The depression in visual impairment trial (DEPVIT): trial design and protocol

<b>Background</b> The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p> <b>Methods/design</b> The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p> <b>Discussion</b> Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p&gt

Macroscopic invisibility cloaking of visible light

Invisibility cloaks, which used to be confined to the realm of fiction, have now been turned into a scientific reality thanks to the enabling theoretical tools of transformation optics and conformal mapping. Inspired by those theoretical works, the experimental realization of electromagnetic invisibility cloaks has been reported at various electromagnetic frequencies. All the invisibility cloaks demonstrated thus far, however, have relied on nano- or micro-fabricated artificial composite materials with spatially varying electromagnetic properties, which limit the size of the cloaked region to a few wavelengths. Here, we report the first realization of a macroscopic volumetric invisibility cloak constructed from natural birefringent crystals. The cloak operates at visible frequencies and is capable of hiding, for a specific light polarization, three-dimensional objects of the scale of centimetres and millimetres. Our work opens avenues for future applications with macroscopic cloaking devices

Mitral paravalvular abscess with left ventriculo-atrial fistula in a patient on dialysis

Background: Infective endocarditis in hemodialysis patients is challenging but is becoming more common recently. Case report: A 64-year-old man with end-stage renal disease on hemodialysis presented with infective endocarditis of mitral valve and coronary artery disease after commencing training for home hemodialysis. During a course of antibiotic treatment the patient developed left ventriculo-atrial fistula due to mitral paravalvular abscess. Abscess debridement followed by reconstruction of the mitral annulus with fresh autologous pericardial patch and mitral valve replacement using a mechanical prosthesis with concomitant coronary artery bypass grafting was performed successfully. Conclusion: Timely diagnosis, proper antibiotic treatment and early surgical intervention including aggressive debridement should improve the outcome of this high-risk disease. © 2009 Kitamura et al; licensee BioMed Central Ltd.Tadashi Kitamura, James Edwards, Suchi Khurana and Robert G Stukli

Virus–Host Interactions Between Nonsecretors and Human Norovirus

BACKGROUND & AIMS: Human norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by the FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set of fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) express a limited array of HBGAs. Thus, nonsecretors have less diverse norovirus strain infections, including resistance to the epidemiologically dominant GII.4 strains. Because future human norovirus vaccines will comprise GII.4 antigen and because secretor phenotype impacts GII.4 infection and immunity, nonsecretors may mimic young children immunologically in response to GII.4 vaccination, providing a needed model to study crossprotection in the context of limited pre-exposure. METHODS: By using specimens collected from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus, we evaluated the breadth of serologic immunity by surrogate neutralization assays, and cellular activation and cytokine production by flow cytometry. RESULTS: GII.2 infection resulted in broad antibody and cellular immunity activation that persisted for at least 30 days for T cells, monocytes, and dendritic cells, and for 180 days for blocking antibody. Multiple cellular lineages expressing interferon-g and tumor necrosis factor-a dominated the response. Both T-cell and B-cell responses were cross-reactive with other GII strains, but not GI strains. To promote entry mechanisms, inclusion of bile acids was essential for GII.2 binding to nonsecretor HBGAs. CONCLUSIONS: These data support development of withingenogroup, cross-reactive antibody and T-cell immunity, key outcomes that may provide the foundation for eliciting broad immune responses after GII.4 vaccination in individuals with limited GII.4 immunity, including young children

Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial

Background: Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. We assessed the long-term effects of canagliflozin on anaemia-related outcomes. Methods: In a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we included patients with type 2 diabetes and chronic kidney disease who were randomly assigned to treatment with canagliflozin or placebo at 690 sites in 34 countries. We assessed the effects of canagliflozin versus matched placebo on haemoglobin and haematocrit using linear mixed-effects models. The primary outcome of this post-hoc analysis was a composite outcome of investigator-reported anaemia or treatment for anaemia, which was assessed using Kaplan-Meier analysis and Cox regression models. All analyses were done by intention to treat. Findings: Between March 24, 2014, and May 5, 2017, 4401 participants were randomly assigned to receive canagliflozin (100 mg; n=2202) or placebo (n=2199). At baseline, mean haemoglobin concentration was 132·0 g/L (SD 17·7), 1599 (36%) of 4401 participants had anaemia (defined as haemoglobin <130 g/L in men or <120 g/L in women), and 33 (<1%) of 4401 participants used erythropoiesis-stimulating agents. During a median follow-up period of 2·6 years (IQR 2·1–3·1), mean haemoglobin concentration was 7·1 g/L (95% CI 6·4–7·8) higher and haematocrit was 2·4% (2·2–2·6) higher in the canagliflozin group than the placebo group. Overall, 573 of 4401 participants had either an investigator-reported anaemia event or initiation of treatment for anaemia: 358 (8%) of 4401 participants reported anaemia events, 343 (8%) initiated iron preparations, 141 (3%) initiated erythropoiesis-stimulating agents, and 114 (2%) received blood transfusion. The risk of the composite outcome of anaemia events or initiation of treatment for anaemia was lower in the canagliflozin group than the placebo group (hazard ratio 0·65, 95% CI 0·55–0·77; p<0·0001). Compared with the placebo group, participants in the canagliflozin group also had lower risks of anaemia events alone (0·58, 0·47–0·72; p<0·0001), initiation of iron preparations (0·64, 0·52–0·80; p<0·0001), and need for erythropoiesis-stimulating agents (0·65, 0·46–0·91; p=0·012). Interpretation: These data suggest that canagliflozin reduces the risk of anaemia-associated outcomes, including the need for erythropoiesis-stimulating agents, among patients with type 2 diabetes and chronic kidney disease

Careers of an elite cohort of U.S. basic life science postdoctoral fellows and the influence of their mentor's citation record

<p>Abstract</p> <p>Background</p> <p>There is general agreement that the number of U.S. science PhDs being trained far exceeds the number of future academic positions. One suggested approach to this problem is to significantly reduce the number of PhD positions. A counter argument is that students are aware of the limited academic positions but have chosen a PhD track because it opens other, non-academic, opportunities. The latter view requires that students have objective information about what careers options will be available for them.</p> <p>Methods</p> <p>The scientific careers of the 1992-94 cohort of NIH National Institute of General Medical Sciences (NIGMS) Kirchstein-NRSA F32 postdoctoral fellows (PD) was determined by following their publications (PubMed), grants (NIH and NSF), and faculty and industry positions through 2009. These basic life science PDs receive support through individual grant applications and represent the most successful class of NIH PDs as judged by academic careers and grants. The sex dependence of the career and grant success and the influence of the PD mentor's citation record were also determined</p> <p>Results</p> <p>Of the 439 1992-94 NIGMS F32 fellows, the careers of 417 could be determined. Although females had significantly higher rates of dropping out of science (22% females, 9% males) there was no significant difference in the fraction of females that ended up as associate or full professors at research universities (22.8% females, 29.1% for males). More males then females ended up in industry (34% males, 22% females). Although there was no significant correlation between male grant success and their mentor's publication record (h index, citations, publications), there was a significant correlation for females. Females whose mentor's h index was in the top quartile were nearly 3 times as likely to receive a major grant as those whose mentors were in the bottom quartile (38.7% versus 13.3%).</p> <p>Conclusions</p> <p>Sixteen years after starting their PD, only 9% of males had dropped out of science. More females (28%) have dropped out of science, primarily because fewer went into industry positions. The mentor's publication record does not affect the future grant success of males but it has a dramatic effect on female grant success.</p

Keldysh technique and non-linear sigma-model: basic principles and applications

The purpose of this review is to provide a comprehensive pedagogical introduction into Keldysh technique for interacting out-of-equilibrium fermionic and bosonic systems. The emphasis is placed on a functional integral representation of underlying microscopic models. A large part of the review is devoted to derivation and applications of the non-linear sigma-model for disordered metals and superconductors. We discuss such topics as transport properties, mesoscopic effects, counting statistics, interaction corrections, kinetic equation, etc. The sections devoted to disordered superconductors include Usadel equation, fluctuation corrections, time-dependent Ginzburg-Landau theory, proximity and Josephson effects, etc. (This review is a substantial extension of arXiv:cond-mat/0412296.)Comment: Review: 103 pages, 19 figure

A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis