Boosting advice and knowledge sharing among healthcare professionals

Purpose: This study investigates the dynamics of knowledge sharing in healthcare, exploring some of the factors that are more likely to influence the evolution of idea sharing and advice seeking in healthcare. Design/methodology/approach: We engaged 50 pediatricians representing many subspecialties at a mid-size US children's hospital using a social network survey to map and measure advice seeking and idea sharing networks. Through the application of Stochastic Actor-Oriented Models, we compared the structure of the two networks prior to a leadership program and eight weeks post conclusion. Findings: Our models indicate that healthcare professionals carefully and intentionally choose with whom they share ideas and from whom to seek advice. The process is fluid, non-hierarchical and open to changing partners. Significant transitivity effects indicate that the processes of knowledge sharing can be supported by mediation and brokerage. Originality: Hospital administrators can use this method to assess knowledge-sharing dynamics, design and evaluate professional development initiatives, and promote new organizational structures that break down communication silos. Our work contributes to the literature on knowledge sharing in healthcare by adopting a social network approach, going beyond the dyadic level, and assessing the indirect influence of peers' relationships on individual networks

Feasibility study of peer-led and school-based social network Intervention (STASH) to promote adolescent sexual health.

BACKGROUND: Effective sex education is the key to good sexual health. Peer-led approaches can augment teacher-delivered sex education, but many fail to capitalise on mechanisms of social influence. We assessed the feasibility of a novel intervention (STASH) in which students (aged 14-16) nominated as influential by their peers were recruited and trained as Peer Supporters (PS). Over a 5-10-week period, they spread positive sexual health messages to friends in their year group, both in-person and via social media, and were supported to do so via weekly trainer-facilitated meetings. The aims of the study were to assess the feasibility of STASH (acceptability, fidelity and reach), to test and refine the programme theory and to establish whether the study met pre-set progression criteria for continuation to larger-scale evaluation. METHODS: The overall design was a non-randomised feasibility study of the STASH intervention in 6 schools in Scotland. Baseline (n=680) and follow-up questionnaires (approx. 6 months later; n=603) were administered to the intervention year group. The control group (students in year above) completed the follow-up questionnaire only (n=696), 1 year before the intervention group. The PS (n=88) completed a brief web survey about their experience of the role; researchers interviewed participants in key roles (PS (n=20); PS friends (n=22); teachers (n=8); trainers (n=3)) and observed 20 intervention activities. Activity evaluation forms and project monitoring data also contributed information. We performed descriptive quantitative analysis and thematic qualitative analysis. RESULTS: The PS role was acceptable; on average across schools >50% of students nominated as influential by their friends, signed up and were trained (n=104). This equated to 13% of the year group. Trained PS rarely dropped out (97% completion rate) and 85% said they liked the role. Fidelity was good (all bar one trainer-led activity carried out; PS were active). The intervention had good reach; PS were reasonably well connected and perceived as 'a good mix' and 58% of students reported exposure to STASH. Hypothesised pre-conditions, contextual influences and mechanisms of change for the intervention were largely confirmed. All bar one of the progression criteria was met. CONCLUSION: The weight of evidence supports continuation to full-scale evaluation. TRIAL REGISTRATION: Current controlled trials ISRCTN97369178

Peer-led intervention to prevent and reduce STI transmission and improve sexual health in secondary schools (STASH): protocol for a feasibility study

Background: Young people in the UK are at highest risk of sexually transmitted infections and report higher levels of unsafe sex than any other age group. Involving peer supporters in intervention delivery is acceptable to students and effective in reducing risk behaviours via ‘diffusion of innovation’, particularly where peer supporters are influential in their networks. Informal peer-led interventions offer a useful alternative to peer-led didactic teaching, which has shown limited effects. Building on the successful ASSIST anti-smoking intervention, the ‘STis And Sexual Health’ (STASH) intervention involves identification and recruitment of the most influential students as peer supporters, training and support to these students by specialist trainers, positive sex and relationships messages, spread by peer supporters to their friendship groups in person and via social media. Methods/design: This protocol describes a feasibility trial of the STASH intervention in six schools. It builds on an earlier study phase of intervention co-development using patient and public involvement (PPI) activities, followed by a pilot of intervention components and evaluation tools in one school. Participants are fourth year (S4) students (aged 14–16) in state-funded Scottish secondary schools who have received some level of teacher-led sex education. The previous cohort of S4 students (those completing S4 in the year prior to the intervention) will serve as controls. Data will be collected from controls (month 16), baseline (month 20–21) and follow-up (month 27–30) via a web-based questionnaire, which will measure (and test the reliability of) primary outcome measures for a phase III trial (delayed initiation of/abstinence from sex and consistent condom use), secondary outcomes and mediators of sexual behaviour (including school climate and social networks). The main feasibility outcome is whether the study meets pre-set progression criteria regarding feasibility and acceptability, measured largely via a process evaluation (basic measures in all 6 schools and in-depth in 2-4 schools). An economic evaluation reporting costs alongside consequences will be conducted. Discussion: This study will inform decisions on the feasibility, design and sample size for a phase III effectiveness trial to assess whether the STASH intervention is effective in reducing the risk of sexually transmitted infections in young people

Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.

By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range

Preserving mobility in older adults with physical frailty and sarcopenia: Opportunities, challenges, and recommendations for physical activity interventions

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move indepen-dently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature

Isozyme-Specific Ligands for O-acetylserine sulfhydrylase, a Novel Antibiotic Target

Conceived and designed the experiments: FS PC BC ES AM. Performed the experiments: FS RS ES PF SR. Analyzed the data: FS BC ES PF GEK PFC AM. Contributed reagents/materials/analysis tools: PC PB GC. Wrote the paper: FS GEK BC AM.The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block bacterial cysteine biosynthesis.Yeshttp://www.plosone.org/static/editorial#pee