CSGM Designer: a platform for designing cross-species intron-spanning genic markers linked with genome information of legumes.

BackgroundGenetic markers are tools that can facilitate molecular breeding, even in species lacking genomic resources. An important class of genetic markers is those based on orthologous genes, because they can guide hypotheses about conserved gene function, a situation that is well documented for a number of agronomic traits. For under-studied species a key bottleneck in gene-based marker development is the need to develop molecular tools (e.g., oligonucleotide primers) that reliably access genes with orthology to the genomes of well-characterized reference species.ResultsHere we report an efficient platform for the design of cross-species gene-derived markers in legumes. The automated platform, named CSGM Designer (URL: http://tgil.donga.ac.kr/CSGMdesigner), facilitates rapid and systematic design of cross-species genic markers. The underlying database is composed of genome data from five legume species whose genomes are substantially characterized. Use of CSGM is enhanced by graphical displays of query results, which we describe as "circular viewer" and "search-within-results" functions. CSGM provides a virtual PCR representation (eHT-PCR) that predicts the specificity of each primer pair simultaneously in multiple genomes. CSGM Designer output was experimentally validated for the amplification of orthologous genes using 16 genotypes representing 12 crop and model legume species, distributed among the galegoid and phaseoloid clades. Successful cross-species amplification was obtained for 85.3% of PCR primer combinations.ConclusionCSGM Designer spans the divide between well-characterized crop and model legume species and their less well-characterized relatives. The outcome is PCR primers that target highly conserved genes for polymorphism discovery, enabling functional inferences and ultimately facilitating trait-associated molecular breeding

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

Mapping Alternative Impact: Alternative approaches to impact from co-produced research

No abstract available

Suicide & Supervision: Issues for Probation Practice

Suicides by offenders in the community have been relatively under-researched in comparison with prison suicides. This study examined in-depth the events and experiences of 28 service users under probation supervision, based on continuous records from the start of their sentence to their death by suicide. The study presents novel findings through mapping suicidal behaviour on to the probation supervision process, and demonstrates the complex pathways leading to suicide in this population.Key issues identified include missed appointments, the impact of legal proceedings,changes in supervision, and the importance of recording risk

A cluster randomized trial comparing deltamethrin and bendiocarb as insecticides for indoor residual spraying to control malaria on Bioko Island, Equatorial Guinea.

BACKGROUND: Indoor residual spraying (IRS) has been used on Bioko for malaria control since 2004. In 2013 the insecticide was changed from bendiocarb to deltamethrin. Shortly after this change, there was a marked increase in malaria prevalence on the island. This trial was carried out to compare the effectiveness of bendiocarb and deltamethrin for use in IRS on Bioko. METHODS: Twenty-four clusters of houses were randomized to receive IRS with either bendiocarb or deltamethrin. Approximately 3 months after the intervention, the prevalence of malaria and levels of haemoglobin were measured in children aged 2-14 years in each cluster. RESULTS: Prevalence of malaria in 2-14 year olds was lower in the bendiocarb arm (16.8, 95 % CI 11.1-24.7, N = 1374) than in the deltamethrin arm (23.2, 95 % CI 16.0-32.3, N = 1330) but this difference was not significant (p = 0.390), even after adjusting for covariates (p = 0.119). Mean haemoglobin in children was marginally higher in the bendiocarb clusters (11.6 g/dl, 95 % CI 11.5-11.8, N = 1326) than in the deltamethrin clusters (11.5 g/dl, 95 % CI 11.3-11.7, N = 1329). This difference was borderline significant after adjusting for covariates (p = 0.049). CONCLUSIONS: The results are suggestive of bendiocarb being more effective at preventing malaria on Bioko although evidence for this was weak. The results are likely due to the fact that local vectors remain fully susceptible to bendiocarb whereas subsequent tests have shown resistance to deltamethrin

An Opinion: Federal Judges Misconstrue Rule 704 (Or Is That an Impermissible Legal Conclusion)

This article addresses the need to formulate a uniform and predictable approach to the admissibility of expert opinion testimony which relates the law to the facts. First, it briefly discusses the history of expert opinion testimony. Second, it discusses, through a case analysis, the difficult, if not impossible task that courts have assumed in attempting to differentiate between two types of expert opinions: (1) those which are, by their nature, factual; and (2) those which require some level of legal analysis-directly relating the law to the facts of the case. Finally, this article suggests an alternative approach which is arguably more consistent with the goals of Article VII of the Federal Rules of Evidence

Pupil dilation as an index of preferred mutual gaze duration

Most animals look at each other to signal threat or interest. In humans, this social interaction is usually punctuated with brief periods of mutual eye contact. Deviations from this pattern of gazing behaviour generally make us feel uncomfortable and are a defining characteristic of clinical conditions such as autism or schizophrenia, yet it is unclear what constitutes normal eye contact. Here, we measured, across a wide range of ages, cultures and personality types, the period of direct gaze that feels comfortable and examined whether autonomic factors linked to arousal were indicative of people’s preferred amount of eye contact. Surprisingly, we find that preferred period of gaze duration is not dependent on fundamental characteristics such as gender, personality traits or attractiveness. However, we do find that subtle pupillary changes, indicative of physiological arousal, correlate with the amount of eye contact people find comfortable. Specifically, people preferring longer durations of eye contact display faster increases in pupil size when viewing another person than those preferring shorter durations. These results reveal that a person’s preferred duration of eye contact is signalled by physiological indices (pupil dilation) beyond volitional control that may play a modulatory role in gaze behaviour

Using self-management to control seizures

The aim of this study was to develop, deliver and evaluate the impact of an education intervention regarding lifestyle self-management in the control of seizures, health related quality of life (HRQoL), satisfaction with life and resilience for adults with epilepsy

Autism Spectrum Social Stories In Schools Trial (ASSSIST):study protocol for a feasibility randomised controlled trial analysing clinical and cost-effectiveness of Social Stories in mainstream schools

INTRODUCTION: Current evidence suggests that Social Stories can be effective in tackling problem behaviours exhibited by children with autism spectrum disorder. Exploring the meaning of behaviour from a child's perspective allows stories to provide social information that is tailored to their needs. Case reports in children with autism have suggested that these stories can lead to a number of benefits including improvements in social interactions and choice making in educational settings. METHODS AND ANALYSIS: The feasibility of clinical and cost-effectiveness of a Social Stories toolkit will be assessed using a randomised control framework. Participants (n=50) will be randomised to either the Social Stories intervention or a comparator group where they will be read standard stories for an equivalent amount of time. Statistics will be calculated for recruitment rates, follow-up rates and attrition. Economic analysis will determine appropriate measures of generic health and resource use categories for cost-effectiveness analysis. Qualitative analysis will ascertain information on perceptions about the feasibility and acceptability of the intervention. ETHICS AND DISSEMINATION: National Health Service Ethics Approval (NHS; ref 11/YH/0340) for the trial protocol has been obtained along with NHS Research and Development permission from Leeds and York Partnership NHS Foundation Trust. All adverse events will be closely monitored, documented and reported to the study Data Monitoring Ethics Committee. At least one article in a peer reviewed journal will be published and research findings presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN96286707

Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis