58 research outputs found

    Longitudinal Mediators of Relations Between Family Violence and Adolescent Dating Aggression Perpetration: Family Violence and Adolescent Dating Aggression

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    Few longitudinal studies have examined the pathways through which family violence leads to dating aggression. In the current study the authors used 3 waves of data obtained from 8th- and 9th-grade adolescents (N = 1,965) to examine the hypotheses that the prospective relationship between witnessing family violence and directly experiencing violence and physical dating aggression perpetration is mediated by 3 constructs: (a) normative beliefs about dating aggression (norms), (b) anger dysregulation, and (c) depression. Results from cross-lagged regression models suggest that the relationship between having been hit by an adult and dating aggression is mediated by changes in norms and anger dysregulation, but not depression. No evidence of indirect effects from witnessing family violence to dating aggression was found through any of the proposed mediators. Taken together, the findings suggest that anger dysregulation and normative beliefs are potential targets for dating abuse prevention efforts aimed at youth who have directly experienced violence

    Combination antisense treatment for destructive exon skipping of myostatin and open reading frame rescue of dystrophin in neonatal <i>mdx</i> mice

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    The fatal X-linked Duchenne muscular dystrophy (DMD), characterized by progressive muscle wasting and muscle weakness, is caused by mutations within the DMD gene. The use of antisense oligonucleotides (AOs) modulating pre-mRNA splicing to restore the disrupted dystrophin reading frame, subsequently generating a shortened but functional protein has emerged as a potential strategy in DMD treatment. AO therapy has recently been applied to induce out-of-frame exon skipping of myostatin pre-mRNA, knocking-down expression of myostatin protein, and such an approach is suggested to enhance muscle hypertrophy/hyperplasia and to reduce muscle necrosis. Within this study, we investigated dual exon skipping of dystrophin and myostatin pre-mRNAs using phosphorodiamidate morpholino oligomers conjugated with an arginine-rich peptide (B-PMOs). Intraperitoneal administration of B-PMOs was performed in neonatal mdx males on the day of birth, and at weeks 3 and 6. At week 9, we observed in treated mice (as compared to age-matched, saline-injected controls) normalization of muscle mass, a recovery in dystrophin expression, and a decrease in muscle necrosis, particularly in the diaphragm. Our data provide a proof of concept for antisense therapy combining dystrophin restoration and myostatin inhibition for the treatment of DMD

    Reporting transparency and completeness in trials : Paper 3 – trials conducted using administrative databases do not adequately report elements related to use of databases

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    Acknowledgments The development of CONSORT-ROUTINE and the present review were funded by grants from the Canadian Institutes of Health Research (PI Thombs, #PJT-156172; PIs Thombs and Kwakkenbos, #PCS-161863) and from the United Kingdom National Institute of Health Research (NIHR) Clinical Trials Unit Support Funding (PI Juszczak, Co-PI Gale, supported salary of SM). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Dr. Langan was supported by a Wellcome Senior Clinical Fellowship in Science (205039/Z/16/Z). Dr. Moher is supported by a University Research Chair (uOttawa). Dr. Gale was supported by the United Kingdom Medical Research Council through a Clinician Scientist Fellowship. Dr. Thombs was supported by a Tier 1 Canada Research Chair.Peer reviewedPublisher PD

    Protocol for a scoping review to support development of a CONSORT extension for randomised controlled trials using cohorts and routinely collected health data.

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    INTRODUCTION: Randomised controlled trials (RCTs) conducted using cohorts and routinely collected health data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. The development of an extension of the CONsolidated Standards of Reporting Trials (CONSORT) statement for RCTs using cohorts and routinely collected health data is being undertaken with the goal of improving reporting quality by setting standards early in the process of uptake of these designs. To develop this extension to the CONSORT statement, a scoping review will be conducted to identify potential modifications or clarifications of existing reporting guideline items, as well as additional items needed for reporting RCTs using cohorts and routinely collected health data. METHODS AND ANALYSIS: In separate searches, we will seek publications on methods or reporting or that describe protocols or results from RCTs using cohorts, registries, electronic health records and administrative databases. Data sources will include Medline and the Cochrane Methodology Register. For each of the four main types of RCTs using cohorts and routinely collected health data, separately, two investigators will independently review included publications to extract potential checklist items. A potential item will either modify an existing CONSORT 2010, Strengthening the Reporting of Observational Studies in Epidemiology or REporting of studies Conducted using Observational Routinely collected health Data item or will be proposed as a new item. Additionally, we will identify examples of good reporting in RCTs using cohorts and routinely collected health data. ETHICS AND DISSEMINATION: The proposed scoping review will help guide the development of the CONSORT extension statement for RCTs conducted using cohorts and routinely collected health data

    The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

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    On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

    Sodium ion interactions with aqueous glucose: Insights from quantum mechanics, molecular dynamics, and experiment

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    In the last several decades, significant efforts have been conducted to understand the fundamental reactivity of glucose derived from plant biomass in various chemical environments for conversion to renewable fuels and chemicals. For reactions of glucose in water, it is known that inorganic salts naturally present in biomass alter the product distribution in various deconstruction processes. However, the molecular-level interactions of alkali metal ions and glucose are unknown. These interactions are of physiological interest as well, for example, as they relate to cation-glucose cotransport. Here, we employ quantum mechanics (QM) to understand the interaction of a prevalent alkali metal, sodium, with glucose from a structural and thermodynamic perspective. The effect on B-glucose is subtle: a sodium ion perturbs bond lengths and atomic partial charges less than rotating a hydroxymethyl group. In contrast, the presence of a sodium ion significantly perturbs the partial charges of α-glucose anomeric and ring oxygens. Molecular dynamics (MD) simulations provide dynamic sampling in explicit water, and both the QM and the MD results show that sodium ions associate at many positions with respect to glucose with reasonably equivalent propensity. This promiscuous binding nature of Na + suggests that computational studies of glucose reactions in the presence of inorganic salts need to ensure thorough sampling of the cation positions, in addition to sampling glucose rotamers. The effect of NaCl on the relative populations of the anomers is experimentally quantified with light polarimetry. These results support the computational findings that Na + interacts similarly with a- and B-glucose

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    The impact of women's social position on fertility in developing countries

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    This paper examines ideas about possible ways in which the extent of women's autonomy, women's economic dependency, and other aspects of their position vis-à-vis men influence fertility in Third World populations. Women's position or “status” seems likely to be related to the supply of children because of its links with age at marriage. Women's position may also affect the demand for children and the costs of fertility regulation, though some connections suggested in the literature are implausible. The paper ends with suggestions for future research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45660/1/11206_2005_Article_BF01124382.pd
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