Factors that influence psychiatric trainees’ choice of higher training specialty: mixed-methods study

Aims and method Factors influencing trainees’ decisions about choosing and remaining in higher training subspecialties have not been widely researched. We administered telephone questionnaires to higher specialist trainees in the north-east of England to ascertain what influences these decisions. Thematic analysis was employed to develop overall constructs. Results Twenty-seven trainees were interviewed, resulting in six overall constructs. These were: supervisory experiences; perceived work–life balance; career prospects; training and working environments; interest in the chosen subspecialty; and previous experience within the chosen subspecialty. Most trainees interviewed felt they had made the right specialty choice. Clinical implications This study demonstrates the particular importance of exposure to a specialty and perceptions of the supervisory experience in determining trainees’ choices of, and decisions to remain in, a particular psychiatric specialty. Factors highlighted in this study must inform training, recruitment and workforce planning in order to bolster the recruitment and retention of trainees into higher specialty training

Author Correction:C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption

Correction to: Nature Communications https://doi.org/10.1038/s41467-023-40779-9, published online 17 August 2023

Working with wood in rivers in the Western United States

Recognition of the important physical and ecological roles played by large wood in channels and on floodplains has grown substantially during recent decades. Although large wood continues to be routinely removed from many river corridors worldwide, the practice of wood reintroduction has spread across the United States, the United Kingdom and western Europe, Australia, and New Zealand. The state-of-science regarding working with wood in rivers was discussed during a workshop held in Colorado, USA, in September 2022 with 40 participants who are scientists and practitioners from across the USA, UK, Europe, and Japan. The objectives of this paper are to present the findings from the workshop; summarize two case studies of wood in river restoration in the western United States; and provide suggestions for advancing the practice of wood in river management. We summarize the workshop results based on participant judgements and recommendations with respect to: (i) limitations and key barriers to using wood, which reflect perceptions and practicalities; (ii) gaps in the use of large wood in river management; (iii) scenarios in which wood is generally used effectively; and (iv) scenarios in which wood is generally not used effectively. The case studies illustrate the importance of the local geomorphic context, the configuration complexity of the wood, and the potential for modification of river corridor morphology to enhance desired benefits. Moving forward, we stress the importance of collaboration across disciplines and across communities of research scientists, practitioners, regulators, and potential stakeholders; accounting for stakeholder perceptions of the use of large wood; and increasing non-scientist access to the latest state-of-science knowledge

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis:a randomised, double-blind, placebo-controlled, phase 2b trial

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings: Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation: Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials

Building consensus in strategic decision-making : system dynamics as a group support system

Contains fulltext : 28724.pdf (publisher's version ) (Open Access)System dynamics was originally founded as a method for modeling and simulating the behavior of industrial systems. In recent years it is increasingly employed as a Group Support System for strategic decision-making groups. The model is constructed in direct interaction with a management team, and the procedure is generally referred to as group model-building. The model can be conceptual (qualitative) or a full-blown (quantitative) computer simulation model. In this article, a case is described in which a qualitative system dynamics model was built to support strategic decision making in a Dutch government agency. Since people from different departments held strongly opposite viewpoints on the strategy, the agency had discussed its strategic problem for more than a year, but was obviously not able to reach consensus. The application of group model-building was successful in integrating opposite points of view, as well as in fostering consensus and creating commitment. The purpose of the article is twofold: first, to illustrate the process of group model-building with system dynamics; second, to evaluate why it was successful. Evaluation results reveal the importance of both systemic thinking through model-building and the role of the facilitator in catalyzing the strategic decision-making process

Reinterpreting 'generic structure': evolution, application and limitations of a concept

This paper traces the evolution of the generic structure concept in system dynamics and discusses the different practical uses to which they have been put. A review of previous work leads to the identification of three different views of what a generic structure is and, hence, what transferability means. These different views are distinguishable in application as well as in theory. Examination of these interpretations shows that the assumptions behind them are quite distinct. From this analysis it is argued that it is no longer useful to treat generic structure as a single concept since the unity it implies is only superficial. The conclusion is that the concept needs unbundling so that different assumptions about transferability of structure can be made explicit, and the role of generic structures as generalisable theories of dynamic behaviour in system dynamics theory and practice can be debated and clarified more effectively

C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption

Abstract While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide screen for genes that are synthetic lethal with PARP1/2 gene disruption and identified C16orf72/HAPSTR1/TAPR1 as a novel modulator of replication-associated R-loops. C16orf72 is critical to facilitate replication fork restart, suppress DNA damage and maintain genome stability in response to replication stress. Importantly, C16orf72 and PARP1/2 function in parallel pathways to suppress DNA:RNA hybrids that accumulate at stalled replication forks. Mechanistically, this is achieved through an interaction of C16orf72 with BRCA1 and the RNA/DNA helicase Senataxin to facilitate their recruitment to RNA:DNA hybrids and confer resistance to PARP inhibitors. Together, this identifies a C16orf72/Senataxin/BRCA1-dependent pathway to suppress replication-associated R-loop accumulation, maintain genome stability and confer resistance to PARP inhibitors