Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein–Induced Retinal AngiogenesisHighlights

OBJECTIVE: Increasing evidence suggests that bone morphogenetic protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early postnatal angiogenesis by analysis of inducible, endothelial-specific deletion of the BMP receptor components Bmpr2 (BMP type 2 receptor), Alk1 (activin receptor-like kinase 1), Alk2, and Alk3 in mouse retinal vessels. APPROACH AND RESULTS: Expression analysis of several BMP ligands showed that proangiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of Bmpr2. Postnatal deletion of Bmpr2 in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branch points behind the front, leading to attenuated radial expansion. To identify critical BMPR1s (BMP type 1 receptors) associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of 3 BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial-specific deletion of either Alk2/acvr1 or Alk3/Bmpr1a caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial-specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for proangiogenic BMP signaling in retinal vessels. CONCLUSIONS: Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential proangiogenic cue for retinal vessels

The effect of telehealth on quality of life and psychological outcomes over a 12-month period in a diabetic cohort within the Whole Systems Demonstrator cluster randomised trial

Background: Much is written about the promise of telehealth and there is great enthusiasm about its potential. However, many studies of telehealth do not meet orthodox quality standards and there are few studies examining quality of life in diabetes as an outcome. Objective: To assess the impact of home-based telehealth (remote monitoring of physiological, symptom and self-care behavior data for long-term conditions) on generic and disease-specific health-related quality of life, anxiety, and depressive symptoms over 12 months in patients with diabetes. Remote monitoring provides the potential to improve quality of life, through the reassurance it provides patients. Methods: The study focused on participant-reported outcomes of patients with diabetes within the Whole Systems Demonstrator (WSD) Telehealth Questionnaire Study, nested within a pragmatic cluster-randomized trial of telehealth (the WSD Telehealth Trial), held across 3 regions of England. Telehealth was compared with usual-care, with general practice as the unit of randomization. Participant-reported outcome measures (ShortForm 12, EuroQual-5D, Diabetes Health Profile scales, Brief State-Trait Anxiety Inventory, and Centre for Epidemiological Studies Depression Scale) were collected at baseline, short-term (4 months) and long-term (12months) follow-ups. Intention-to-treat analyses testing treatment effectiveness, were conducted using multilevel models controlling for practice clustering and a range of covariates. Analyses assumed participants received their allocated treatment and were conducted for participants who completed the baseline plus at least one follow-up assessment (n=317). Results: Primary analyses showed differences between telehealth and usual care were small and only reached significance for 1 scale [dibetes health profile-disinhibited eating, P=.006). The magnitude of differences between trial arms did not reach the trial-defined minimal clinically important difference of 0.3 standard deviations for any outcome. Effect sizes (Hedge's g) ranged from 0.015 to 0.143 for Generic quality of life (QoL) measures and 0.018 to 0.394 for disease specific measures. Conclusions: Second generation home-based telehealth as implemented in the WSD evaluation was not effective in the subsample of people with diabetes. Overall, telehealth did not improve or have a deleterious effect quality of life or psychological outcomes for patients with diabetes over a 12-month period

A mobile telehealth intervention for adults with insulin-requiring diabetes: early results of a mixed-methods randomized controlled trial

BACKGROUND: The role of technology in health care delivery has grown rapidly in the last decade. The potential of mobile telehealth (MTH) to support patient self-management is a key area of research. Providing patients with technological tools that allow for the recording and transmission of health parameters to health care professionals (HCPs) may promote behavior changes that result in improved health outcomes. Although for some conditions the evidence of the effectiveness of MTH is clear, to date the findings on the effects of MTH on diabetes management remain inconsistent. OBJECTIVE: This study aims to evaluate an MTH intervention among insulin-requiring adults with diabetes to establish whether supplementing standard care with MTH results in improved health outcomes-glycated hemoglobin (HbA1c), blood pressure (BP), health-related quality of life (HRQoL), diabetes self-management behaviors, diabetes health care utilization, and diabetes self-efficacy and illness beliefs. An additional objective was to explore the acceptability of MTH and patients' perceptions of, and experience, using it. METHODS: A mixed-method design consisting of a 9-month, two-arm, parallel randomized controlled trial (RCT) was used in combination with exit qualitative interviews. Quantitative data was collected at baseline, 3 months, and 9 months. Additional intervention fidelity data, such as participants' MTH transmissions and contacts with the MTH nurse during the study, were also recorded. RESULTS: Data collection for both the quantitative and qualitative components of this study has ended and data analysis is ongoing. A total of 86 participants were enrolled into the study. Out of 86 participants, 45 (52%) were randomized to the intervention group and 36 (42%) to the control group. Preliminary data on MTH training sessions and MTH usage by intervention participants are presented in this paper. We expect to publish complete study results in 2015. CONCLUSIONS: The range of data collected in this study will allow for a comprehensive evaluation of processes and outcomes. The early results presented suggest that MTH usage decreases over time and that MTH participants would benefit from attending more than one training session. TRIAL REGISTRATION: ClinicalTrials.gov NCT00922376; http://clinicaltrials.gov/ct2/show/NCT00922376 (Archived by WebCite at http://www.webcitation.org/6Vu4nhLI6)

The DARE study of relapse prevention in depression: design for a phase 1/2 translational randomised controlled trial involving mindfulness-based cognitive therapy and supported self monitoring

<p>Abstract</p> <p>Background</p> <p>Depression is a common condition that typically has a relapsing course. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition. Mindfulness-based cognitive therapy (MBCT) is a group-based intervention that has shown efficacy in reducing depressive relapse. While trials of MBCT to date have met the core requirements of phase 1 translational research, there is a need now to move to phase 2 translational research - the application of MBCT within real-world settings with a view to informing policy and clinical practice. The aim of this trial is to examine the clinical impact and health economics of MBCT under real-world conditions and where efforts have been made to assess for and prevent resentful demoralization among the control group. Secondary aims of the project involve extending the phase 1 agenda to an examination of the effects of co-morbidity and mechanisms of action.</p> <p>Methods/Design</p> <p>This study is designed as a prospective, multi-site, single-blind, randomised controlled trial using a group comparison design between involving the intervention, MBCT, and a self-monitoring comparison condition, Depression Relapse Active Monitoring (DRAM). Follow-up is over 2 years. The design of the study indicates recruitment from primary and secondary care of 204 participants who have a history of 3 or more episodes of Major Depression but who are currently well. Measures assessing depressive relapse/recurrence, time to first clinical intervention, treatment expectancy and a range of secondary outcomes and process variables are included. A health economics evaluation will be undertaken to assess the incremental cost of MBCT.</p> <p>Discussion</p> <p>The results of this trial, including an examination of clinical, functional and health economic outcomes, will be used to assess the role that this treatment approach may have in recommendations for treatment of depression in Australia and elsewhere. If the findings are positive, we expect that this research will consolidate the evidence base to guide the decision to fund MBCT and to seek to promote its availability to those who have experienced at least 3 episodes of depression.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry: <a href="http://www.anzctr.org.au/ACTRN12607000166471.aspx">ACTRN12607000166471</a></p

Phylogenetic Position of a Copper Age Sheep (Ovis aries) Mitochondrial DNA

BACKGROUND: Sheep (Ovis aries) were domesticated in the Fertile Crescent region about 9,000-8,000 years ago. Currently, few mitochondrial (mt) DNA studies are available on archaeological sheep. In particular, no data on archaeological European sheep are available. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the first portion of mtDNA sequence of a Copper Age European sheep. DNA was extracted from hair shafts which were part of the clothes of the so-called Tyrolean Iceman or Ötzi (5,350-5,100 years before present). Mitochondrial DNA (a total of 2,429 base pairs, encompassing a portion of the control region, tRNA(Phe), a portion of the 12S rRNA gene, and the whole cytochrome B gene) was sequenced using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products. We have compared the sequence with the corresponding sequence of 334 extant lineages. CONCLUSIONS/SIGNIFICANCE: A phylogenetic network based on a new cladistic notation for the mitochondrial diversity of domestic sheep shows that the Ötzi's sheep falls within haplogroup B, thus demonstrating that sheep belonging to this haplogroup were already present in the Alps more than 5,000 years ago. On the other hand, the lineage of the Ötzi's sheep is defined by two transitions (16147, and 16440) which, assembled together, define a motif that has not yet been identified in modern sheep populations

Rethinking Cultural Relations and Exchange in the Critical Zone

Chapter for Managing Culture: Reflecting on Exchange in our Global Times, book edited by Raphaela Henze and Victoria Durrer, to be published by Palgrave: Sociology of the Arts

Cysteinyl-tRNA Deacylation Can Be Uncoupled from Protein Synthesis

Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNACys

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin