Health care utilization and behavior changes after workplace genetic testing at a large US health care system.

PURPOSE: This study explored employee health behavior changes and health care utilization after workplace genetic testing (wGT). Wellness-program-associated wGT seeks to improve employee health, but the related health implications are unknown. METHODS: Employees of a large US health care system offering wGT (cancer, heart disease, and pharmacogenomics [PGx]) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, whereas logistic regression analyses explored correlates of responses to wGT. RESULTS: 53.9% (n = 418/776) of respondents (88.3% female, mean age = 44 years) reported receiving wGT results. 12.0% (n = 48/399) received results indicating increased risk (IR) of cancer, 9.5% (n = 38/398) had IR of heart disease, and 31.4% (n = 125/398) received informative PGx results. IR results for cancer and/or heart disease (n = 67) were associated with health behavior changes (adjusted odds ratio: 3.23; 95% CI 1.75, 6.13; P < .001) and health care utilization (adjusted odds ratio: 8.60; 95% CI 4.43, 17.5; P < .001). Informative PGx results (n = 125) were associated with medication changes (PGx-informative: 15.2%; PGx-uninformative: 4.8%; P = .002). CONCLUSION: This study explored employee responses to wGT, contributing to the understanding of the ethical and social implications of wGT. Receiving IR results from wGT may promote health behavior changes and health care utilization in employees.

Corrigendum: Reductions in global biodiversity loss predicted from conservation spending.

This corrects the article DOI: 10.1038/nature24295.

A multi-national, video-based qualitative study to refine training guidelines for assigning an "unsafe" score in laparoscopic cholecystectomy critical view of safety.

BACKGROUND: The critical view of safety (CVS) was incorporated into a novel 6-item objective procedure-specific assessment for laparoscopic cholecystectomy (LC-CVS OPSA) to enhance focus on safe completion of surgical tasks and advance the American Board of Surgery's entrustable professional activities (EPAs) initiative. To enhance instrument development, a feasibility study was performed to elucidate expert surgeon perspectives regarding "safe" vs. "unsafe" practice. METHODS: A multi-national consortium of 11 expert LC surgeons were asked to apply the LC-CVS OPSA to ten LC videos of varying surgical difficulty using a "safe" vs. "unsafe" scale. Raters were asked to provide written rationale for all "unsafe" ratings and invited to provide additional feedback regarding instrument clarity. A qualitative analysis was performed on written responses to extract major themes. RESULTS: Of the 660 ratings, 238 were scored as "unsafe" with substantial variation in distribution across tasks and raters. Analysis of the comments revealed three major categories of "unsafe" ratings: (a) inability to achieve the critical view of safety (intended outcome), (b) safe task completion but less than optimal surgical technique, and (c) safe task completion but risk for potential future complication. Analysis of reviewer comments also identified the potential for safe surgical practice even when CVS was not achieved, either due to unusual anatomy or severe pathology preventing safe visualization. Based upon findings, modifications to the instructions to raters for the LC-CVS OPSA were incorporated to enhance instrument reliability. CONCLUSIONS: A safety-based LC-CVS OPSA has the potential to significantly improve surgical training by incorporating CVS formally into learner assessment. This study documents the perspectives of expert biliary tract surgeons regarding clear identification and documentation of unsafe surgical practice for LC-CVS and enables the development of training materials to improve instrument reliability. Learnings from the study have been incorporated into rater instructions to enhance instrument reliability.

Laparoscopic cholecystectomy critical view of safety (LC-CVS): a multi-national validation study of an objective, procedure-specific assessment using video-based assessment (VBA).

BACKGROUND: A novel 6-item objective, procedure-specific assessment for laparoscopic cholecystectomy incorporating the critical view of safety (LC-CVS OPSA) was developed to support trainee formative and summative assessments. The LC-CVS OPSA included two retraction items (fundus and infundibulum retraction) and four CVS items (hepatocystic triangle visualization, gallbladder-liver separation, cystic artery identification, and cystic duct identification). The scoring rubric for retraction consisted of poor (frequently outside of defined range), adequate (minimally outside of defined range) and excellent (consistently inside defined range) and for CVS items were "poor-unsafe", "adequate-safe", or "excellent-safe". METHODS: A multi-national consortium of 12 expert LC surgeons applied the OPSA-LC CVS to 35 unique LC videos and one duplicate video. Primary outcome measure was inter-rater reliability as measured by Gwet's AC2, a weighted measure that adjusts for scales with high probability of random agreement. Analysis of the inter-rater reliability was conducted on a collapsed dichotomous scoring rubric of "poor-unsafe" vs. "adequate/excellent-safe". RESULTS: Inter-rater reliability was high for all six items ranging from 0.76 (hepatocystic triangle visualization) to 0.86 (cystic duct identification). Intra-rater reliability for the single duplicate video was substantially higher across the six items ranging from 0.91 to 1.00. CONCLUSIONS: The novel 6-item OPSA LC CVS demonstrated high inter-rater reliability when tested with a multi-national consortium of LC expert surgeons. This brief instrument focused on safe surgical practice was designed to support the implementation of entrustable professional activities into busy surgical training programs. Instrument use coupled with video-based assessments creates novel datasets with the potential for artificial intelligence development including computer vision to drive assessment automation.

Characterising the social interaction style of autism in young adult males with fragile X syndrome.

BACKGROUND: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS. METHODS: Participants were 41 males (M age = 18 years) with FXS and co-occurring autism. Interaction samples were coded for expression of predominately 'active' (characterised by a desire to make social approaches) or 'passive' (characterised by lack of initiation of social approach towards others) interaction profiles. Differences in the expression of phenotypic features of FXS, including anxiety, attention-deficit/hyperactivity disorder, cognitive, adaptive and language impairments and autism symptom severity, were examined across those with passive and active interaction styles. RESULTS: Approximately half of the sample was classified as active and half as passive, demonstrating diversity in the social phenotype of autism associated with FXS. The two subtypes did not differ in autism severity, anxiety or attention-deficit/hyperactivity disorder symptoms or in cognitive, adaptive or language abilities. CONCLUSIONS: This study enhances understanding of FXS-associated autism by documenting phenotypic variability in the social interaction profile in this group, with active and passive social interaction styles represented. The two social interaction styles were not associated with differential expression of common phenotypic features of FXS, suggesting similar support needs.

Semi-mechanistic PK/PD modelling of fosfomycin and sulbactam combination against carbapenem-resistant Acinetobacter baumannii.

Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates.Synergism of FOS/SUL against 50 clinical CR-AB isolates were screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill and 2-log kill after 24-hours with combination therapy.The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased four- to eight-fold, compared to the monotherapy MIC50 and MIC90 In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate, at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam 4 g every 8 hours, demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69-76%, as compared to ∼15-30% with monotherapy regimens at the highest doses.The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

"Extremely slow and capricious": A qualitative exploration of genetic researcher priorities in selecting shared data resources.

PURPOSE: Genetic researchers' selection of a database can have scientific, regulatory, and ethical implications. It is important to understand what is driving database selection such that database stewards can be responsive to user needs while balancing the interests of communities in equitably benefiting from advances. METHODS: We conducted 23 semistructured interviews with US academic genetic researchers working with private, government, and collaboratory data stewards to explore factors that they consider when selecting a genetic database. RESULTS: Interviewees used existing databases to avoid burdens of primary data collection, which was described as expensive and time-consuming. They highlighted ease of access as the most important selection factor, integrating concepts of familiarity and efficiency. Data features, such as size and available phenotype, were also important. Demographic diversity was not originally cited by any interviewee as a pivotal factor; when probed, most stated that the option to consider diversity in database selection was limited. Database features, including integrity, harmonization, and storage were also described as key components of efficient use. CONCLUSION: There is a growing market and competition between genetic data stewards. Data need to be accessible, harmonized, and administratively supported for their existence to be translated into use and, in turn, result in scientific advancements across diverse communities.

Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.

The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses.

A Pilot Randomized Trial of a Purposeful and Stimulating Volunteer Opportunity: Program Satisfaction and Potential Impacts on Perceived Cognitive Change in a Neurologically Mixed Sample of Older Adults.

BACKGROUND: Purposeful social interactions are important for healthy aging. We conducted a pilot trial of SPEAK! (Seniors Promoting English Acquisition and Knowledge), an intervention providing older volunteers with a safe, accessible opportunity to converse via webcam with English-language learners. METHODS: A neurologically mixed sample of older adults was randomized to 8 weekly, webcam conversations with English-language learners or a waitlist control. Outcomes included the Cognitive Change Index (CCI) and surveys of program satisfaction. Here, we report on session completion, intervention satisfaction, and follow-up CCI scores. Exploratory analyses of CCI intervention effects controlled for baseline CCI scores and the interaction between group and baseline CCI. RESULTS: Participants (N=38) were on average 70.8 years of age, 28/38 were White, and 16/38 demonstrated possible cognitive impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pairs completed 115/136 sessions (85%) and all volunteers said they would recommend the program. Controlling for the interaction between baseline CCI and randomization group, SPEAK! volunteers had better follow-up CCI scores than controls (P=0.018). Improvements in CCI were greater among participants with fewer baseline memory problems. CONCLUSIONS: SPEAK! was feasible and appreciated by older adults with and without cognitive impairment. Larger studies should confirm benefits for memory and other determinants of quality of life.

Providing a Purposeful and Stimulating Volunteer Opportunity for Older Adults With Mild Cognitive Impairment: A Pilot Study.

Social interactions have cognitive and emotional benefits for older adults with mild cognitive impairment (MCI). The prevalence of loneliness and isolation in this population has been repeatedly noted, but interventions remain limited. We designed a program to connect older adults with MCI with an engaging volunteering opportunity, through videoconferencing conversations with another adult practicing English (English language learner). Ten MCI-English language learner pairs had conversation sessions over 6 weeks. We tracked session engagement, monitored conversations, and interviewed participants at follow-up. Pairs completed 78% of scheduled sessions; only 7% were missed because the MCI participant canceled or failed to appear. Qualitative interviews suggested that participants felt comfortable and engaged. No negative experiences were observed or reported. This program is feasible and potentially desirable for older adults with MCI. This model is interesting given the concern about in-person volunteering risks, and the millions of people motivated to improve English fluency.

Reductions in global biodiversity loss predicted from conservation spending.

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

Integrative clinical genomics of metastatic cancer.

Metastasis is the primary cause of cancer-related deaths. Although The Cancer Genome Atlas has sequenced primary tumour types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here we perform whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair. RNA sequencing complemented DNA sequencing to identify gene fusions, pathway activation, and immune profiling. Our results show that integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of metastatic cancers.

Polyploidy breaks speciation barriers in Australian burrowing frogs Neobatrachus.

Polyploidy has played an important role in evolution across the tree of life but it is still unclear how polyploid lineages may persist after their initial formation. While both common and well-studied in plants, polyploidy is rare in animals and generally less understood. The Australian burrowing frog genus Neobatrachus is comprised of six diploid and three polyploid species and offers a powerful animal polyploid model system. We generated exome-capture sequence data from 87 individuals representing all nine species of Neobatrachus to investigate species-level relationships, the origin and inheritance mode of polyploid species, and the population genomic effects of polyploidy on genus-wide demography. We describe rapid speciation of diploid Neobatrachus species and show that the three independently originated polyploid species have tetrasomic or mixed inheritance. We document higher genetic diversity in tetraploids, resulting from widespread gene flow between the tetraploids, asymmetric inter-ploidy gene flow directed from sympatric diploids to tetraploids, and isolation of diploid species from each other. We also constructed models of ecologically suitable areas for each species to investigate the impact of climate on differing ploidy levels. These models suggest substantial change in suitable areas compared to past climate, which correspond to population genomic estimates of demographic histories. We propose that Neobatrachus diploids may be suffering the early genomic impacts of climate-induced habitat loss, while tetraploids appear to be avoiding this fate, possibly due to widespread gene flow. Finally, we demonstrate that Neobatrachus is an attractive model to study the effects of ploidy on the evolution of adaptation in animals.

The reliability of a portable steam sauna pod for the whole-body passive heating of humans.

INTRODUCTION: Passive heating is receiving increasing attention within human performance and health contexts. A low-cost, portable steam sauna pod may offer an additional tool for those seeking to manipulate physiological (cardiovascular, thermoregulatory and sudomotor) and perceptual responses for improving sporting or health profiles. This study aimed to 1) report the different levels of heat stress and determine the pods' inter-unit reliability, and 2) quantify the reliability of physiological and perceptual responses to passive heating. METHOD: In part 1, five pods were assessed for temperature and relative humidity (RH) every 5 min across 70 min of heating for each of the 9 settings. In part 2, twelve males (age: 24 ± 4 years) completed two 60 min trials of passive heating (3 × 20 min at 44 °C/99% RH, separated by 1 week). Heart rate (HR), rectal (Trectal) and tympanic temperature (Ttympanic) were recorded every 5 min, thermal comfort (Tcomfort) and sensation (Tsensation) every 10 min, mean arterial pressure (MAP) at each break period and sweat rate (SR) after exiting the pod. RESULTS: In part 1, setting 9 provided the highest temperature (44.3 ± 0.2 °C) and longest time RH remained stable at 99% (51±7 min). Inter-unit reliability data demonstrated agreement between pods for settings 5-9 (intra-class correlation [ICC] >0.9), but not for settings 1-4 (ICC <0.9). In part 2, between-visits, high correlations, and low typical error of measurement (TEM) and coefficient of variation (CV) were found for Trectal, HR, MAP, SR, and Tcomfort, but not for Ttympanic or Tsensation. A peak Trectal of 38.09 ± 0.30 °C, HR of 124 ± 15 b min-1 and a sweat loss of 0.73 ± 0.33 L were reported. No between-visit differences (p > 0.05) were observed for Trectal, Ttympanic, Tsensation or Tcomfort, however HR (+3 b.min-1) and MAP (+4 mmHg) were greater in visit 1 vs. 2 (p < 0.05). CONCLUSION: Portable steam sauna pods generate reliable heat stress between-units. The highest setting (44 °C/99% RH) also provides reliable but modest adjustments in physiological and perceptual responses.

A survey of case studies on the use of forensic three-dimensional printing in England and Wales.

3D printing has rapidly developed and been applied in forensic science due to its use in creating demonstrations for courts of law. Much of the literature on this specific topic has focused on the use of 3D printed models in academia, the potential influence on a jury, and its use as a long-term documentation process, but with few actual forensic case examples. This paper offers an insight into the development of 3D printing in forensic practice and how 3D printing is currently being used in the criminal justice system in England and Wales.A series of case reports were gathered from multiple police forces and forensic practitioners in the UK to identify how 3D printing was being used. These discussions established who was requesting 3D printed exhibits, what type of technologies were being utilised, what type of exhibits were being printed, and resulting feedback for the use of 3D printed material within a criminal case. As a result, this research demonstrates the current use of 3D printing in England and Wales, discussing the associated cases that have been known to incorporate 3D prints. Likewise, this work explores the limitations that have been encountered by forensic practitioners and identifies a series of research questions that should be considered in future investigations.

Adolescent and parent perspectives on genomic sequencing to inform cancer care.

Next-generation sequencing offers opportunities for targeted cancer therapies and may identify pathogenic germline variants. Adolescents' perception of testing is not well understood. We surveyed 16 adolescents and 59 parents regarding motivations, attitudes, and knowledge related to paired tumor/germline sequencing. Participants generally had a good objective understanding of germline genetics and cancer risk, with parents scoring higher than adolescents. Nearly all participants were motivated by a desire to help other patients and to treat their child/themselves. Most adolescents reported involvement in the decision to enroll in the study. Study findings suggest important similarities and differences between parent and adolescent views.

Repeated large-scale retreat and advance of Totten Glacier indicated by inland bed erosion.

Climate variations cause ice sheets to retreat and advance, raising or lowering sea level by metres to decametres. The basic relationship is unambiguous, but the timing, magnitude and sources of sea-level change remain unclear; in particular, the contribution of the East Antarctic Ice Sheet (EAIS) is ill defined, restricting our appreciation of potential future change. Several lines of evidence suggest possible collapse of the Totten Glacier into interior basins during past warm periods, most notably the Pliocene epoch, causing several metres of sea-level rise. However, the structure and long-term evolution of the ice sheet in this region have been understood insufficiently to constrain past ice-sheet extents. Here we show that deep ice-sheet erosion-enough to expose basement rocks-has occurred in two regions: the head of the Totten Glacier, within 150 kilometres of today's grounding line; and deep within the Sabrina Subglacial Basin, 350-550 kilometres from this grounding line. Our results, based on ICECAP aerogeophysical data, demarcate the marginal zones of two distinct quasi-stable EAIS configurations, corresponding to the 'modern-scale' ice sheet (with a marginal zone near the present ice-sheet margin) and the retreated ice sheet (with the marginal zone located far inland). The transitional region of 200-250 kilometres in width is less eroded, suggesting shorter-lived exposure to eroding conditions during repeated retreat-advance events, which are probably driven by ocean-forced instabilities. Representative ice-sheet models indicate that the global sea-level increase resulting from retreat in this sector can be up to 0.9 metres in the modern-scale configuration, and exceeds 2 metres in the retreated configuration.

Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour.

The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.

Depot buprenorphine as an opioid agonist therapy in New South Wales correctional centres: a costing model.

BACKGROUND: In 2019 daily liquid methadone and sublingual buprenorphine-naloxone were primary opioid agonist treatments for correctional centres in New South Wales, Australia. However, both had significant potential for diversion to other patients, and their daily administration was resource intensive. An alternative treatment in the form of subcutaneous depot buprenorphine became a viable option following a safety trial in 2020 - the UNLOC-T study. Depot preparation demonstrated advantages over current treatments as more difficult to divert and requiring fewer administrations. This paper reports the results of economic modelling of staffing costs in medication administration comparing depot buprenorphine, methadone, and sublingual buprenorphine provision in UNLOC-T trial facilities. METHODS: The costing study adopted a micro-costing approach involving the synthesis of cost data from the UNLOC-T clinical trial as well as data collected from Justice Health and Forensic Mental Health Network records. Labour and materials data were collected during site observations and interviews. Costs were calculated from two payer perspectives: a) the New South Wales (state) government which funds custodial and health services; and b) the Australian Commonwealth government, which pays for medications. The analysis compared the monthly-per-patient cost for each of the three medications in trial-site facilities during July 2019. This was followed by simulation of depot buprenorphine implementation across the study population. Costs associated with medical assessment and reviews were excluded. RESULTS: The monthly-per-patient New South Wales government service costs of depot buprenorphine, methadone and sublingual buprenorphine were: $151, $379 and $1,529 respectively while Commonwealth government medication costs were $434, $80 and $525. The implementation simulation found that service costs of depot buprenorphine declined as patients transitioned from weekly to monthly administration. Costs of treatment using the other medications increased as patient numbers decreased alongside fixed costs. At 12 months, monthly-per-patient service costs for depot buprenorphine, methadone and sublingual buprenorphine-which would be completely phased out by month 13-were $92, $530 and $2,162 respectively. CONCLUSIONS: Depot buprenorphine was consistently the least costly of the treatment options. Future modelling could allow for dynamic patient populations and downstream impacts for participants and the state health system. TRIAL REGISTRATION: ACTRN12618000942257 . Registered 4 June 2018.

Exploring ecosystem-based management in the North Atlantic.

The United States, the EU and Canada established a trilateral working group on the ecosystem approach to ocean health and stressors under the Atlantic Ocean Research Alliance. Recognizing the Atlantic Ocean as a shared resource and responsibility, the working group sought to advance understanding of the Atlantic Ocean and its dynamic systems to improve ocean health, enhance ocean stewardship and promote the sustainable use and management of its resources. This included consideration of multiple ocean-use sectors such as fishing, shipping, tourism and offshore energy. The working group met for 4 years and worked through eight steps that covered the development of common language as a basis for collaboration, challenges of stakeholder engagement, review of the governance mandates, exploring the links between sectors and ecosystems effects, identifying gaps in knowledge and uptake of science, identification of tools for ecosystem-based management, customary best practice for tool development and communication of key research priorities. The key findings were that ecosystem-based management enables new benefits and opportunities, and that we need to make the business case. Further findings were that adequate mandates and effective tools exist for ecosystem-based management, and that ecosystem-based management urgently requires integration of human dimensions, so we must diversify the conversation. In addition, it was found that stakeholders do not see their stake in ecosystem-based management, so greater engagement with stakeholders and targeting of ocean literacy is required and a sustainable future requires a sustained investment in ecosystem-based management, so long-term commitment is key.