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

Long-Term Functionality of Rural Water Services in Developing Countries: A System Dynamics Approach to Understanding the Dynamic Interaction of Causal Factors

Research has shown that sustainability of rural water infrastructure in developing countries is largely affected by the dynamic and systemic interactions of technical, social, financial, institutional, and environmental factors that can lead to premature water system failure. This research employs systems dynamic modeling, which uses feedback mechanisms to understand how these factors interact dynamically to influence long-term rural water system functionality. To do this, the research first identified and aggregated key factors from literature, then asked water sector experts to indicate the polarity and strength between factors through Delphi and cross impact survey questionnaires, and finally used system dynamics modeling to identify and prioritize feedback mechanisms. The resulting model identified 101 feedback mechanisms that were dominated primarily by three and four-factor loops that contained some combination of the factors: Water System Functionality, Community, Financial, Government, Management, and Technology. These feedback mechanisms were then scored and prioritized, with the most dominant feedback mechanism identified as Water System Functionality – Community – Finance – Management. This research offers insight into the dynamic interaction of factors impacting sustainability of rural water infrastructure through the identification of these feedback mechanisms and makes a compelling case for future research to longitudinally investigate the interaction of these factors in various contexts

Impact of primary health care providers’ initial role security and therapeutic commitment on implementing brief interventions in managing risky alcohol consumption: a cluster randomised factorial trial

Background: Brief interventions in primary healthcare to detect and intervene in risky alcohol consumption are cost-effective in reducing drinking problems, but poorly implemented in routine care. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation.Methods: In a cluster randomised factorial trial 120 Primary Healthcare Units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined. To explore the impact of initial role security and therapeutic commitment on implementing brief interventions, we performed multilevel linear regression analyses adapted to the factorial design. Results: Data from 746 providers of 120 PHCUs were included in the analyses. Baseline role security and therapeutic commitment were found not to influence implementation of brief interventions. Furthermore there were no significant interactions between these characteristics and allocated groups. Conclusions: The extent to which providers’ managed to change their brief intervention proportions when submitted to different implementation strategies was not determined by their initial attitudes towards alcohol problems. In future research more attention is needed for the causal relation between these parameters, as it can inform us whether to focus on these or not in implementation trajectories

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

A National Survey of Assertive Outreach Treatment Services for People Who Frequently Attend Hospital due to Alcohol-Related Reasons in England

Aims To characterize England’s alcohol assertive outreach treatment (AAOT) services for people who frequently attend hospital due to alcohol-related reasons according to their concordance with six core AAOT components. Methods A cross-sectional national survey using structured telephone interviews with health professionals examining 6 essential AAOT components. High-level AAOT services were those that delivered 5 or more components, mid-level 3 to 4 components, low-level AAOT services 2 or less. Results The analysis included 37 services that were classified according to their concordance with the 6 AAOT components. Six were identified as high-level AAOT services, 13 as mid-level AAOT services and 18 as low-level services. Extended support covering housing, mental and physical health over and above alcohol consumption was the most commonly delivered AAOT component provided. Having a multidisciplinary team was the least observed component, delivered in 33% high-level AAOT services and in 15% mid-level AAOT services. None of the low-level AAOT services had a multidisciplinary team. Conclusions Access to AAOT services developed to support high-cost and high-needs frequent hospital attenders varies across the nation. Further research, service evaluation and AAOT implementation should focus on essential AAOT components rather than self-defined labels of AAOT. Short summary The study investigated alcohol assertive outreach treatment (AAOT) services in England. The study found variability in service provision across AAOT services when measured against six essential AAOT components. Improvement of AAOT in England’s hospitals should focus on the implementation of essential AAOT components.</p

Identifying the gap between need and intervention for alcohol use disorders in Europe

A literature review of existing research on the prevalence of alcohol use disorders (AUDs) and availability of alcohol interventions in Europe was conducted. The review also explored what is known about the gap between need and provision of alcohol interventions in Europe. Methods The review search strategy included: (i) descriptive studies of alcohol intervention systems in Europe; (ii) studies of alcohol service provision in Europe; and (iii) studies of prevalence of AUD and alcohol needs assessment in Europe. Results Europe has a relatively high level of alcohol consumption and the resulting disabilities are the highest in the world. Most research on implementation of alcohol interventions in Europe has been restricted to screening and brief interventions. Alcohol needs assessment methodology has been developed but has not been applied in comparative studies across countries in Europe. Conclusions This review points to key gaps in knowledge related to alcohol interventions in Europe. There is a lack of comparative data on variations in alcohol treatment systems across European countries and there is also a lack of comparative data on the prevalence of alcohol use disorders across European countries and the relative gap between need and access to treatment. The forthcoming Alcohol Measures for Public Health Research Alliance (AMPHORA) research projectwork package on ‘Early identification and treatment’ aims to address these gaps

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

Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C

Introduction and objective: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. Method: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12‐week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT‐C; the proportion of screen‐negative patients given advice, and the proportion of screen‐positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet‐based counselling. Results: Thirty‐two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen‐negative patients were falsely classified. At baseline, 27% of screen‐negative patients were given advice, and 22.5% screen‐positive patients were not given advice. These proportions halved during the 12‐week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen‐positive patients not given advice (OR = 0.56; 95% CI, 0.31‐0.99; P < .05). Conclusion: Although the use of AUDIT‐C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives