The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

Background: Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design: The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion: This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration: ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder

Behavior Change without Behavior Change Communication: Nudging Handwashing among Primary School Students in Bangladesh.

Behavior change communication for improving handwashing with soap can be labor and resource intensive, yet quality results are difficult to achieve. Nudges are environmental cues engaging unconscious decision-making processes to prompt behavior change. In this proof-of-concept study, we developed an inexpensive set of nudges to encourage handwashing with soap after toilet use in two primary schools in rural Bangladesh. We completed direct observation of behaviors at baseline, after providing traditional handwashing infrastructure, and at multiple time periods following targeted handwashing nudges (1 day, 2 weeks, and 6 weeks). No additional handwashing education or motivational messages were completed. Handwashing with soap among school children was low at baseline (4%), increasing to 68% the day after nudges were completed and 74% at both 2 weeks and 6 weeks post intervention. Results indicate that nudge-based interventions have the potential to improve handwashing with soap among school-aged children in Bangladesh and specific areas of further inquiry are discussed

BC4707 Is a Major Facilitator Superfamily Multidrug Resistance Transport Protein from Bacillus cereus Implicated in Fluoroquinolone Tolerance

Transcriptional profiling highlighted a subset of genes encoding putative multidrug transporters in the pathogen Bacillus cereus that were up-regulated during stress produced by bile salts. One of these multidrug transporters (BC4707) was selected for investigation. Functional characterization of the BC4707 protein in Escherichia coli revealed a role in the energized efflux of xenobiotics. Phenotypic analyses after inactivation of the gene bc4707 in Bacillus cereus ATCC14579 suggested a more specific, but modest role in the efflux of norfloxacin. In addition to this, transcriptional analyses showed that BC4707 is also expressed during growth of B. cereus under non-stressful conditions where it may have a role in the normal physiology of the bacteria. Altogether, the results indicate that bc4707, which is part of the core genome of the B. cereus group of bacteria, encodes a multidrug resistance efflux protein that is likely involved in maintaining intracellular homeostasis during growth of the bacteria.Peer reviewe

Prevalence and correlates of self-reported state of teeth among schoolchildren in Kerala, India

BACKGROUND: Oral health status in India is traditionally evaluated using clinical indices. There is growing interest to know how subjective measures relate to outcomes of oral health. The aims of the study were to assess the prevalence and correlates of self-reported state of teeth in 12-year-old schoolchildren in Kerala, India. METHODS: Cross-sectional survey data were used. The sample consisted of 838 12-year-old schoolchildren. Data was collected using clinical examination and questionnaire. The clinical oral health status was recorded using Decayed, Missing and Filled Teeth (DMFT) and Oral Hygiene Index – Simplified (OHI-S). The questionnaire included questions on sociodemographics, self reports of behaviour, knowledge and oral problems and a single-item measuring self-reported state and satisfaction with appearance of teeth. The Kappa values for test-retest of the questionnaire ranged from 0.55 to 0.97. RESULTS: Twenty-three per cent of the schoolchildren reported the state of teeth as bad. Multivariate logistic regression showed significant associations between schoolchildren who reported to have bad teeth and poor school performance (Odds Ratio (OR) = 2.5), having bad breath (OR = 2.4), food impaction (OR = 1.7) dental visits (OR = 1.6), being dissatisfied with appearance of teeth (OR = 4.2) and caries experience (OR = 1.7). The explained variance was highest when the variables dental visits, bleeding gums, bad breath, food impaction and satisfaction with appearance were introduced into the model (19%). CONCLUSION: A quarter of 12-year-olds reported having bad teeth. The self-reported bad state of teeth was associated with poor school performance, having bad breath and food impaction, having visited a dentist, being dissatisfied with teeth appearance and having caries experience. Information from self-reports of children might help in planning effective strategies to promote oral health

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

The MFS efflux proteins of gram-positive and gram-negative bacteria

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Susceptibilities of <i>B. cereus</i> ATCC14579 (wild type) compared to its isogenic <i>Δbc4707</i> mutant.

§<p>represents the fold difference in MIC between the wild type <i>B. cereus</i> ATCC14579 and its isogenic <i>Δbc4707</i> mutant.</p