Semirelativistic stability of N-boson systems bound by 1/r pair potentials

We analyze a system of self-gravitating identical bosons by means of a semirelativistic Hamiltonian comprising the relativistic kinetic energies of the involved particles and added (instantaneous) Newtonian gravitational pair potentials. With the help of an improved lower bound to the bottom of the spectrum of this Hamiltonian, we are able to enlarge the known region for relativistic stability for such boson systems against gravitational collapse and to sharpen the predictions for their maximum stable mass.Comment: 11 pages, considerably enlarged introduction and motivation, remainder of the paper unchange

Renal impairment in a rural African antiretroviral programme

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited

Outcomes and risk factors associated with endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents.

OBJECTIVE: To describe outcomes of and risk factors for endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injection. DESIGN: Single-center, consecutive, case series and retrospective case-control study. PARTICIPANTS: Between January 1, 2009, and May 31, 2010, 16 vitreoretinal surgeons administered a total of 27 736 injections. During this period, 23 cases of presumed infectious endophthalmitis occurred. Each surgeon used his own preferred injection technique. INTERVENTION: Vitreous or aqueous tap, or both, with intravitreal antibiotic injection and subsequent topical antibiotic and steroid drops. MAIN OUTCOME MEASURES: Visual acuity, bladed lid speculum use, conjunctival displacement, hemisphere of injection, bevacizumab versus ranibizumab, and infectious organism. RESULTS: Seven of 23 cases had positive culture results; 3 grew coagulase-negative Staphylococcus. All cases had pain and vitritis on average 3.4 days (range, 1-6 days) after injection, with no difference between culture-positive and culture-negative groups. Eighteen (78%) of 23 cases had a hypopyon. Fifteen of 23 cases returned to baseline vision (±2 lines) within 3 months. Neither lid speculum use (0.10% vs. 0.066% in the no-use group; P = 0.27), conjunctival displacement (0.11% vs. 0.076% in the no-displacement group; P = 0.43), hemisphere of injection (0.11% superior vs. 0.079% inferior; P = 0.56), or bevacizumab versus ranibizumab (0.11% vs. 0.066%; P = 0.21) affected risk. Analysis of only culture-positive results yielded similar results. There was no statistically significant difference between the proportion of culture-negative cases after bevacizumab injection (83%) versus ranibizumab injection (55%; P = 0.13). CONCLUSIONS: Most patients in whom presumed infectious endophthalmitis develop after anti-VEGF injection regained baseline vision after treatment. Bladed lid speculum use, conjunctival displacement, hemisphere of injection, and type of anti-VEGF agent did not affect risk. No difference in culture-negative endophthalmitis rates was detected after bevacizumab versus ranibizumab injection. Neither the presence of pain, vitritis, decreased vision, hypopyon, nor the interval between injection and development of symptoms differentiate culture-positive from culture-negative cases. Because a subgroup of patients had poor outcomes, a low threshold for vitreous tap with intravitreal antibiotic injection may be warranted. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article

Unique tracheal fluid microRNA signature predicts response to FETO in patients with congenital diaphragmatic hernia

"Epub ahead of print 2015 Jan 5"OBJECTIVE AND BACKGROUND: Our objective was to determine the fetal in vivo microRNA signature in hypoplastic lungs of human fetuses with severe isolated congenital diaphragmatic hernia (CDH) and changes in tracheal and amniotic fluid of fetuses undergoing fetoscopic endoluminal tracheal occlusion (FETO) to reverse severe lung hypoplasia due to CDH. METHODS:: We profiled microRNA expression in prenatal human lungs by microarray analysis. We then validated this signature with real-time quantitative polymerase chain reaction in tracheal and amniotic fluid of CDH patients undergoing FETO. We further explored the role of miR-200b using semiquantitative in situ hybridization and immunohistochemistry for TGF-ß2 in postnatal lung sections. We investigated miR-200b effects on TGF-ß signaling using a SMAD-luciferase reporter assay and Western blotting for phospho-SMAD2/3 and ZEB-2 in cultures of human bronchial epithelial cells. RESULTS:: CDH lungs display an increased expression of 2 microRNAs: miR-200b and miR-10a as compared to control lungs. Fetuses undergoing FETO display increased miR-200 expression in their tracheal fluid at the time of balloon removal. Future survivors of FETO display significantly higher miR-200 expression than those with a limited response. miR-200b was expressed in bronchial epithelial cells and vascular endothelial cells. TGF-ß2 expression was lower in CDH lungs. miR-200b inhibited TGF-ß-induced SMAD signaling in cultures of human bronchial epithelial cells. CONCLUSIONS:: Human fetal hypoplastic CDH lungs have a specific miR-200/miR-10a signature. Survival after FETO is associated with increased miR-200 family expression. miR-200b overexpression in CDH lungs results in decreased TGF-ß/SMAD signaling

Coordination as a function of skill level in the gymnastics longswing

The purpose of this study was to investigate the nature of inter-joint coordination at different levels of skilled performance to: (1) distinguish learners who were successful versus unsuccessful in terms of their task performance; (2) investigate the pathways of change during the learning of a new coordination pattern and (3) examine how the learner’s coordination patterns relate to those of experts in the longswing gymnastics skill. Continuous relative phase of hip and shoulder joint motions was examined for longswings performed by two groups of novices, successful (n = 4) and unsuccessful (n = 4) over five practice sessions, and two expert gymnasts. Principal component analysis showed that during longswing positions where least continuous relative phase variability occurred for expert gymnasts, high variability distinguished the successful from the unsuccessful novice group. Continuous relative phase profiles of successful novices became more out-of-phase over practice and less similar to the closely in-phase coupling of the expert gymnasts. Collectively, the findings support the proposition that at the level in inter-joint coordination a technique emerges that facilitates successful performance but is not more like an expert’s movement coordination. This finding questions the appropriateness of inferring development towards a “gold champion” movement coordination

Focused Ion Beam Fabrication

Contains summary of research program and reports on four research projects.Charles Stark Draper Laboratory (Contract DL-H-225270)Hughes Research LaboratoriesInternational Business Machines, Inc. (Contract 456614)Nippon Telegraph and Telephone, Inc.U.S. Navy - Office of Naval Research (Contract N00014-84-K-0073)U.S. Department of Defense (Contract MDA903-85-C-0215)Hitachi Central Research Laborator

Toolkit of Approaches To Support Target-Focused Drug Discovery for Plasmodium falciparum Lysyl tRNA Synthetase

There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery is reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe the development of a toolkit to support the therapeutic exploitation of a promising target, lysyl tRNA synthetase (PfKRS). The toolkit includes resistant mutants to probe resistance mechanisms and on-target engagement for specific chemotypes; a hybrid KRS protein capable of producing crystals suitable for ligand soaking, thus providing high-resolution structural information to guide compound optimization; chemical probes to facilitate pulldown studies aimed at revealing the full range of specifically interacting proteins and thermal proteome profiling (TPP); as well as streamlined isothermal TPP methods to provide unbiased confirmation of on-target engagement within a biologically relevant milieu. This combination of tools and methodologies acts as a template for the development of future target-enabling packages

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society

Mutation of neuron-specific chromatin remodeling subunit BAF53b:rescue of plasticity and memory by manipulating actin remodeling

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53b Delta SB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53b Delta SB2 mice in an effort to rescue LTP and memory. BAF53b Delta SB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders

Vertical zonation of testate amoebae in the Elatia Mires, northern Greece : palaeoecological evidence for a wetland response to recent climate change or autogenic processes?

The Elatia Mires of northern Greece are unique ecosystems of high conservation value. The mires are climatically marginal and may be sensitive to changing hydroclimate, while northern Greece has experienced a significant increase in aridity since the late twentieth century. To investigate the impact of recent climatic change on the hydrology of the mires, the palaeoecological record was investigated from three near-surface monoliths extracted from two sites. Testate amoebae were analysed as sensitive indicators of hydrology. Results were interpreted using transfer function models to provide quantitative reconstructions of changing water table depth and pH. AMS radiocarbon dates and 210Pb suggest the peats were deposited within the last c. 50 years, but do not allow a secure chronology to be established. Results from all three profiles show a distinct shift towards a more xerophilic community particularly noted by increases in Euglypha species. Transfer function results infer a distinct lowering of water tables in this period. A hydrological response to recent climate change is a tenable hypothesis to explain this change; however other possible explanations include selective test decay, vertical zonation of living amoebae, ombrotrophication and local hydrological change. It is suggested that a peatland response to climatic change is the most probable hypothesis, showing the sensitivity of marginal peatlands to recent climatic change