Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues.

The use of Assay for Transposase-Accessible Chromatin (ATAC-seq) to profile chromatin accessibility has surged over the past years, but its applicability to tissues has been very limited. With the intent of preserving nuclear architecture during long-term storage, cryopreserved nuclei preparations from chicken lung were used to optimize ATAC-seq. Sequencing data were compared with existing DNase-seq, ChIP-seq, and RNA-seq data to evaluate library quality, ultimately resulting in a modified ATAC-seq method capable of generating high quality chromatin accessibility data from cryopreserved nuclei preparations. Using this method, nucleosome-free regions (NFR) identified in chicken lung overlapped half of DNase-I hypersensitive sites, coincided with active histone modifications, and specifically marked actively expressed genes. Notably, sequencing only the subnucleosomal fraction dramatically improved signal, while separation of subnucleosomal reads post-sequencing did not improve signal or peak calling. The broader applicability of this modified ATAC-seq technique was tested using cryopreserved nuclei preparations from pig tissues, resulting in NFR that were highly consistent among biological replicates. Furthermore, tissue-specific NFR were enriched for binding motifs of transcription factors related to tissue-specific functions, and marked genes functionally enriched for tissue-specific processes. Overall, these results provide insights into the optimization of ATAC-seq and a platform for profiling open chromatin in animal tissues

Development of a best practice statement on the use of ankle-foot orthoses following stroke in Scotland

A National Health Service Quality Improvement Scotland (NHS QIS) scoping exercise in 2007 identified the use of ankle-foot orthoses (AFOs) following stroke as a clinical improvement priority, leading to the development of a best practice statement (BPS) on AFO use after stroke. This paper outlines the development process of the BPS which is available from NHS QIS. The authors were involved in the development of the BPS as part of a working group that included practitioners from the fields of orthotics, physiotherapy, stroke nursing and bioengineering, and staff of NHS QIS and a patient representative. In consultation with an NHS QIS health services researcher, the authors undertook a systematic literature review to evidence where possible the recommendations made in the BPS. Where evidence was unavailable, consensus was reached by the expert working group. As the BPS was designed for the non-specialist and non-orthotic practitioner the authors also developed educational resources which were included within the BPS to aid the understanding of the principles underpinning orthotic design and prescription. The BPS has been widely distributed throughout the health service in Scotland and is available electronically at no cost via the NHS QIS website. At part of an ongoing evaluation of the impact of the BPS on the quality of orthotic provision, NHS QIS has invited feedback regarding successes and challenges to implementation

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Distributive Justice and the Crime Drop

Data were extracted from a total of almost 600000 respondents from all sweeps of the Crime Survey for England and Wales (CSEW) 1982-2012 to determine whether victimisation was more or less concentrated across households during the crime drop. The most victimised household decile experienced the greatest absolute decline in victimisation but still accounted for over 70% of all victimisations suffered. Methodological issues underlying the patterns observed are discussed. The characteristics associated with highly victimised household are consistent across survey sweeps. Cross-national and crime type extension of work of the kind undertaken is advocated as both intrinsically important and likely to clarify the dynamics of the crime drop

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Tuning supersymmetric models at the LHC: A comparative analysis at two-loop level

We provide a comparative study of the fine tuning amount (Delta) at the two-loop leading log level in supersymmetric models commonly used in SUSY searches at the LHC. These are the constrained MSSM (CMSSM), non-universal Higgs masses models (NUHM1, NUHM2), non-universal gaugino masses model (NUGM) and GUT related gaugino masses models (NUGMd). Two definitions of the fine tuning are used, the first (Delta_{max}) measures maximal fine-tuning wrt individual parameters while the second (Delta_q) adds their contribution in "quadrature". As a direct result of two theoretical constraints (the EW minimum conditions), fine tuning (Delta_q) emerges as a suppressing factor (effective prior) of the averaged likelihood (under the priors), under the integral of the global probability of measuring the data (Bayesian evidence p(D)). For each model, there is little difference between Delta_q, Delta_{max} in the region allowed by the data, with similar behaviour as functions of the Higgs, gluino, stop mass or SUSY scale (m_{susy}=(m_{\tilde t_1} m_{\tilde t_2})^{1/2}) or dark matter and g-2 constraints. The analysis has the advantage that by replacing any of these mass scales or constraints by their latest bounds one easily infers for each model the value of Delta_q, Delta_{max} or vice versa. For all models, minimal fine tuning is achieved for M_{higgs} near 115 GeV with a Delta_q\approx Delta_{max}\approx 10 to 100 depending on the model, and in the CMSSM this is actually a global minimum. Due to a strong ($\approx$ exponential) dependence of Delta on M_{higgs}, for a Higgs mass near 125 GeV, the above values of Delta_q\approx Delta_{max} increase to between 500 and 1000. Possible corrections to these values are briefly discussed.Comment: 23 pages, 46 figures; references added; some clarifications (section 2

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Psychological interventions in asthma

Asthma is a multifactorial chronic respiratory disease characterised by recurrent episodes of airway obstruction. The current management of asthma focuses principally on pharmacological treatments, which have a strong evidence base underlying their use. However, in clinical practice, poor symptom control remains a common problem for patients with asthma. Living with asthma has been linked with psychological co-morbidity including anxiety, depression, panic attacks and behavioural factors such as poor adherence and suboptimal self-management. Psychological disorders have a higher-than-expected prevalence in patients with difficult-to-control asthma. As psychological considerations play an important role in the management of people with asthma, it is not surprising that many psychological therapies have been applied in the management of asthma. There are case reports which support their use as an adjunct to pharmacological therapy in selected individuals, and in some clinical trials, benefit is demonstrated, but the evidence is not consistent. When findings are quantitatively synthesised in meta-analyses, no firm conclusions are able to be drawn and no guidelines recommend psychological interventions. These inconsistencies in findings may in part be due to poor study design, the combining of results of studies using different interventions and the diversity of ways patient benefit is assessed. Despite this weak evidence base, the rationale for psychological therapies is plausible, and this therapeutic modality is appealing to both patients and their clinicians as an adjunct to conventional pharmacological treatments. What are urgently required are rigorous evaluations of psychological therapies in asthma, on a par to the quality of pharmaceutical trials. From this evidence base, we can then determine which interventions are beneficial for our patients with asthma management and more specifically which psychological therapy is best suited for each patient

Reproductive health issues emanating from the Children’s Act No. 38 of 2005 as amended in 2008: A pilot study of the rights of parents versus rights of children

The study took as its point of departure the Children’s Act No, 38 of 2005 implemented in 2010, which aims to promote the preservation and strengthening of families and to give effect to the rights of children as enshrined in the Constitution of the Republic of South Africa. When the Act was introduced certain segments of society applauded the government for its efforts to promote the rights of children, while others condemned the government’s approach towards parents’ rights in relation to reproductive health issues affecting their children. The primary aim of the research project was to explore the views of a group of parents in Johannesburg Metro Region 11 regarding reproductive health care as embedded in the Children’s Act. A small-scale, descriptive, cross-sectional pilot research design was employed which involved individual interviews with 35 participants. The main findings that emerged from the study were that participants did not participate in the process leading up to the promulgation of the Act and consequently had little knowledge about the Act or its objectives. The fact that participants did not support certain clauses on reproductive health care and were of the opinion that their rights as parents were being violated has implications for amendment of the Act