Checkpoint inhibition of origin firing prevents DNA topological stress.

A universal feature of DNA damage and replication stress in eukaryotes is the activation of a checkpoint-kinase response. In S-phase, the checkpoint inhibits replication initiation, yet the function of this global block to origin firing remains unknown. To establish the physiological roles of this arm of the checkpoint, we analyzed separation of function mutants in the budding yeast Saccharomyces cerevisiae that allow global origin firing upon replication stress, despite an otherwise normal checkpoint response. Using genetic screens, we show that lack of the checkpoint-block to origin firing results in a dependence on pathways required for the resolution of topological problems. Failure to inhibit replication initiation indeed causes increased DNA catenation, resulting in DNA damage and chromosome loss. We further show that such topological stress is not only a consequence of a failed checkpoint response but also occurs in an unperturbed S-phase when too many origins fire simultaneously. Together we reveal that the role of limiting the number of replication initiation events is to prevent DNA topological problems, which may be relevant for the treatment of cancer with both topoisomerase and checkpoint inhibitors.

Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

The state of costing research for HIV interventions in sub-Saharan Africa.

The past decade has seen a growing emphasis on the production of high-quality costing data to improve the efficiency and cost-effectiveness of global health interventions. The need for such data is especially important for decision making and priority setting across HIV services from prevention and testing to treatment and care. To help address this critical need, the Global Health Cost Consortium was created in 2016, in part to conduct a systematic search and screening of the costing literature for HIV and TB interventions in low- and middle-income countries (LMIC). The purpose of this portion of the remit was to compile, standardise, and make publicly available published cost data (peer-reviewed and gray) for public use. We limit our analysis to a review of the quantity and characteristics of published cost data from HIV interventions in sub-Saharan Africa. First, we document the production of cost data over 25 years, including density over time, geography, publication venue, authorship and type of intervention. Second, we explore key methods and reporting for characteristics including urbanicity, platform type, ownership and scale. Although the volume of HIV costing data has increased substantially on the continent, cost reporting is lacking across several dimensions. We find a dearth of cost estimates from HIV interventions in west Africa, as well as inconsistent reporting of key dimensions of cost including platform type, ownership and urbanicity. Further, we find clear evidence of a need for renewed focus on the consistent reporting of scale by authors of costing and cost-effectiveness analyses.

Developing the Global Health Cost Consortium Unit Cost Study Repository for HIV and TB: methodology and lessons learned.

Consistently defined, accurate, and easily accessible cost data are a valuable resource to inform efficiency analyses, budget preparation, and sustainability planning in global health. The Global Health Cost Consortium (GHCC) designed the Unit Cost Study Repository (UCSR) to be a resource for standardised HIV and TB intervention cost data displayed by key characteristics such as intervention type, country, and target population. To develop the UCSR, the GHCC defined a typology of interventions for each disease; aligned interventions according to the standardised principles, methods, and cost and activity categories from the GHCC Reference Case for Estimating the Costs of Global Health Services and Interventions; completed a systematic literature review; conducted extensive data extraction; performed quality assurance; grappled with complex methodological issues such as the proper approach to the inflation and conversion of costs; developed and implemented a study quality rating system; and designed a web-based user interface that flexibly displays large amounts of data in a user-friendly way. Key lessons learned from the extraction process include the importance of assessing the multiple uses of extracted data; the critical role of standardising definitions (particularly units of measurement); using appropriate classifications of interventions and components of costs; the efficiency derived from programming data checks; and the necessity of extraction quality monitoring by senior analysts. For the web interface, lessons were: understanding the target audiences, including consulting them regarding critical characteristics; designing the display of data in "levels"; and incorporating alert and unique trait descriptions to further clarify differences in the data.

Parents as Teachers Health Literacy Demonstration project: integrating an empowerment model of health literacy promotion into home-based parent education.

The Parents as Teachers (PAT) Health Literacy Demonstration project assessed the impact of integrating data-driven reflective practices into the PAT home visitation model to promote maternal health literacy. PAT is a federally approved Maternal, Infant, Early Childhood Home Visiting program with the goal of promoting school readiness and healthy child development. This 2-year demonstration project used an open-cohort longitudinal design to promote parents' interactive and reflective skills, enhance health education, and provide direct assistance to personalize and act on information by integrating an empowerment paradigm into PAT's parent education model. Eight parent educators used the Life Skills Progression instrument to tailor the intervention to each of 103 parent-child dyads. Repeated-measures analysis of variance, paired t tests, and logistic regression combined with qualitative data demonstrated that mothers achieved overall significant improvements in health literacy, and that home visitors are important catalysts for these improvements. These findings support the use of an empowerment model of health education, skill building, and direct information support to enable parents to better manage personal and child health and health care.

Visualization and analytics tools for infectious disease epidemiology: a systematic review.

BACKGROUND: A myriad of new tools and algorithms have been developed to help public health professionals analyze and visualize the complex data used in infectious disease control. To better understand approaches to meet these users' information needs, we conducted a systematic literature review focused on the landscape of infectious disease visualization tools for public health professionals, with a special emphasis on geographic information systems (GIS), molecular epidemiology, and social network analysis. The objectives of this review are to: (1) identify public health user needs and preferences for infectious disease information visualization tools; (2) identify existing infectious disease information visualization tools and characterize their architecture and features; (3) identify commonalities among approaches applied to different data types; and (4) describe tool usability evaluation efforts and barriers to the adoption of such tools. METHODS: We identified articles published in English from January 1, 1980 to June 30, 2013 from five bibliographic databases. Articles with a primary focus on infectious disease visualization tools, needs of public health users, or usability of information visualizations were included in the review. RESULTS: A total of 88 articles met our inclusion criteria. Users were found to have diverse needs, preferences and uses for infectious disease visualization tools, and the existing tools are correspondingly diverse. The architecture of the tools was inconsistently described, and few tools in the review discussed the incorporation of usability studies or plans for dissemination. Many studies identified concerns regarding data sharing, confidentiality and quality. Existing tools offer a range of features and functions that allow users to explore, analyze, and visualize their data, but the tools are often for siloed applications. Commonly cited barriers to widespread adoption included lack of organizational support, access issues, and misconceptions about tool use. DISCUSSION AND CONCLUSION: As the volume and complexity of infectious disease data increases, public health professionals must synthesize highly disparate data to facilitate communication with the public and inform decisions regarding measures to protect the public's health. Our review identified several themes: consideration of users' needs, preferences, and computer literacy; integration of tools into routine workflow; complications associated with understanding and use of visualizations; and the role of user trust and organizational support in the adoption of these tools. Interoperability also emerged as a prominent theme, highlighting challenges associated with the increasingly collaborative and interdisciplinary nature of infectious disease control and prevention. Future work should address methods for representing uncertainty and missing data to avoid misleading users as well as strategies to minimize cognitive overload.

Distinct anal microbiome is correlated with anal cancer precursors in men who have sex with men living with HIV.

OBJECTIVES: Anal cancer risk is elevated in men who have sex with men living with HIV (MSMLWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMLWH. DESIGN: Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMLWH and cross-sectional comparison of the anal microbiome of MSMLWH with anal HSIL with the anal microbiome of MSMLWH without anal HSIL. METHODS: Sterile swabs were used to sample the anus of MSMLWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity and differential abundance analysis were used to compare samples. RESULTS: 166 anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMLWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMLWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMLWH/hr-HPV/HSIL. CONCLUSIONS: The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL.

Serving limited English proficient callers: a survey of 9-1-1 police telecommunicators.

INTRODUCTION: The emergency telephone number 9-1-1 serves as a lifeline to the public during emergencies, and first responders rely on information gathered by 9-1-1 telecommunicators who speak with callers. Timely, accurate information from the telecommunicators is essential for providing appropriate care on scene. Language barriers can hamper these efforts and result in less efficient information exchange. Although 9-1-1 telecommunicators may access over-the-phone interpreter (OPI) services to facilitate communication, managing three-way communication during an emergency is challenging. Problem There is little published on the relationship between limited English proficient (LEP) callers and 9-1-1 police telecommunicators, and the role of OPI services during these calls. Further, little is known about effective strategies to manage such calls. METHODS: In King County, Washington, 9-1-1 police telecommunicators were surveyed about their experiences handling LEP calls and managing three-way communication with OPI services. The survey contained 13 multiple-choice and three open-response questions addressing communication strategies, challenges with LEP callers, and three-way communication with OPI services. Goodman-Kruskal Gamma and chi-square tests were conducted with OPI use as the dependent variable. Additional analyses were conducted using stress levels as the dependent variable. RESULTS: Of 123 respondents, 69 (56.5%) 9-1-1 telecommunicators reported utilizing OPI services at least 75% of the time when receiving a call from an LEP caller. Further, 35 (28.7%) of these telecommunicators reported calls with LEP individuals as more stressful than calls with fluent English speakers. Dispatcher stress level during LEP calls compared with stress during calls with fluent English speakers was positively associated with use of OPI services (P < .01). Further, stress level was also positively associated with telecommunicator difficulties in assessing the situation with respect to officer safety (P < .01). Sixty-three (58.3%) of the telecommunicators described difficulties assessing the situation to determine the appropriate response as the biggest challenge with LEP callers. Additionally, 62 (53%) identified knowing their location in English as information LEP callers need to know prior to calling 9-1-1. CONCLUSION: These results highlight intervention opportunities for both 9-1-1 telecommunicators and LEP communities. Together, interventions such as working with LEP communities to educate them on best communication practices during 9-1-1 calls, and with 9-1-1 telecommunicators to help them manage three-way communication and reduce stress associated with concern for officer safety may improve emergency communication during 9-1-1 calls.

Differential impact of test performance characteristics on burden-to-benefit tradeoffs for blood-based colorectal cancer screening: A microsimulation analysis.

OBJECTIVES: To inform the development and evaluation of new blood-based colorectal cancer (CRC) screening tests satisfying minimum United States (US) coverage criteria, we estimated the impact of the different test performance characteristics on long-term testing benefits and burdens. METHODS: A novel CRC-Microsimulation of Adenoma Progression and Screening (CRC-MAPS) model was developed, validated, then used to assess different screening tests for CRC. We compared multiple, hypothetical blood-based CRC screening tests satisfying minimum coverage criteria of 74% CRC sensitivity and 90% specificity, to measure how changes in a test's CRC sensitivity, specificity, and adenoma sensitivity (sizes 1-5 mm, 6-9 mm, ≥10 mm) affect total number of colonoscopies (COL), CRC incidence reduction (IR), CRC mortality reduction (MR), and burden-to-benefit ratios (incremental COLs per percentage-point increase in IR or MR). RESULTS: A blood test meeting minimum US coverage criteria for performance characteristics resulted in 1576 lifetime COLs per 1000 individuals, 46.7% IR and 59.2% MR compared to no screening. Tests with increased CRC sensitivity of 99% ( + 25%) vs. increased ≥10 mm adenoma sensitivity of 13.6% ( + 3.6%) both yielded the same MR, 62.7%. Test benefits improved the most with increases in all-size adenoma sensitivity, then size-specific adenoma sensitivities, then specificity and CRC sensitivity, while increases in specificity or ≥10 mm adenoma sensitivity resulted in the most favorable burden-to-benefit tradeoffs (ratios <11.5). CONCLUSIONS: Burden-to-benefit ratios for blood-based CRC screening tests differ by performance characteristic, with the most favorable tradeoffs resulting from improvements in specificity and ≥10 mm adenoma sensitivity.

Interrogating intervention delivery and participants' emotional states to improve engagement and implementation: A realist informed multiple case study evaluation of Engager.

BACKGROUND: 'Engager' is an innovative 'through-the-gate' complex care intervention for male prison-leavers with common mental health problems. In parallel to the randomised-controlled trial of Engager (Trial registration number: ISRCTN11707331), a set of process evaluation analyses were undertaken. This paper reports on the depth multiple case study analysis part of the process evaluation, exploring how a sub-sample of prison-leavers engaged and responded to the intervention offer of one-to-one support during their re-integration into the community. METHODS: To understand intervention delivery and what response it elicited in individuals, we used a realist-informed qualitative multiple 'case' studies approach. We scrutinised how intervention component delivery lead to outcomes by examining underlying causal pathways or 'mechanisms' that promoted or hindered progress towards personal outcomes. 'Cases' (n = 24) were prison-leavers from the intervention arm of the trial. We collected practitioner activity logs and conducted semi-structured interviews with prison-leavers and Engager/other service practitioners. We mapped data for each case against the intervention logic model and then used Bhaskar's (2016) 'DREIC' analytic process to categorise cases according to extent of intervention delivery, outcomes evidenced, and contributing factors behind engagement or disengagement and progress achieved. RESULTS: There were variations in the dose and session focus of the intervention delivery, and how different participants responded. Participants sustaining long-term engagement and sustained change reached a state of 'crises but coping'. We found evidence that several components of the intervention were key to achieving this: trusting relationships, therapeutic work delivered well and over time; and an in-depth shared understanding of needs, concerns, and goals between the practitioner and participants. Those who disengaged were in one of the following states: 'Crises and chaos', 'Resigned acceptance', 'Honeymoon' or 'Wilful withdrawal'. CONCLUSIONS: We demonstrate that the 'implementability' of an intervention can be explained by examining the delivery of core intervention components in relation to the responses elicited in the participants. Core delivery mechanisms often had to be 'triggered' numerous times to produce sustained change. The improvements achieved, sustained, and valued by participants were not always reflected in the quantitative measures recorded in the RCT. The compatibility between the practitioner, participant and setting were continually at risk of being undermined by implementation failure as well as changing external circumstances and participants' own weaknesses. TRIAL REGISTRATION NUMBER: ISRCTN11707331, Wales Research Ethics Committee, Registered 02-04-2016-Retrospectively registered https://doi.org/10.1186/ISRCTN11707331.

Gut microbiome composition and risk factors in a large cross-sectional IBS cohort.

Objective: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is difficult to diagnose and treat due to its inherent heterogeneity and unclear aetiology. Although there is evidence suggesting the importance of the microbiome in IBS, this association remains poorly defined. In the current study, we aimed to characterise a large cross-sectional cohort of patients with self-reported IBS in terms of microbiome composition, demographics, and risk factors. Design: Individuals who had previously submitted a stool sample for 16S microbiome sequencing were sent a comprehensive survey regarding IBS diagnosis, demographics, health history, comorbidities, family history, and symptoms. Log ratio-transformed abundances of microbial taxa were compared between individuals reporting a diagnosis of IBS without any comorbidities and individuals reporting no health conditions. Univariable testing was followed by a multivariable logistic regression model controlling for relevant confounders. Results: Out of 6386 respondents, 1692 reported a diagnosis of IBS without comorbidities and 1124 reported no health conditions. We identified 3 phyla, 15 genera, and 19 species as significantly associated with IBS after adjustment for confounding factors. Demographic risk factors include a family history of gut disorders and reported use of antibiotics in the last year. Conclusion: The results of this study confirm important IBS risk factors in a large cohort and support a connection for microbiome compositional changes in IBS pathogenesis. The results also suggest clinical relevance in monitoring and investigating the microbiome in patients with IBS. Further, the exploratory models described here provide a foundation for future studies.

An evaluation of the Fishing For Litter (FFL) scheme in the UK in terms of attitudes, behavior, barriers and opportunities.

Marine litter is a global, persistent, and increasing threat to the oceans, and numerous initiatives aim to address this challenge. Fishing For Litter (FFL) is a voluntary clean-up scheme, where litter is collected as part of routine fishing operations. We surveyed fishers (n = 97) and stakeholders (n = 22) in the UK to investigate perceptions of FFL, its strengths and weaknesses, and potential co-benefits of the scheme. Fishers reported being aware of and concerned about the negative impacts of litter. Overall, FFL was evaluated very positively (7.85/10). In addition, FFL fishers reported less environmentally harmful waste management behaviors both out at sea and in other contexts than did non-FFL fishers. Fishers and stakeholders listed strengths and weaknesses of the scheme and made suggestions for future changes. As well as directly helping to remove litter, this paper demonstrates that clean-up schemes can make a contribution to addressing the underlying causes of marine pollution.

Pilot randomised controlled trial of the ENGAGER collaborative care intervention for prisoners with common mental health problems, near to and after release.

BACKGROUND: Rates of common mental health problems are much higher in prison populations, but access to primary care mental health support falls short of community equivalence. Discontinuity of care on release is the norm and is further complicated by substance use and a range of social problems, e.g. homelessness. To address these problems, we worked with criminal justice, third sector social inclusion services, health services and people with lived experiences (peer researchers), to develop a complex collaborative care intervention aimed at supporting men with common mental health problems near to and following release from prison. This paper describes an external pilot trial to test the feasibility of a full randomised controlled trial. METHODS: Eligible individuals with 4 to 16 weeks left to serve were screened to assess for common mental health problems. Participants were then randomised at a ratio of 2:1 allocation to ENGAGER plus standard care (intervention) or standard care alone (treatment as usual). Participants were followed up at 1 and 3 months' post release. Success criteria for this pilot trial were to meet the recruitment target sample size of 60 participants, to follow up at least 50% of participants at 3 months' post release from prison, and to deliver the ENGAGER intervention. Estimates of recruitment and retention rates and 95% confidence intervals (CIs) are reported. Descriptive analyses included summaries (percentages or means) for participant demographics, and baseline characteristics are reported. RESULTS: Recruitment target was met with 60 participants randomised in 9 months. The average retention rates were 73% at 1 month [95% CI 61 to 83] and 47% at 3 months follow-up [95% CI 35 to 59]. Ninety percent of participants allocated to the intervention successfully engaged with a practitioner before release and 70% engaged following release. CONCLUSIONS: This pilot confirms the feasibility of conducting a randomised trial for prison leavers with common mental health problems. Based on this pilot study and some minor changes to the trial design and intervention, a full two-centre randomised trial assessing the clinical and cost-effectiveness of the ENGAGER intervention is currently underway.

Evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: study protocol for a randomised controlled trial.

INTRODUCTION: The 'Engager' programme is a 'through-the-gate' intervention designed to support prisoners with common mental health problems as they transition from prison back into the community. The trial will evaluate the clinical and cost-effectiveness of the Engager intervention. METHODS AND ANALYSIS: The study is a parallel two-group randomised controlled trial with 1:1 individual allocation to either: (a) the Engager intervention plus standard care (intervention group) or (b) standard care alone (control group) across two investigation centres (South West and North West of England). Two hundred and eighty prisoners meeting eligibility criteria will take part. Engager is a person-centred complex intervention delivered by practitioners and aimed at addressing offenders' mental health and social care needs. It comprises one-to-one support for participants prior to release from prison and for up to 20 weeks postrelease. The primary outcome is change in psychological distress measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary outcomes include: assessment of subjective met/unmet need, drug and alcohol use, health-related quality of life and well-being-related quality of life measured at 3, 6 and 12 months postrelease; change in objective social domains, drug and alcohol dependence, service utilisation and perceived helpfulness of services and change in psychological constructs related to desistence at 6 and 12 months postrelease; and recidivism at 12 months postrelease. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action and look for unintended consequences. An economic evaluation will estimate the cost-effectiveness. ETHICS AND DISSEMINATION: This study has been approved by the Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender Management Service (ref: 2015-283). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations. TRIAL REGISTRATION NUMBER: ISRCTN11707331; Pre-results.

Data-Driven Maternal Health Literacy Promotion and a Postscript on Its Implications.

Scientific discovery and global health policy are moving health literacy promotion and maternal-child health from the fringes of research and public health to the forefront of healthcare reform [1]. In 2011 the United Nations General Assembly adopted the Shanghai Declaration [2]. The Declaration highlights new understanding of the origins of health and disease in early development. It calls on all nations to apply this knowledge to reduce the burdens of chronic disease and related disparities worldwide. The Declaration recommends a specific intervention strategy: promote health literacy across the life course, particularly in parents and children, and empower women. This chapter explores findings and implications of the Life Skills Progression Maternal Health Literacy studies. These LSP-MHL studies evaluated implementations of an intervention designed to promote health literacy in parents and empower women in the U.S. First, the chapter reports findings of the most recent of five published LSP-MHL studies with discussion of its implications for future work in this line of inquiry. A postscript highlights two of many implications of the LSP-MHL intervention studies for health literacy research in the third era of modern healthcare.

Whole-system approaches to improving the health and wellbeing of healthcare workers: A systematic review.

BACKGROUND: Healthcare professionals throughout the developed world report higher levels of sickness absence, dissatisfaction, distress, and "burnout" at work than staff in other sectors. There is a growing call for the 'triple aim' of healthcare delivery (improving patient experience and outcomes and reducing costs; to include a fourth aim: improving healthcare staff experience of healthcare delivery. A systematic review commissioned by the United Kingdom's (UK) Department of Health reviewed a large number of international healthy workplace interventions and recommended five whole-system changes to improve healthcare staff health and wellbeing: identification and response to local need, engagement of staff at all levels, and the involvement, visible leadership from, and up-skilling of, management and board-level staff. OBJECTIVES: This systematic review aims to identify whole-system healthy workplace interventions in healthcare settings that incorporate (combinations of) these recommendations and determine whether they improve staff health and wellbeing. METHODS: A comprehensive and systematic search of medical, education, exercise science, and social science databases was undertaken. Studies were included if they reported the results of interventions that included all healthcare staff within a healthcare setting (e.g. whole hospital; whole unit, e.g. ward) in collective activities to improve physical or mental health or promote healthy behaviours. RESULTS: Eleven studies were identified which incorporated at least one of the whole-system recommendations. Interventions that incorporated recommendations to address local need and engage the whole workforce fell in to four broad types: 1) pre-determined (one-size-fits-all) and no choice of activities (two studies); or 2) pre-determined and some choice of activities (one study); 3) A wide choice of a range of activities and some adaptation to local needs (five studies); or, 3) a participatory approach to creating programmes responsive and adaptive to local staff needs that have extensive choice of activities to participate in (three studies). Only five of the interventions included substantial involvement and engagement of leadership and efforts aimed at up-skilling the leadership of staff to support staff health and wellbeing. Incorporation of more of the recommendations did not appear to be related to effectiveness. The heterogeneity of study designs, populations and outcomes excluded a meta-analysis. All studies were deemed by their authors to be at least partly effective. Two studies reported statistically significant improvement in objectively measured physical health (BMI) and eight in subjective mental health. Six studies reported statistically significant positive changes in subjectively assessed health behaviours. CONCLUSIONS: This systematic review identified 11 studies which incorporate at least one of the Boorman recommendations and provides evidence that whole-system healthy workplace interventions can improve health and wellbeing and promote healthier behaviours in healthcare staff.

Evidence for proactive interference in the focus of attention of working memory.

Proactive interference (PI) occurs when an earlier item interferes with memory for a newer item. Whereas some researchers (e.g., Surprenant & Neath, 2009a) argue that PI can be observed in all memory systems, some multiple systems theorists (e.g., Cowan, 1999) propose that items in the focus of attention of working memory are immune to PI. Two experiments tested whether PI occurs when the to-be-remembered items are assumed, by multiple-systems theorists, to be held in the focus of attention. In each experiment, subjects saw four trials in a row with the same type of to-be-remembered items, followed by four trials in a row with a different type of material. On each trial, only 3 stimuli were shown, which is below the capacity limit of the focus of attention, and subjects were asked if a probe item was one of those 3 items seen. In both experiments, response time increased from Trial 1 to Trial 4, suggesting that items from the earlier trials interfered with memory on the later trials. In addition, release from PI was shown in that response times decreased with a change of materials. The results replicate those first reported by Hanley and Scheirer (1975), and pose a problem for theorists who argue that parts of short-term memory are immune to PI.

Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy.

OBJECTIVES: To report our experience with intraoperative frozen section (IFS) analysis in patients who are potential candidates for nerve-sparing surgery. Potency can be maintained in select patients who undergo radical prostatectomy using a nerve-sparing approach. However, extracapsular disease extension in the area of the neurovascular bundles may compromise adequate surgical margins in some patients undergoing such surgery. METHODS: We reviewed the pathologic results from 101 patients who underwent either unilateral or bilateral nerve-sparing radical prostatectomy in whom IFS analysis was performed. The clinical disease stage was T1 in 20 patients and T2 in 81 patients. The mean serum prostate-specific antigen level before surgery was 7.2 ng/mL. Of the 101 patients, 62, 28, and 11 had a biopsy Gleason score of 2 to 6, 7, and 8 to 10, respectively. IFS analysis was performed on the surgical margin thought to be at risk of tumor involvement as determined by the results of systematic prostate biopsy, transrectal ultrasonography, or intraoperative inspection. If the frozen section was positive, additional tissue, including the neurovascular bundle, was subsequently removed to establish clear surgical margins. IFS results were compared with those on the final, permanent tissue section, as well as with the status of the additionally resected tissue. RESULTS: The IFS results were identical to those obtained on the final, permanent section in 92 (91%) of the 101 cases. The IFS results showed positive margins in 15 (15%) of 101 patients. Of these cases, 11 demonstrated positive margins on the final permanent sections. Of the 86 patients with negative frozen section diagnosis, 5 had positive surgical margins on permanent sections at the site of the IFS. The positive and negative predictive value for the IFS technique was 73% and 94%, respectively. Of the 15 patients with positive IFS, 12 (80%) had no evidence of tumor in the additionally resected tissue. Prostate-specific antigen recurrence was noted in 7% of the study population. The risk of recurrence in patients with either positive or negative IFS findings was similar. CONCLUSIONS: IFS at the time of radical prostatectomy can reliably predict the final surgical margin status in most carefully selected high-risk patients when there are concerns about the margin status.