United States fall short of national goals, and rates are particularly low for Black Americans. We tested a provider-focused vaccination uptake intervention: a modified electronic health record clinical reminder that bundled together three adult vaccination reminders, presented patient vaccination history, and included talking points for providers to address vaccine hesitancy. Method: Primary care teams at the Atlanta Veterans Affairs Medical Center, who saw 28,941 patients during this period, were randomly assigned to receive either the modified clinical reminder (N = 44 teams) or the status quo (N = 40 teams). Results: Uptake of influenza and other adult vaccinations was 1.6 percentage points higher in the intervention group, which was not statistically significant (CI = [-1.3, 4.4], p = 0.28). The intervention had similar effects on Black and White patients and did not reduce the disparity in vaccination rates between these groups. Conclusion: Provider-focused interventions are a promising way to address vaccine hesitancy, but they may need to be more intensive than a modified clinical reminder to have appreciable effects on vaccination uptake

Targeting Ovarian Cancer and Endothelium with an Allosteric PTP4A3 Phosphatase Inhibitor

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, selective, reversible, and noncompetitive PTP4A inhibitor, JMS-053, markedly enhanced microvascular barrier function after exposure of endothelial cells to vascular endothelial growth factor or lipopolysaccharide. JMS-053 also blocked the concomitant increase in RhoA activation and loss of Rac1. In human ovarian cancer cells, JMS-053 impeded migration, disrupted spheroid growth, and decreased RhoA activity. Importantly, JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer. These data demonstrate that PTP4A phosphatases can be targeted in both endothelial and ovarian cancer cells, and confirm that RhoA signaling cascades are regulated by the PTP4A family

Austenite Formation Kinetics During Rapid Heating in a Microalloyed Steel

The model parameters for the normalized 1054V1 material were compared to parameters previously generated for 1026 steel, and the transformation behavior was relatively consistent. Validation of the model predictions by heating into the austenite plus undissolved ferrite phase field and rapidly quenching resulted in reasonable predictions when compared to the measured volume fractions from optical metallography. The hot rolled 1054V1 material, which had a much coarser grain size and a non-equilibrium volume fraction of pearlite, had significantly different model parameters and the on heating transformation behavior of this material was less predictable with the established model. The differences in behavior is consistent with conventional wisdom that normalized micro-structure produce a more consistent response to processing, and it reinforces the need for additional work in this area

Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015

Background Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. Methods We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure–response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure–response functions spanning the global range of exposure. Findings Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000–422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. Interpretation Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction

Beyond the call of duty: Why customers contribute to firm-hosted commercial online communities

Firm-hosted commercial online communities, in which customers interact to solve each other's service problems, represent a fascinating context to study the motivations of collective action in the form of knowledge contribution to the community. We extend a model of social capital based on Wasko and Faraj (2005) to incorporate and contrast the direct impact of commitment to both the online community and the host firm, as well as reciprocity, on quality and quantity of knowledge contribution. In addition, we examine the moderating influence of three individual attributes that are particularly relevant to the firm-hosted community context: perceived informational value, sportsmanship, and online interaction propensity. We empirically test our framework using self-reported and objective data from 203 members of a firm-hosted technical support community. In addition to several interesting moderating effects, we find that a customer's online interaction propensity, commitment to the community, and the informational value s/he perceives in the community are the strongest drivers of knowledge contribution

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations