Myocardial changes in incident haemodialysis patients over 6-months:an observational cardiac magnetic resonance imaging study

Patients commencing on haemodialysis (HD) have an increased risk of cardiovascular events in the first year after starting HD compared to those patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal myocardial strain predict mortality. There may be changes in the myocardium of incident HD patients over a 6-month period of HD which may explain changes in cardiovascular risk. We used CMR to consider changes in LV mass, myocardial strain and T1 mapping. We examined changes in pre-dialysis highly sensitive troponin T. 33 patients undergoing HD for <12 months were recruited. Participants underwent CMR at baseline and after 6-months of standard care. 6-months of HD was associated with reduction in LV mass index (Baseline: 78.8 g/m2 follow up: 69.9 g/m2, p = <0.001). LV global longitudinal strain also improved (Baseline: −17.9%, follow up: −21.6%, p = <0.001). Change in T1 time was not significant (Baseline septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In incident HD patients, 6-months of HD was associated with improvements in LV mass, strain and troponin. These findings may reflect improvement in known cardiac tissue abnormalities found in patients over the first year of HD

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Exploring haemodynamics of haemodialysis using extrema points analysis model

Background: Haemodialysis is a form of renal replacement therapy used to treat patients with end stage renal failure. It is becoming more appreciated that haemodialysis patients exhibit higher rates of multiple end organ damage compared to the general population. There is also a strong emerging evidence that haemodialysis itself causes circulatory stress. We aimed at examining haemodynamic patterns during haemodialysis using a new model and test that model against a normal control. Methods: We hypothesised that blood pressures generated by each heart beat constantly vary between local peaks and troughs (local extrema), the frequency and amplitude of which is regulated to maintain optimal organ perfusion. We also hypothesised that such model could reveal multiple haemodynamic aberrations during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we compared various haemodynamic parameters using the above model between a haemodialysis patient during a dialysis session and an exercised normal control after comparison at rest. Results: Measurements yielded 29,751 data points for each haemodynamic parameter. Extrema points frequency of mean arterial blood pressure was higher in the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood pressure was significantly higher in haemodialysis compared to normal. In contrary, the frequency of extrema points for TPR was higher in the normal control compared to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly higher amplitudes. Conclusion: Haemodialysis patients potentially exhibit an aberrant haemodynamic behaviour characterised by higher extrema frequencies of mean arterial blood pressure and lower extrema frequencies of total peripheral resistance. This, in theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

A programme to spread eGFR graph surveillance for the early identification, support and treatment of people with progressive chronic kidney disease (ASSIST-CKD): protocol for the stepped wedge implementation and evaluation of an intervention to reduce late presentation for renal replacement therapy

Background Patients who start renal replacement therapy (RRT) for End-Stage Kidney Disease (ESKD) without having had timely access to specialist renal services have poor outcomes. At one NHS Trust in England, a community-wide CKD management system has led to a decline in the incident rate of RRT and the lowest percentage of patients presenting within 90 days of starting RRT in the UK. We describe the protocol for a quality improvement project to scale up and evaluate this innovation. Methods The intervention is based upon an off-line database that integrates laboratory results from blood samples taken in all settings stored under different identifying labels relating to the same patient. Graphs of estimated glomerular filtration rate (eGFR) over time are generated for patients 65 years with an incoming eGFR <40 ml/min/1.73 m2. Graphs where kidney function is deteriorating are flagged by a laboratory scientist and details sent to the primary care doctor (GP) with a prompt that further action may be needed. We will evaluate the impact of implementing this intervention across a large population served by a number of UK renal centres using a mixed methods approach. We are following a stepped-wedge design. The order of implementation among participating centres will be randomly allocated. Implementation will proceed with unidirectional steps from control group to intervention group until all centres are generating graphs of eGFR over time. The primary outcome for the quantitative evaluation is the proportion of patients referred to specialist renal services within 90 days of commencing RRT, using data collected routinely by the UK Renal Registry. The qualitative evaluation will investigate facilitators and barriers to adoption and spread of the intervention. It will include: semi-structured interviews with laboratory staff, renal centre staff and service commissioners; an online survey of GPs receiving the intervention; and focus groups of primary care staff. Discussion Late presentation to nephrology for patients with ESKD is a source of potentially avoidable harm. This protocol describes a robust quantitative and qualitative evaluation of a quality improvement intervention to reduce late presentation and improve the outcomes for patients with ESKD

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Optimizing the procedure of grain nutrient predictions in barley via hyperspectral imaging

Hyperspectral imaging enables researchers and plant breeders to analyze various traits of interest like nutritional value in high throughput. In order to achieve this, the optimal design of a reliable calibration model, linking the measured spectra with the investigated traits, is necessary. In the present study we investigated the impact of different regression models, calibration set sizes and calibration set compositions on prediction performance. For this purpose, we analyzed concentrations of six globally relevant grain nutrients of the wild barley population HEB-YIELD as case study. The data comprised 1,593 plots, grown in 2015 and 2016 at the locations Dundee and Halle, which have been entirely analyzed through traditional laboratory methods and hyperspectral imaging. The results indicated that a linear regression model based on partial least squares outperformed neural networks in this particular data modelling task. There existed a positive relationship between the number of samples in a calibration model and prediction performance, with a local optimum at a calibration set size of ~40% of the total data. The inclusion of samples from several years and locations could clearly improve the predictions of the investigated nutrient traits at small calibration set sizes. It should be stated that the expansion of calibration models with additional samples is only useful as long as they are able to increase trait variability. Models obtained in a certain environment were only to a limited extent transferable to other environments. They should therefore be successively upgraded with new calibration data to enable a reliable prediction of the desired traits. The presented results will assist the design and conceptualization of future hyperspectral imaging projects in order to achieve reliable predictions. It will in general help to establish practical applications of hyperspectral imaging systems, for instance in plant breeding concepts

Cross sections and transverse single-spin asymmetries in forward neutral-pion production from proton collisions at root s=200 GeV

Measurements of the production of forward high-energy pi(0) mesons from transversely polarized proton collisions at root200 GeV are reported. The cross section is generally consistent with next-to-leading order perturbative QCD calculations. The analyzing power is small at x(F) below about 0.3, and becomes positive and large at higher x(F), similar to the trend in data at roots less than or equal to20 GeV. The analyzing power is in qualitative agreement with perturbative QCD model expectations. This is the first significant spin result seen for particles produced with p(T)>1 GeV/c at a polarized proton collider