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Abstract Background The purpose of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) Program, a Cancer Moonshot℠ Initiative, is to support research to build the evidence base on multilevel interventions that increase rates of colorectal cancer screening, follow-up, and referral to care to address disparities in colorectal cancer screening. The National Cancer Institute funded eight Research Projects to implement multilevel interventions to improve colorectal cancer screening among communities who traditionally have been medically underserved. To analyze the impact of ACCSIS across Research Projects, the consortium developed a set of common data elements. The purpose of this paper is to describe the process of developing the common data elements to facilitate analysis of ACCSIS data as well as support and inform implementation science research studies. Methods The ACCSIS Data, Design, and Analysis Work Group was tasked with designing common data elements through a review of existing data collection instruments, examination of data elements proposed by the ACCSIS Research Projects, and deliberations on the data required to compare across the Research Projects. ACCSIS Consortium members drafted, revised, and finalized a common data elements document consisting of variables to collect and surveys to administer to evaluate ACCSIS implementation activities and outcomes in a standardized manner across the Research Projects. Results The ACCSIS Consortium decided to collect the following categories of common data elements: characteristics across multiple levels of the multicomponent interventions, implementation climate, and determinants; interventions and strategies; implementation outcome constructs and definitions; colorectal cancer screening episodes (screening, diagnostic testing follow-up, cancer detection, and cancer treatment); and cost measures. To assess implementation climate, the consortium prioritized constructs from five domains of the Consolidated Framework for Implementation Research. Conclusions The ACCSIS common data elements offer a set of harmonization data for future implementation efforts. The consortium is conducting a systematic assessment using both quantitative and qualitative approaches to assess data quality and approaches to improve and sustain data collection. Lessons learned from these ongoing activities will offer additional insights to tailor the ACCSIS common data elements and support efforts to increase colorectal cancer screening for populations experiencing disparities.

Abstract Many seafood products marketed as “sustainable” are not. More exacting sustainability standards are needed to respond to a fast-changing world and support United Nations SDGs. Future fisheries must operate on principles that minimise impacts on marine life, adapt to climate change and allow regeneration of depleted biodiversity, while supporting and enhancing the health, wellbeing and resilience of people and communities. We set out 11 actions to achieve these goals.

Abstract Objective The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha‐actinin‐2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha‐actinin‐2 is to link actin and titin to the sarcomere Z‐disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype–phenotype correlations in ACTN2‐related diseases, actininopathies, persists. Methods Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype–phenotype correlations of actininopathies using clinical data from several patients carrying these variants. Results The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha‐actinin‐2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha‐actinin‐2 aggregates. Interpretation The results suggest that alpha‐actinin‐2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein‐extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies.

Abstract Background Electronic patient-reported outcome (ePRO) systems can be used to engage patients in remote symptom monitoring to support postoperative care. We interviewed thoracic surgery patients with ePRO experience to identify factors that influenced use of ePROs to report their symptoms post-discharge. Method This qualitative study used semi-structured telephone interviews with adults who underwent major thoracic surgery at an academic medical center in North Carolina. Individuals who enrolled in symptom monitoring, completed at least one ePRO survey, and were reachable by phone for the interview were included. The ePRO surveys assessed 10 symptoms, including validated Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures and thoracic surgery-specific questions. Surveys, offered via web-based and automated telephone options, were administered for four weeks post-discharge with alerts sent to clinicians for concerning symptoms. The interviews were guided by the Capability, Opportunity, Motivation model for behavior change (COM-B) and examined factors that influenced patients’ completion of ePRO surveys post-discharge. Team members independently coded interviews and identified themes, informed by COM-B. We report descriptive statistics (demographics, number of surveys completed) and themes organized by COM-B components. Results Of 28 patients invited, 25 (89%) completed interviews from July to October 2022. Participants were a median 58 years, 56% female, 80% White, and 56% had a history of malignancy. They completed 131/150 (87%) possible ePRO surveys. For capability, participants reported building ePROs into their routine and having the skills and knowledge, but lacking physical and emotional energy, to complete ePROs. For opportunity, participants identified the ease and convenience of accessing ePROs and providers’ validation of ePROs. Motivators were perceived benefits of a deepening connection to their clinical team, improved symptom management for themselves and others, and self-reflection about their recovery. Factors limiting motivation included lack of clarity about the purpose of ePROs and a disconnect between symptom items and individual recovery experience. Conclusions Patients described being motivated to complete ePROs when reinforced by clinicians and considered ePROs as valuable to their post-discharge experience. Future work should enhance ePRO patient education, improve provider alerts and communications about ePROs, and integrate options to capture patients’ complex health journeys.

Abstract Background A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. Results Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. Conclusions Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Abstract Background Adoption of colorectal cancer (CRC) screening has lagged in community health center (CHC) populations in the USA. To address this implementation gap, we developed a multilevel intervention to improve screening in CHCs in our region. We used the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to guide this effort. Here, we describe the use of implementation strategies outlined in the Expert Recommendations for Implementing Change (ERIC) compilation in both the Exploration and Preparation phases of this project. During these two EPIS phases, we aimed to answer three primary questions: (1) What factors in the inner and outer contexts may support or hinder colorectal cancer screening in North Carolina CHCs?; (2) What evidence-based practices (EBPs) best fit the needs of North Carolina CHCs?; and (3) How can we best integrate the selected EBPs into North Carolina CHC systems? Methods During the Exploration phase, we conducted local needs assessments, built a coalition, and conducted local consensus discussions. In the Preparation phase, we formed workgroups corresponding to the intervention’s core functional components. Workgroups used cyclical small tests of change and process mapping to identify implementation barriers and facilitators and to adapt intervention components to fit inner and outer contexts. Results Exploration activities yielded a coalition of stakeholders, including two rural CHCs, who identified barriers and facilitators and reached consensus on two EBPs: mailed FIT and navigation to colonoscopy. Stakeholders further agreed that the delivery of those two EBPs should be centralized to an outreach center. During Preparation, workgroups developed and refined protocols for the following centrally-delivered intervention components: a registry to identify and track eligible patients, a centralized system for mailing at-home stool tests, and a process to navigate patients to colonoscopy after an abnormal stool test. Conclusions This description may be useful both to implementation scientists, who can draw lessons from applied implementation studies such as this to refine their implementation strategy typologies and frameworks, as well as to implementation practitioners seeking exemplars for operationalizing strategies in early phases of implementation in healthcare.

The world is struggling to limit greenhouse gas emissions and reduce the human footprint on nature. We therefore urgently need to think about how to achieve more with actions to address mounting challenges for human health and wellbeing from biodiversity loss, climate change effects, and unsustainable economic and social development. Nature-based Solutions (NBS) have emerged as a systemic approach and an important component of the response to these challenges. In marine and coastal spaces, NBS can contribute to improved environmental health, climate change mitigation and adaptation, and a more sustainable blue economy, if implemented to a high standard. However, NBS have been largely studied for terrestrial – particularly urban – systems, with limited uptake thus far in marine and coastal areas, despite an abundance of opportunities. Here, we provide explanations for this lag and propose the following three research priorities to advance marine and coastal NBS: (1) Improve understanding of marine and coastal biodiversity-ecosystem services relationships to support NBS better designed for rebuilding system resilience and achieving desired ecological outcomes under climate change; (2) Provide scientific guidance on how and where to implement marine and coastal NBS and better coordinate strategies and projects to facilitate their design, effectiveness, and value through innovative synergistic actions; (3) Develop ways to enhance marine and coastal NBS communication, collaboration, ocean literacy and stewardship to raise awareness, co-create solutions with stakeholders, boost public and policy buy-in, and potentially drive a more sustained investment. Research effort in these three areas will help practitioners, policy-makers and society embrace NBS for managing marine and coastal ecosystems for tangible benefits to people and marine life.

Background: Shortages in healthcare workers affects the overall delivery and effectiveness of the provision of healthcare. There are currently insufficient pharmacists working in the community sector in Ireland. While several studies have reported on the factors leading to retention in the medical and nursing profession, there is an absence of robust research examining retention within the pharmacist workforce in Ireland. Objective: To identify and understand the range of factors currently at play in the community pharmacy sector in Ireland which influence the decision-making process for pharmacists deciding whether or not to continue to practice as a community pharmacist. Method: A cross-sectional qualitative descriptive study was used to investigate the factors influencing community pharmacist retention as elicited from the lived experiences of 23 pharmacists. Study recruitment was undertaken using both convenience and purposive sampling. Qualitative content analysis was used to analyze the interview data to identify and explore themes. Results: A broad and diverse range of factors were identified as affecting community pharmacist retention including working conditions, career fulfilment and progression, regulatory and administrative burden, the commercial focus within community practice, lack of representation and their overall health and well-being. Conclusion: The findings show that there are a number of factors which either individually or cumulatively influence a pharmacist's decision to stay in or leave community practice. Various areas for change were identified, which if addressed are considered likely to improve retention in the sector. These include enhanced terms and working conditions, better acknowledgement and resourcing of professional activities, improved opportunities for career progression, reforms to the regulatory model including the personal accountability of a supervising pharmacist for all of the pharmacy's professional activities, a more streamlined model of reimbursement and more effective collective representation.

Completion rates for follow-up colonoscopies after an abnormal fecal immunochemical test (FIT) are suboptimal in federally qualified health center (FQHC) settings. We implemented a screening intervention that included mailed FIT outreach to North Carolina FQHC patients from June 2020 to September 2021 and centralized patient navigation to support patients with abnormal FITs in completing follow-up colonoscopy. We evaluated the reach and effectiveness of navigation using electronic medical record data and navigator call logs detailing interactions with patients. Reach assessments included the proportion of patients successfully contacted by phone and who agreed to participate in navigation, intensity of navigation provided (including types of barriers to colonoscopy identified and total navigation time), and differences in these measures by socio-demographic characteristics. Effectiveness outcomes included colonoscopy completion, timeliness of follow-up colonoscopy (i.e., within 9 months), and bowel prep adequacy. Among 514 patients who completed a mailed FIT, 38 patients had an abnormal result and were eligible for navigation. Of these, 26 (68%) accepted navigation, 7 (18%) declined, and 5 (13%) could not be contacted. Among navigated patients, 81% had informational needs, 38% had emotional barriers, 35% had financial barriers, 12% had transportation barriers, and 42% had multiple barriers to colonoscopy. Median navigation time was 48.5 min (range: 24–277 min). Colonoscopy completion differed across groups – 92% of those accepting navigation completed colonoscopy within 9 months, versus 43% for those declining navigation. We found that centralized navigation was widely accepted in FQHC patients with abnormal FIT, and was an effective strategy, resulting in high colonoscopy completion rates.

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 catalytic activity in viral replication, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site. While substitution to alanine (N40A) reduced catalytic activity by ~10-fold, mutations to aspartic acid (N40D) reduced activity by ~100-fold relative to wild-type. Importantly, the N40A mutation rendered Mac1 unstable in vitro and lowered expression levels in bacterial and mammalian cells. When incorporated into SARS-CoV-2 molecular clones, the N40D mutant only modestly affected viral fitness in immortalized cell lines, but reduced viral replication in human airway organoids by 10-fold. In mice, the N40D mutant replicated at >1000-fold lower levels compared to the wild-type virus while inducing a robust interferon response; all animals infected with the mutant virus survived infection. Our data validate the critical role of SARS-CoV-2 NSP3 Mac1 catalytic activity in viral replication and as a promising therapeutic target to develop antivirals.

Abstract Accurate, unbiased and concise synthesis of available evidence following clear methodology and transparent reporting is necessary to support effective environmental policy and management decisions. Without this, less reliable and/or less objective reviews of evidence could inform decision making, leading to ineffective, resource wasteful interventions with potential for unintended consequences. We evaluated the reliability of over 1000 evidence syntheses (reviews and overviews) published between 2018 and 2020 that provide evidence on the impacts of human activities or effectiveness of interventions relevant to environmental management. The syntheses are drawn from the Collaboration for Environmental Evidence Database of Evidence Reviews (CEEDER), an online, freely available evidence service for evidence users that assesses the reliability of evidence syntheses using a series of published criteria. We found that the majority of syntheses have problems with transparency, replicability and potential for bias. Overall, our results suggest that most recently published evidence syntheses are of low reliability to inform decision making. Reviews that followed guidance and reporting standards for evidence synthesis had improved assessment ratings, but there remains substantial variation in the standard of reviews amongst even these. Furthermore, the term ‘systematic review’, which implies conformity with a methodological standard, was frequently misused. A major objective of the CEEDER project is to improve the reliability of the global body of environmental evidence reviews. To this end we outline freely available online resources to help improve review conduct and reporting. We call on authors, editors and peer reviewers to use these resources to ensure more reliable syntheses in the future.

Abstract Background Economic evaluations of the implementation of health-related evidence-based interventions (EBIs) are conducted infrequently and, when performed, often use a limited set of quantitative methods to estimate the cost and effectiveness of EBIs. These studies often underestimate the resources required to implement and sustain EBIs in diverse populations and settings, in part due to inadequate scoping of EBI boundaries and underutilization of methods designed to understand the local context. We call for increased use of diverse methods, especially the integration of quantitative and qualitative approaches, for conducting and better using economic evaluations and related insights across all phases of implementation. Main body We describe methodological opportunities by implementation phase to develop more comprehensive and context-specific estimates of implementation costs and downstream impacts of EBI implementation, using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. We focus specifically on the implementation of complex interventions, which are often multi-level, resource-intensive, multicomponent, heterogeneous across sites and populations, involve many stakeholders and implementation agents, and change over time with respect to costs and outcomes. Using colorectal cancer (CRC) screening EBIs as examples, we outline several approaches to specifying the “boundaries” of EBI implementation and analyzing implementation costs by phase of implementation. We describe how systems mapping and stakeholder engagement methods can be used to clarify EBI implementation costs and guide data collection—particularly important when EBIs are complex. In addition, we discuss the use of simulation modeling with sensitivity/uncertainty analyses within implementation studies for projecting the health and economic impacts of investment in EBIs. Finally, we describe how these results, enhanced by careful data visualization, can inform selection, adoption, adaptation, and sustainment of EBIs. Conclusion Health economists and implementation scientists alike should draw from a larger menu of methods for estimating the costs and outcomes associated with complex EBI implementation and employ these methods across the EPIS phases. Our prior experiences using qualitative and systems approaches in addition to traditional quantitative methods provided rich data for informing decision-making about the value of investing in CRC screening EBIs and long-term planning for these health programs. Future work should consider additional opportunities for mixed-method approaches to economic evaluations.

The long-term provision of ocean ecosystem services depends on healthy ecosystems and effective sustainable management. Understanding public opinion about marine and coastal ecosystems is important to guide decision-making and inform specific actions. However, available data on public perceptions on the interlinked effects of climate change, human impacts and the value and management of marine and coastal ecosystems are rare. This dataset presents raw data from an online, self-administered, public awareness survey conducted between November 2021 and February 2022 which yielded 709 responses from 42 countries. The survey was released in four languages (English, French, Spanish and Italian) and consisted of four main parts: (1) perceptions about climate change; (2) perceptions about the value of, and threats to, coasts, oceans and their wildlife, (3) perceptions about climate change response; and (4) socio-demographic information. Participation in the survey was voluntary and all respondents provided informed consent after reading a participant information form at the beginning of the survey. Responses were anonymous unless respondents chose to provide contact information. All identifying information has been removed from the dataset. The dataset can be used to conduct quantitative analyses, especially in the area of public perceptions of the interlinkages between climate change, human impacts and options for sustainable management in the context of marine and coastal ecosystems. The dataset is provided with this article, including a copy of the survey and participant information forms in all four languages, data and the corresponding codebook.

Vaccination for Human Papillomavirus (HPV) is important to reduce rates of cervical and oropharyngeal cancer. We aimed to evaluate if a program to initiate HPV vaccination at 9 years improved initiation and completion rates by 13 years of age. Data on empaneled patients aged 9–13 years from January 1, 2021 to August 30, 2022 were abstracted from the electronic health record. Primary outcome measures included HPV vaccination initiation and series completion by 13 years of age. The secondary outcome measure was missed opportunities for HPV vaccination. In total, 25,888 patients were included (12,433 pre-intervention, and 13,455 post-intervention). The percentage of patients aged 9–13 with an in-person visit who received at least 1 dose of HPV vaccine increased from 30% pre-intervention to 43% post-intervention. The percentage of patients who received 2 doses of vaccine increased from 19.3% pre-intervention to 42.7% post-intervention. For the overall population seen in-person, initiation of HPV vaccination by age 13 years increased from 42% to 54%. HPV completion increased as well (13% to 18%). HPV vaccination initiation at 9 years of age may be an acceptable and effective approach to improving vaccination rates.

Background Reforms to models of health and care regulation internationally have adapted to address the challenges associated with regulating healthcare professionals. Pharmacists in Ireland entered a new era of regulation with the enactment of the Pharmacy Act in 2007 which significantly updated the law regulating pharmacy in Ireland and expanded the regulatory scope considerably. An earlier study in 2017 examined the experiences of 20 community pharmacists of the Act. This follow-up study aimed to expand the scope of the original study to all community pharmacists in Ireland, to report their “lived experience” of the regulatory model introduced by the Act, assessing its impact on their professional practice using the principles of “better regulation”. Methods Survey methodology was used to assess the perception of all community pharmacists registered with the Pharmaceutical Society of Ireland of the Act, as implemented, on their practice using an experimental design based on the seven principles of “Better Regulation”. Descriptive statistics analyzed quantitative responses while answers from open-ended questions were analyzed using a combination of a modified framework analysis and a qualitative content analysis. Results Respondents agreed that the Act was necessary, although its implementation by the regulator was largely not viewed as fulfilling the remaining “Better Regulation” principles of being effective, proportional, consistent, agile, accountable and transparent. In particular, its proportionality was questioned. This resulted in pharmacists perceiving that their professional competency to act in the best interests of their patients was not appropriately acknowledged by the regulator, which in turn compromised their ability to provide optimal care for their patients. Conclusion While healthcare professional regulation must primarily be concerned with public protection, it must also have regard to its impact on those delivering healthcare services. The findings highlight the challenge internationally of balancing rigidity and flexibility in professional health and care regulation, and the importance of a regulatory conversation occurring between those regulating and those regulated. This would serve to promote mutual learning and understanding to create a responsive approach to regulation, underpinned by mutual trust, effective risk assessment and adherence to the principles of “Better Regulation”.

Background: Chlamydia trachomatis and Neisseria gonorrhea are the most reported sexually transmitted infections in the United States. Testing rates remain suboptimal and may be subject to implicit bias. We evaluated the effectiveness of an opt-out chlamydia and gonorrhea testing program for adolescents and young adults in improving testing rates and promoting equity. Methods: An opt-out testing program that standardized testing to once annually for 14 to 24-year-old patients was implemented across 28 federally qualified health centers spanning 4 specialties. A quasi-experimental design using interrupted time series analyses evaluated testing and infection rates between baseline, intervention, and pandemic-associated test shortage periods. Reduction in testing inequities based on sex, race, ethnicity, insurance, and language preference were also examined. Results: A total of 57 452 encounters during the baseline, 17 320 during the intervention, and 26 993 during the test supply shortage periods were included. Testing increased from 66.8% to 81.0% (14.2% absolute increase) between baseline and intervention periods. Pediatric clinics demonstrated the largest improvement compared to other settings (absolute increase 30.9%). We found significant reductions in testing inequities for language preference ( P

Abstract Background In several recent articles, authors have called for aligning the fields of implementation and improvement science. In this paper, we call for implementation science to also align with improvement practice. Multiple implementation scholars have highlighted the importance of designing implementation strategies to fit the existing culture, infrastructure, and practice of a healthcare system. Worldwide, healthcare systems are adopting improvement models as their primary approach to improving healthcare delivery and outcomes. The prevalence of improvement models raises the question of how implementation scientists might best align their efforts with healthcare systems’ existing improvement infrastructure and practice. Main body We describe three challenges and five benefits to aligning implementation science and improvement practice. Challenges include (1) use of different models, terminology, and methods, (2) a focus on generalizable versus local knowledge, and (3) limited evidence in support of the effectiveness of improvement tools and methods. We contend that implementation science needs to move beyond these challenges and work toward greater alignment with improvement practice. Aligning with improvement practice would benefit implementation science by (1) strengthening research/practice partnerships, (2) fostering local ownership of implementation, (3) generating practice-based evidence, (4) developing context-specific implementation strategies, and (5) building practice-level capacity to implement interventions and improve care. Each of these potential benefits is illustrated in a case study from the Centers for Disease Control and Prevention’s Cancer Prevention and Control Research Network. Conclusion To effectively integrate evidence-based interventions into routine practice, implementation scientists need to align their efforts with the improvement culture and practice that is driving change within healthcare systems worldwide. This paper provides concrete examples of how researchers have aligned implementation science with improvement practice across five implementation projects.

Abstract Background Anthropogenic degradation of marine ecosystems is widely accepted as a major social-ecological problem. The growing urgency to manage marine ecosystems more effectively has led to increasing application of spatial management measures (marine protected areas [MPAs], sectoral [e.g. fishery] closures and marine spatial planning [marine plans]). Understanding the methodologies used to evaluate the effectiveness of these measures against social, economic, and ecological outcomes is key for designing effective monitoring and evaluation programmes. Methods We used a pre-defined and tested search string focusing on intervention and outcome terms to search for relevant studies across four bibliographic databases, Google Scholar, 39 organisational websites, and one specialist data repository. Searches were conducted in English and restricted to the period 2009 to 2019 to align with current UK marine policy contexts. Relevant studies were restricted to UK-relevant coastal countries, as identified by key stakeholders. Search results were screened for relevance against pre-defined eligibility criteria first at title and abstract level, and then at full text. Articles assessed as not relevant at full text were recorded with reasons for exclusion. Two systematic map databases of meta-data and coded data from relevant primary and secondary studies, respectively, were produced. Review findings Over 19,500 search results were identified, resulting in 391 relevant primary articles, 33 secondary articles and 49 tertiary reviews. Relevant primary articles evaluated spatial management measures across a total of 22 social, economic and ecological outcomes; only 2.8% considered all three disciplines, with most focused exclusively on ecological (67.8%) or social (13.3%) evaluations. Secondary articles predominately focused on ecological evaluations (75.8%). The majority of the primary and secondary evidence base aimed to evaluate the effectiveness of MPAs (85.7% and 90.9% respectively), followed by fisheries closures (12.5%; 3.0%) with only 1.8% of primary, and 6.1% of secondary, articles focused on marine plans or on MPAs and fisheries closures combined. Most evaluations reported within primary articles were conducted for a single site (60.4%) or multiple individual sites (32.5%), with few evaluating networks of sites (6.9%). Secondary articles mostly evaluated multiple individual sites (93.9%). Most (70.3%) primary articles conducted principal evaluations, i.e. basic description of effects; 29.4% explored causation; and 0.3% undertook benefit evaluations. Secondary articles predominately explored causation (66.7%) with the remainder conducting principal evaluations. Australia (27.4%), the USA (18.4%) and the UK (11.3%) were most frequently studied by primary articles, with secondary articles reporting mostly global (66.7%) or European (18.2%) syntheses. Conclusions The systematic map reveals substantial bodies of evidence relating to methods of evaluating MPAs against ecological outcomes. However, key knowledge gaps include evaluation across social and economic outcomes and of overall merit and/or worth (benefit evaluation), as well as of: marine plans; networks of sites; real-time, temporary or seasonal closures; spatial management within offshore waters, and lagoon or estuary environments. Although the evidence base has grown over the past two decades, information to develop comprehensive evaluation frameworks remains insufficient. Greater understanding on how to evaluate the effectiveness of spatial management measures is required to support improved management of global ocean resources and spaces.

Abstract Understanding patient accumulation of comorbidities can facilitate healthcare strategy and personalized preventative care. We applied a directed network graph to electronic health record (EHR) data and characterized comorbidities in a cohort of healthy veterans undergoing screening colonoscopy. The Veterans Affairs Cooperative Studies Program #380 was a prospective longitudinal study of screening and surveillance colonoscopy. We identified initial instances of three-digit ICD-9 diagnoses for participants with at least 5 years of linked EHR history (October 1999 to December 2015). For diagnoses affecting at least 10% of patients, we calculated pairwise chronological relative risk (RR). iGraph was used to produce directed graphs of comorbidities with RR > 1, as well as summary statistics, key diseases, and communities. A directed graph based on 2210 patients visualized longitudinal development of comorbidities. Top hub (preceding) diseases included ischemic heart disease, inflammatory and toxic neuropathy, and diabetes. Top authority (subsequent) diagnoses were acute kidney failure and hypertensive chronic kidney failure. Four communities of correlated comorbidities were identified. Close analysis of top hub and authority diagnoses demonstrated known relationships, correlated sequelae, and novel hypotheses. Directed network graphs portray chronologic comorbidity relationships. We identified relationships between comorbid diagnoses in this aging veteran cohort. This may direct healthcare prioritization and personalized care.

Background. Catastrophic antiphospholipid syndrome (CAPS) is an autoimmune thrombogenic disorder of small and large vessels caused by autoantibodies against phospholipids and phospholipid-binding proteins. This severe form of antiphospholipid syndrome (APS) presents clinically with simultaneous life-threatening multiorgan thrombosis and the presence of two or more persistent antiphospholipid antibodies (APL) confirmed on testing 12 weeks apart. Case Presentation. We describe a case report of a 66-year-old woman with detected antinuclear antibodies (ANA) pretransplant diagnosed with CAPS following orthotopic liver transplant. The patient had acute respiratory failure; Doppler ultrasound and CT angiogram confirmed thrombosis in the hepatic artery, subsequent occlusion of the jump graft, and a splenic infarct. Hypercoagulability workup showed elevated levels of anticardiolipin IgG and beta-2-glycoprotein IgG/IgM and positive lupus anticoagulant, treated with steroids and anticoagulation. The patient was discharged after one month and was transitioned from heparin to life-long warfarin. Conclusion. Our patient provided a standard presentation of CAPS with abnormal pretransplant levels of antinuclear antibodies (ANA). Although there have been studies investigating the relationship between anticardiolipin antibodies and lupus anticoagulants and APS, the relationship between pretransplant positive ANA or antimitochondrial antibodies (AMA) and CAPS has yet to be explored. Further studies will be needed to determine the significance of these antibodies. We recommend preoperative APL testing for patients with positive ANA and AMA at preliver transplant presentation.

Abstract The decision of the UK to leave the EU has far‐reaching, and often shared, implications for agriculture and fisheries. To ensure the future sustainability of the UK’s agricultural and fisheries systems, we argue that it is essential to grasp the opportunity that Brexit is providing to develop integrated policies that improve the management and protection of the natural environments, upon which these industries rely. This article advances a stakeholder informed vision of the future design of UK agriculture and fisheries policies. We assess how currently emerging UK policy will need to be adapted in order to implement this vision. Our starting point is that Brexit provides the opportunity to redesign current unsustainable practices and can, in principle, deliver a sustainable future for agriculture and fisheries. Underpinning policies with an ecosystem approach, explicit inclusion of public goods provision and social welfare equity were found to be key provisions for environmental, agricultural and fishery sustainability. Recognition of the needs of, and innovative practices in, the devolved UK nations is also required as the new policy and regulatory landscape is established. Achieving the proposed vision will necessitate drawing on best practice and creating more coherent and integrated food, environment and rural and coastal economic policies. Our findings demonstrate that “bottom‐up” and co‐production approaches will be key to the development of more environmentally sustainable agriculture and fisheries policies to underpin prosperous livelihoods. However, delivering this vision will involve overcoming significant challenges. The current uncertainty over the nature and timing of the UK’s Brexit agreement hinders forward planning and investment while diverting attention away from further in‐depth consideration of environmental sustainability. In the face of this uncertainty, much of the UK’s new policy on the environment, agriculture and fisheries is therefore ambitious in vision but light on detail. Full commitment to co‐production of policy with devolved nations and stakeholders also appears to be lacking, but will be essential for effective policy development and implementation. A free Plain Language Summary can be found within the Supporting Information of this article.

Abstract Background Adapting screening strategy to colorectal cancer (CRC) risk may improve efficiency for all stakeholders however limited tools for such risk stratification exist. Colorectal cancers usually evolve from advanced neoplasms that are present for years. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool, which calculates future risk of CRC, to determine whether it could be used to predict current advanced neoplasia (AN) in a veteran cohort undergoing a baseline screening colonoscopy. Methods This was a prospective assessment of the relationship between future CRC risk predicted by the NCI tool, and the presence of AN at screening colonoscopy. Family, medical, dietary and physical activity histories were collected at the time of screening colonoscopy and used to calculate absolute CRC risk at 5, 10 and 20 years. Discriminatory accuracy was assessed. Results Of 3121 veterans undergoing screening colonoscopy, 94% had complete data available to calculate risk (N = 2934, median age 63 years, 100% men, and 15% minorities). Prevalence of AN at baseline screening colonoscopy was 11 % (N = 313). For tertiles of estimated absolute CRC risk at 5 years, AN prevalences were 6.54% (95% CI, 4.99, 8.09), 11.26% (95% CI, 9.28-13.24), and 14.21% (95% CI, 12.02-16.40). For tertiles of estimated risk at 10 years, the prevalences were 6.34% (95% CI, 4.81-7.87), 11.25% (95% CI, 9.27-13.23), and 14.42% (95% CI, 12.22-16.62). For tertiles of estimated absolute CRC risk at 20 years, current AN prevalences were 7.54% (95% CI, 5.75-9.33), 10.53% (95% CI, 8.45-12.61), and 12.44% (95% CI, 10.2-14.68). The area under the curve for predicting current AN was 0.60 (95% CI; 0.57-0.63, p

Abstract Background Anthropogenic degradation of marine ecosystems is widely accepted as a major social-ecological problem. The growing urgency to better manage marine ecosystems has led to the increasing application of ‘spatial management measures’ including marine protected areas, sectoral (e.g. fishery) closures, and marine spatial planning. However, the designation of varied spatial management regimes is just the first step; achievement of objectives relies upon effective implementation, monitoring, evaluation and adaptation. Despite spatial management being a core component of the marine management portfolio, to our knowledge, there is no systematic overview of the evidence on methodologies available, and employed, to monitor and evaluate their effectiveness across social, economic and ecological outcomes. Methods This systematic map will examine existing evidence describing methodologies for monitoring the effects, and evaluating the effectiveness, of marine spatial management across ecological, social and economic outcomes. Our aim is to provide a resource for decision-makers, primarily in the UK but also internationally, that supports effective marine management, and to describe the current evidence base. Identification and evaluation of relevant studies will therefore be restricted to coastal countries identified by our Stakeholder Group as being relevant to the UK, and searches will be restricted to the period 2009 to 2019 to align with the current UK policy context. Searches for relevant grey and academic literature, published in English, will be conducted in four bibliographic search engines, Google Scholar, 38 organisational websites and one specialist data repository. Eligibility screening will be conducted first at title and abstract level, and then at full text. Coding and meta-data extraction from eligible studies will include: bibliographic information, general information about the spatial management measure studied, and methodological information on the monitoring and evaluation undertaken. Consistency checking amongst reviewers will be undertaken during screening, coding and data extraction phases. The outcome of the systematic map will be a database that displays the meta-data of identified relevant studies. Findings will be presented in a descriptive report detailing the evaluation approaches and analytical methodologies employed, and data collection methods applied and/or data required by relevant studies to inform evaluations on the effectiveness of marine spatial management measures.

Abstract Background Colorectal cancer (CRC) screening is underutilized by Medicaid enrollees and the uninsured. Multiple national and state policies were enacted from 2010 to 2014 to increase access to Medicaid and to promote CRC screening among Medicaid enrollees. We aimed to determine the impact of these policies on screening initiation among newly enrolled Oregon Medicaid beneficiaries age-eligible for CRC screening. Methods We identified national and state policies affecting Medicaid coverage and preventive services in Oregon during 2010–2014. We used Oregon Medicaid claims data from 2010 to 2015 to conduct a cohort analysis of enrollees who turned 50 and became age-eligible for CRC screening (a prevention milestone, and an age at which guideline-concordant screening can be assessed within a single year) during each year from 2010 to 2014. We calculated risk ratios to assess whether first year of Medicaid enrollment and/or year turned 50 was associated with CRC screening initiation. Results We identified 14,576 Oregon Medicaid enrollees who turned 50 during 2010–2014; 2429 (17%) completed CRC screening within 12 months after turning 50. Individuals newly enrolled in Medicaid in 2013 or 2014 were 1.58 and 1.31 times more likely, respectively, to initiate CRC screening than those enrolled by 2010. A primary care visit in the calendar year, having one or more chronic conditions, and being Hispanic was also associated with CRC screening initiation. Discussion The increased uptake of CRC screening in 2013 and 2014 is associated with the timing of policies such as Medicaid expansion, enhanced federal matching for preventive services offered to Medicaid enrollees without cost sharing, and formation of Medicaid accountable care organizations, which included CRC screening as an incentivized quality metric.

Concussions have been shown to result in autonomic dysfunction and altered cerebral vascular function. We tested the hypothesis that concussed athletes (CA) would have altered cerebral vascular function during acute decreases and increases in blood pressure compared to healthy controls (HC). Ten CA (age: 20 ± 2 y, 7 females) and 10 HC (age: 21 ± 2 y, 6 females) completed 5 min of lower body negative pressure (LBNP; −40 mmHg) and 5 min of lower body positive pressure (LBPP; 20 mmHg). Protocols were randomized and separated by 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Values are reported as change from baseline to the last minute achieved (LBNP) or 5 min (LBPP). There were no differences in baseline values between groups. During LBNP, there were no differences in the change for MAP (CA: −23 ± 18 vs. HC: −21 ± 17 cm/s; P = 0.80) or MCAv (CA: −13 ± 8 vs. HC: −18 ± 9 cm/s; P = 0.19). The change in CVR was different between groups (CA: −0.08 ± 0.26 vs. HC: 0.18 ± 0.24 mmHg/cm/s; P = 0.04). Total LBNP time was lower for CA (204 ± 92 s) vs. HC (297 ± 64 s; P = 0.04). During LBPP, the change in MAP was not different between groups (CA: 13 ± 6 vs. HC: 10 ± 7 mmHg; P = 0.32). The change in MCAv (CA: 7 ± 6 vs. HC: −4 ± 13 cm/s; P = 0.04) and CVR (CA: −0.06 ± 0.27 vs. HC: 0.38 ± 0.41 mmHg/cm/s; P = 0.03) were different between groups. CA exhibited impaired tolerance to LBNP and had a different cerebral vascular response to LBPP compared to HC.

Introduction Secure forensic mental health services have a dual role, to treat mental illness and reduce violent recidivism. Those admitted to secure forensic services have a significant history of violence and treatment needs in multiple domains including psychiatric illness, violence and other areas such as substance misuse and physical health. Objectives The aim of this study was to ascertain if the units in a medium secure forensic hospital are stratified according to individual risks and needs. We also aimed to clarify if there were differences in the symptom level, risks and needs of those with and without community leave and to clarify the risks and needs of the female patients and ID patients. Methods This is a cross sectional study a cohort of patients (n=138) in a secure forensic hospital. Results There was a total of 138 patients, the majority of whom were male (n=123, 89.1%). The most common diagnosis was schizophrenia (n=99, 71.7%). Placements in the care pathway of the medium secure forensic hospital were associated with level of symptomatology (PANSS positive), dynamic violence risk (F=26.880,P

Federal agencies, including the Department of Veterans Affairs (VA), have prioritized improved access to scientific data and results collected through federally funded research. Our VA Cooperative Studies Program Epidemiology Center in Durham, North Carolina (CSPEC-Durham) assembled a repository of data and specimens collected through multiple studies on Veteran health issues to facilitate future research in these areas. We developed a single protocol, request process that includes scientific and ethical review of all applications, and a database architecture using metadata (common variable descriptors) to securely store and share data across diverse studies. In addition, we created a mechanism to allow data and specimens collected through older studies in which re-use was not addressed in the study protocol or consent forms to be shared if the future research is within the scope of the original consent. Our CSPEC-Durham Data and Specimen Repository currently includes research data, genomic data, and study specimens (e.g., DNA, blood) for three content areas: colorectal cancer, amyotrophic lateral sclerosis, and Gulf War research. The linking of the study specimens and research data can support additional genetic analyses and related research to improve Veterans' health.

Hepatitis B virus (HBV) reactivation may occur with high risk immunosuppression, such as anti‐cluster of differentiation (CD)20 antibodies (Abs). Appropriate HBV prophylaxis during anti‐CD20 Ab therapy averts hepatitis, chemotherapy disruption, and death. Serologic evidence of prior HBV exposure is present in one in nine veterans in the Veterans Health Administration (VHA). In 2014, most (61%‐73%) patients in the VHA who were receiving anti‐CD20 Ab treatment underwent HBV testing, yet 90% and antiviral prophylaxis to >80%.

Abstract Evidence reviews are a key mechanism for incorporating extensive, complex and specialised evidence into policy and practice, and in guiding future research. However, evidence reviews vary in scope and methodological rigour, creating several risks for decision-makers: decisions may be informed by less reliable reviews; apparently conflicting interpretations of evidence may obfuscate decisions; and low quality reviews may create the perception that a topic has been adequately addressed, deterring new syntheses (cryptic evidence gaps). We present a new approach, evidence review mapping, designed to produce a visual representation and critical assessment of the review landscape for a particular environmental topic or question. By systematically selecting and describing the scope and rigour of each review, this helps guide non-specialists to the most relevant and methodologically reliable reviews. The map can also direct future research through the identification of evidence gaps (whether cryptic or otherwise) and redundancy (multiple reviews on similar questions). We consider evidence review mapping a complementary approach to systematic reviews and systematic maps of primary literature and an important tool for facilitating evidence-based decision-making and research efficiency.

The Firth of Clyde, on the west coast of Scotland, was once one of the most productive fishing grounds in Europe. However, successive decades of poor management and overfishing led to a dramatic loss of biodiversity and the collapse of finfish fisheries. In response, concerned local residents on the Isle of Arran, which lies in the middle of the Clyde, formed the Community of Arran Seabed Trust (COAST) in 1995. After 13 years of campaigning, a small (2.67 km2) area in Lamlash Bay became Scotland’s first no-take zone (NTZ) in 2008, and only the second in the UK. Since protection, biodiversity has increased substantially, along with the size, age and density of commercially important species such as the king scallop, Pecten maximus, and the European lobster, Homarus gammarus. Arguably more important, however, is the influence the Lamlash Bay NTZ and COAST have had on UK marine protection in general. Most notably, detailed research has created a case study that clearly demonstrates the benefits of protection in an area where little such evidence is available. This case has been used repeatedly to support efforts for increased protection of UK waters to help rebuild marine ecosystems and enhance their resilience in an uncertain future. In Scotland specifically, lobbying by COAST led to the designation of a much larger marine protected area (MPA, >250 km2) around the south of Arran, one of 30 new MPAs in the country. Evidence from Lamlash Bay has supported development of strong protection for these MPAs, seeing off lobbyist efforts to weaken management. Arran’s conservation success has been recognized internationally and is inspiring greater involvement of local communities around the UK, and further afield, to take the destiny of their coastal waters into their own hands. Successful marine conservation begins at home.

Abstract Background Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration. Methods Women (n = 105) aged 18–50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety. Results Participants on average had BMI of 35.1 ± 6.5 kg/m2and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (β = .241, SE = .14, p = .03) and magnification subscale (β = .311, SE = .51, p

Cape Verde in the Eastern Atlantic is typical of many island groups in supporting a wealth of endemic species both terrestrial and marine. Marine gastropod molluscs of the genus Conus, commonly known as cone snails, occur in coastal tropical waters throughout the globe, but in Cape Verde their endemism reaches its apogee with 53 out of 56 species occurring nowhere else, the majority of which are restricted to single islands and frequently to single bays. However, Cape Verde is rapidly moving to a tourism-based economy with a projected boom in infrastructure development often coincidental with the shallow-water habitat of many range-restricted Conus. The conservation assessment of Conus to standards of the International Union for the Conservation of Nature (IUCN) Red List of Endangered Species, found that 45.3% of 53 species assessed from Cape Verde are threatened or near-threatened with extinction compared to 7.4% of 579 species in the rest of the world. The only three Conus species globally assessed as Critically Endangered and on the cusp of extinction are all endemic to Cape Verde. Our analysis of Conus species distribution, together with spatial data of coastal protected areas and tourism development zones, identify important areas for future research and new marine protection. Our findings show that endemism with its associated risks for Conus in Cape Verde has worldwide parallels with many non-marine taxa, while our proposed strategy for Conus conservation extends beyond the confines of the country and this taxonomic group.

Coastal nations have embarked on a rapid program of marine protected area (MPA) establishment, incentivised by the approaching 2020 deadline of United Nations global marine protection targets. Alongside, efforts are underway to extend protection into areas beyond national jurisdiction through a new international legally binding instrument. These developments are welcome but there are risks that in meeting them, nations will still fail to supply adequate protection to marine life. An increasing number of MPAs protect the seabed while the water column remains open to fishing. This is because vulnerable habitats in need of protection are disproportionately perceived to be those on the seabed, while the water column is viewed as much less at risk. The seabed and water column are, however, inextricably linked. Transitions between human-defined vertical ocean zones are blurred, with animals and oceanographic features moving across depths. Here, we explore a rapidly growing literature on ecological and environmental connections through the water column, and between the water column and the seabed, to consider whether vertically stratified management is justified from an ecological standpoint. We find that emerging research increasingly links upper-ocean communities and processes to seabed ecology and biogeochemistry suggesting that exploitation of the water column is likely to have a significant and widely distributed footprint in the deep-sea. We conclude that there is a strong a priori case for surface to seabed protection within MPAs, and that this should be the default, precautionary approach to safeguard intact ecosystems with as near to natural function as possible. Keywords: Areas beyond national jurisdiction, Convention on Biological Diversity, High seas, Marine protected areas, Pelagic-benthic coupling, Sustainable Development Goal 14