A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Effect of broaching on high-temperature fatigue behavior in notched specimens of INCONEL 718

Notches were machined in specimens of INCONEL 718 by a broaching process, where differing broaching runs led to differing extents of subsurface deformation and surface roughness. Fatigue tests were carried out at 600°C with a trapezoidal loading waveform at 0.25 Hz. The broaching process that led to the more severe subsurface deformation (but lower surface roughness) showed the worst fatigue performance. Analysis of total strain amplitude in the notch root with the aid of an elasto-plastic finite-element (FE) model showed that the work hardening related to the subsurface deformation caused by the different broaching can account for the difference in fatigue lives. Differences in initiation and growth behavior were seen for the two broached finishes as well as for broached and subsequently polished samples. These differences are discussed in terms of a change in crack growth initiation and growth mechanisms due to the presence of the work-hardened layer

Detecting Anomalies in Controlled Drug Prescription Data Using Probabilistic Models

Abstract. Opioid analgesic drugs are widely used in pain management and substance dependence treatment. However, these drugs have high potential for misuse and subsequent harm. As a result, their prescribing is monitored and controlled. In Queensland, Australia, the Medicines Regulation and Quality Unit within the state health system maintains a database of prescribing events and uses this data to identify anoma-lies and provide subsequent support for patients and prescribers. In this study, we consider this task as an unsupervised anomaly detection prob-lem. We use probability density estimation models to describe the dis-tribution of the data over a number of key attributes and use the model to identify anomalies as points with low estimated probability. The re-sults are validated against cases identified by healthcare domain experts. There was strong agreement between cases identified by the models and expert clinical assessment

A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions

BACKGROUND:Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services. METHODS:This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments. RESULTS:Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.9 to - 0.2, p = 0.006); (3) 'Meeting the adult team before transfer', example associations with Participation (arranging services and aids) (odds ratio 5.2, 95% CI 2.1-12.8, p < 0.001) and with Autonomy in Appointments (average 1.7 points higher, 95% CI 0.8-2.6, p < 0.001). There was slightly less recruitment of participants from areas with greater socioeconomic deprivation, though not with respect to family composition. CONCLUSIONS:Three features of transitional care were associated with improved outcomes. Results are likely to be generalisable because participants had three very different conditions, attending services at many UK sites. Results are relevant for clinicians as well as for commissioners and managers of health services. The challenge of introducing these three features across child and adult healthcare services, and the effects of doing so, should be assessed.A. Colver, H. McConachie, A. Le Couteur, G. Dovey-Pearce, K. D. Mann, J. E. McDonagh ... et al. (On behalf of the Transition Collaborative Group