Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Purpose. To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients. Methods. Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models. Results. The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables. Conclusion. Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification

Solar wind dynamic pressure and electric field as the main factors controlling Saturn's aurorae

The interaction of the solar wind with Earth's magnetosphere gives rise to the bright polar aurorae and to geomagnetic storms(1), but the relation between the solar wind and the dynamics of the outer planets' magnetospheres is poorly understood. Jupiter's magnetospheric dynamics and aurorae are dominated by processes internal to the jovian system(2), whereas Saturn's magnetosphere has generally been considered to have both internal and solar-wind-driven processes. This hypothesis, however, is tentative because of limited simultaneous solar wind and magnetospheric measurements. Here we report solar wind measurements, immediately upstream of Saturn, over a one-month period. When combined with simultaneous ultraviolet imaging(3) we find that, unlike Jupiter, Saturn's aurorae respond strongly to solar wind conditions. But in contrast to Earth, the main controlling factor appears to be solar wind dynamic pressure and electric field, with the orientation of the interplanetary magnetic field playing a much more limited role. Saturn's magnetosphere is, therefore, strongly driven by the solar wind, but the solar wind conditions that drive it differ from those that drive the Earth's magnetosphere.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62975/1/nature03333.pd

Ultraviolet emissions from the magnetic footprints of Io, Ganymede and Europa on Jupiter

Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates(1-3). The specific physical mechanisms responsible for generating those emissions are not well understood, but in general the spot seems to arise because of an electromagnetic interaction between Jupiter's magnetic field and the plasma surrounding Io, driving currents of around 1 million amperes down through Jupiter's ionosphere(4-6). The other galilean satellites may also leave footprints, and the presence or absence of such footprints should illuminate the underlying physical mechanism by revealing the strengths of the currents linking the satellites to Jupiter. Here we report persistent, faint, far-ultraviolet emission from the jovian footprints of Ganymede and Europa. We also show that Io's magnetic footprint extends well beyond the immediate vicinity of Io's flux-tube interaction with Jupiter, and much farther than predicted theoretically(4-6); the emission persists for several hours downstream. We infer from these data that Ganymede and Europa have persistent interactions with Jupiter's magnetic field despite their thin atmospheres.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62861/1/415997a.pd

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Lipids and carotid plaque in the Northern Manhattan Study (NOMAS)

<p>Abstract</p> <p>Background</p> <p>Lipids, particularly low-density (LDL) and high-density (HDL) lipoproteins, are associated with increased risk of stroke and cardiovascular disease, probably due to atherosclerosis. The objective of this cross-sectional analysis was to investigate the relation between blood lipids and carotid plaque.</p> <p>Methods</p> <p>As part of a prospective population-based study to determine the incidence and risk factors of stroke in a multiethnic population, we evaluated 1804 participants with lipid measurements and B-mode ultrasound of carotid arteries (mean age 69 +/- 10 years; 40% men; 51% Hispanic, 26% black, 23% white). The association between lipid parameters and carotid plaque was analyzed by multiple logistic regression.</p> <p>Results</p> <p>Plaque was present in 61% of participants. Mean total cholesterol was 202 +/- 41 mg/dl. After controlling for other lipid parameters, demographics, and risk factors, the only cholesterol subfraction associated with carotid plaque was LDL (OR per standard deviation (SD) = 1.14, 95% CI 1.02-1.27). Neither HDL nor triglycerides independently predicted carotid plaque. Apolipoprotein B (ApoB) was also associated with risk of plaque (OR per SD = 1.29, 95% CI 1.03-1.60). Apolipoprotein A-I (apoA-1) was associated with a decrease in multiple plaques (OR per SD = 0.76, 95% CI 0.60-0.97), while lipoprotein a was associated with an increased risk of multiple plaques (OR per SD = 1.31, 95% CI 1.03-1.66). ApoB:ApoA-I had the strongest relation with carotid plaque (OR per SD = 1.35, 95% CI 1.08-1.69).</p> <p>Conclusions</p> <p>Among the common lipid parameters, LDL has the strongest relation with carotid plaque. Other lipid precursor proteins such as ApoB and ApoA-I may be stronger predictors of subclinical atherosclerosis, however, and better targets for treatment to reduce plaque formation and risk of cerebrovascular disease.</p

One More Piece in the VACV Ecological Puzzle: Could Peridomestic Rodents Be the Link between Wildlife and Bovine Vaccinia Outbreaks in Brazil?

BACKGROUND: Despite the fact that smallpox eradication was declared by the World Health Organization (WHO) in 1980, other poxviruses have emerged and re-emerged, with significant public health and economic impacts. Vaccinia virus (VACV), a poxvirus used during the WHO smallpox vaccination campaign, has been involved in zoonotic infections in Brazilian rural areas (Bovine Vaccinia outbreaks - BV), affecting dairy cattle and milkers. Little is known about VACV's natural hosts and its epidemiological and ecological characteristics. Although VACV was isolated and/or serologically detected in Brazilian wild animals, the link between wildlife and farms has not yet been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we describe for the first time, to our knowledge, the isolation of a VACV (Mariana virus - MARV) from a mouse during a BV outbreak. Genetic data, in association with biological assays, showed that this isolate was the same etiological agent causing exanthematic lesions observed in the cattle and human inhabitants of a particular BV-affected area. Phylogenetic analysis grouped MARV with other VACV isolated during BV outbreaks. CONCLUSION/SIGNIFICANCE: These data provide new biological and epidemiological information on VACV and lead to an interesting question: could peridomestic rodents be the link between wildlife and BV outbreaks

Temporal Expression of Chemokines Dictates the Hepatic Inflammatory Infiltrate in a Murine Model of Schistosomiasis

Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs) and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1), members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12) and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14) and markers of alternatively activated macrophages (e.g. Retnla) during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic zone of granulomas. Furthermore, striking up-regulation of neutrophil markers and the localisation of neutrophils and the neutrophil chemokine S100A8 to fibrotic areas suggest the involvement of neutrophils in S. japonicum-induced hepatic fibrosis. These results further our understanding of the immunopathogenic and, especially, chemokine signalling pathways that regulate the development of S. japonicum-induced granulomas and fibrosis and may provide correlative insight into the pathogenesis of other chronic inflammatory diseases of the liver where fibrosis is a common feature