223 research outputs found

    Participant recruitment to FiCTION, a primary dental care trial – survey of facilitators and barriers

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    Objective To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). Subjects (materials) and methods An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. Results Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. Conclusions These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team

    Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome

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    Protein synthesis is catalyzed in the peptidyl transferase center (PTC), located in the large (50S) subunit of the ribosome. No high-resolution structure of the intact ribosome has contained a complete active site including both A- and P-site tRNAs. In addition, although past structures of the 50S subunit have found no ordered proteins at the PTC, biochemical evidence suggests that specific proteins are capable of interacting with the 3′ ends of tRNA ligands. Here we present structures, at 3.6-Å and 3.5-Å resolution respectively, of the 70S ribosome in complex with A- and P-site tRNAs that mimic pre- and post-peptidyl-transfer states. These structures demonstrate that the PTC is very similar between the 50S subunit and the intact ribosome. They also reveal interactions between the ribosomal proteins L16 and L27 and the tRNA substrates, helping to elucidate the role of these proteins in peptidyl transfer

    Children’s perceptions of dissimilarity in parenting styles are associated with internalizing and externalizing behavior

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    The purpose of this study was to examine the relationship between children’s perception of dissimilarity in parenting styles, and internalizing and externalizing problems in children. Children from the general population (n = 658) reported on the level of emotional warmth, rejection, and overprotection of both parents by filling out the child version of the Egna Minnen Beträffande Uppfostran (EMBU-C) and mothers completed the child behavior checklist (CBCL). Intraclass correlations were computed as measures of dissimilarity between parenting styles of mothers and fathers. Children’s perceived dissimilarity in parental emotional warmth is associated with internalizing and externalizing problems (β = 0.092, p < 0.05; β = 0.091, p < 0.05). Perceived dissimilarity between parents’ overprotection is associated with externalizing problems (β = 0.097, p < 0.05). Perceived dissimilarity between parenting styles is associated with externalizing and internalizing problems, over and above the effects of the level of the parenting styles. The results highlight the negative consequences of perceived dissimilarity between parents. To conclude, children have more internalizing and externalizing problems when they perceive their parents as more dissimilar in parenting styles

    Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

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    A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

    Organizational interventions employing principles of complexity science have improved outcomes for patients with Type II diabetes

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    <p>Abstract</p> <p>Background</p> <p>Despite the development of several models of care delivery for patients with chronic illness, consistent improvements in outcomes have not been achieved. These inconsistent results may be less related to the content of the models themselves, but to their underlying conceptualization of clinical settings as linear, predictable systems. The science of complex adaptive systems (CAS), suggests that clinical settings are non-linear, and increasingly has been used as a framework for describing and understanding clinical systems. The purpose of this study is to broaden the conceptualization by examining the relationship between interventions that leverage CAS characteristics in intervention design and implementation, and effectiveness of reported outcomes for patients with Type II diabetes.</p> <p>Methods</p> <p>We conducted a systematic review of the literature on organizational interventions to improve care of Type II diabetes. For each study we recorded measured process and clinical outcomes of diabetic patients. Two independent reviewers gave each study a score that reflected whether organizational interventions reflected one or more characteristics of a complex adaptive system. The effectiveness of the intervention was assessed by standardizing the scoring of the results of each study as 0 (no effect), 0.5 (mixed effect), or 1.0 (effective).</p> <p>Results</p> <p>Out of 157 potentially eligible studies, 32 met our eligibility criteria. Most studies were felt to utilize at least one CAS characteristic in their intervention designs, and ninety-one percent were scored as either "mixed effect" or "effective." The number of CAS characteristics present in each intervention was associated with effectiveness (p = 0.002). Two individual CAS characteristics were associated with effectiveness: interconnections between participants and co-evolution.</p> <p>Conclusion</p> <p>The significant association between CAS characteristics and effectiveness of reported outcomes for patients with Type II diabetes suggests that complexity science may provide an effective framework for designing and implementing interventions that lead to improved patient outcomes.</p

    A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria

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    <p>Abstract</p> <p>Background</p> <p>An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by <it>Plasmodium falciparum</it>. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.</p> <p>Methods</p> <p>Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for <it>pfmdr1</it>, <it>pfcrt</it>, <it>dhfr</it>, <it>dhps</it>, gene copy number for <it>pfmdr1</it>) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95<sup>th </sup>confidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.</p> <p>Results</p> <p>92 studies were eligible among the selection from computerized search, with information on <it>pfcrt </it>(25/159 studies), <it>pfmdr1 </it>(29/236 studies), <it>dhfr </it>(18/373 studies), <it>dhps </it>(20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of <it>pfcrt </it>K76T (Day 28, OR = 7.2 [95%CI: 4.5–11.5]), <it>pfmdr1 </it>N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3–2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6–11.3, p < 0.001]). For sulphadoxine-pyrimethamine the <it>dhfr </it>single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9–6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0–4.9]) and <it>dhfr</it>-<it>dhps </it>quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2–8.8]) also increased the risk of treatment failure. Increased <it>pfmdr1 </it>copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3–22.9]).</p> <p>Conclusion</p> <p>When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.</p

    Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells

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    Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS

    The burden and treatment of HIV in tuberculosis patients in Papua Province, Indonesia: a prospective observational study

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    <p>Abstract</p> <p>Background</p> <p>New diagnoses of tuberculosis (TB) present important opportunities to detect and treat HIV. Rates of HIV and TB in Indonesia's easternmost Papua Province exceed national figures, but data on co-infection rates and outcomes are lacking. We aimed to measure TB-HIV co-infection rates, examine longitudinal trends, compare management with World Health Organisation (WHO) recommendations, and document progress and outcome.</p> <p>Methods</p> <p>Adults with newly-diagnosed smear-positive pulmonary TB managed at the Timika TB clinic, Papua Province, were offered voluntary counselling and testing for HIV in accordance with Indonesian National Guidelines, using a point-of-care antibody test. Positive tests were confirmed with 2 further rapid tests. Study participants were assessed using clinical, bacteriological, functional and radiological measures and followed up for 6 months.</p> <p>Results</p> <p>Of 162 participants, HIV status was determined in 138 (85.2%), of whom 18 (13.0%) were HIV+. Indigenous Papuans were significantly more likely to be HIV+ than Non-Papuans (Odds Ratio [OR] 4.42, 95% confidence interval [CI] 1.38-14.23). HIV prevalence among people with TB was significantly higher than during a 2003-4 survey at the same TB clinic, and substantially higher than the Indonesian national estimate of 3%. Compared with HIV- study participants, those with TB-HIV co-infection had significantly lower exercise tolerance (median difference in 6-minute walk test: 25 m, p = 0.04), haemoglobin (mean difference: 1.3 g/dL, p = 0.002), and likelihood of cavitary disease (OR 0.35, 95% CI 0.12-1.01), and increased occurrence of pleural effusion (OR 3.60, 95% CI 1.70-7.58), higher rates of hospitalisation or death (OR 11.80, 95% CI 1.82-76.43), but no difference in the likelihood of successful 6-month treatment outcome. Adherence to WHO guidelines was limited by the absence of integration of TB and HIV services, specifically, with no on-site ART prescriber available. Only six people had CD4+ T-cell counts recorded, 11 were prescribed co-trimoxazole and 4 received ART before, during or after TB treatment, despite ART being indicated in 14 according to 2006 WHO guidelines.</p> <p>Conclusions</p> <p>TB-HIV co-infection in southern Papua, Indonesia, is a serious emerging problem especially among the Indigenous population, and has risen rapidly in the last 5 years. Major efforts are required to incorporate new WHO recommendations on TB-HIV management into national guidelines, and support their implementation in community settings.</p

    Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

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    Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory

    Postpartum psychiatric disorders

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    Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential
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