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Background: Aboriginal Community Controlled Health Services (ACCHSs) in Australia aim to optimise access to comprehensive and culturally safe primary health care (PHC) for Aboriginal populations. Central to quality service provision is the retention of staff. However, there is lack of published research reporting patterns of staff turnover and retention specific to ACCHSs. This study quantified staff turnover and retention in regional and remote ACCHSs in the Northern Territory (NT) and Western Australia (WA), and examined correlations between turnover and retention metrics, and ACCHSs' geographical and demographic characteristics., Methods: The study used 2017-2019 payroll data for health workers in 22 regional and remote PHC clinics managed by 11 ACCHSs. Primary outcome measures included annual turnover and 12-month stability rates, calculated at both clinic and organisation levels., Results: There was a median of five client-facing (Aboriginal health practitioners, allied health professionals, doctors, nurses/midwives, and 'other health workers' combined) and two non-client-facing (administrative and physical) staff per remote clinic, at any timepoint. Mean annual turnover rates for staff were very high, with 151% turnover rates at the clinic level and 81% turnover rates at the organisation level. Mean annual turnover rates for client-facing staff were 164% and 75%, compared to 120% and 98% for non-client-facing staff, at clinic and organisational levels, respectively. Mean 12-month stability rates were low, with clinic-level stability rates of only 49% and organisation-level stability rates of 58%. Mean annual clinic-level turnover rates were 162% for non-Aboriginal staff and 81% for Aboriginal staff. Both workforce metrics were moderately to highly correlated with the relative remoteness of clinics, size of regular clients serviced, and average annual headcount of employees in each clinic (p values < 0.01)., Conclusions: Participating ACCHSs in remote NT and WA have very high turnover and low retention of healthcare staff. Overall, clinic-level turnover rates increase as distance from regional centres increases and are lower for Aboriginal staff, suggesting that greater employment of Aboriginal staff could help stabilise staffing. Improved retention could reduce burden on ACCHSs' resources and may also support quality of service delivery due to improved cultural safety and continuity of care., (© 2024. The Author(s).)

Vesicular stomatitis (VS) is a vector-borne livestock disease caused by the vesicular stomatitis New Jersey virus (VSNJV). This study presents the first application of an SEIR-SEI compartmental model to analyze VSNJV transmission dynamics. Focusing on the 2014-2015 outbreak in the United States, the model integrates vertebrate hosts and insect vector demographics while accounting for heterogeneous competency within the populations and observation bias in documented disease cases. Key epidemiological parameters were estimated using Bayesian inference and Markov chain Monte Carlo (MCMC) methods, including the force of infection, effective reproduction number (Rt), and incubation periods. The model revealed significant underreporting, with only 10-24% of infections documented, 23% of which presented with clinical symptoms. These findings underscore the importance of including competence and imperfect detection in disease models to depict outbreak dynamics and inform effective control strategies accurately. As a baseline model, this SEIR-SEI implementation is intended to serve as a foundation for future refinements and expansions to improve our understanding of VS dynamics. Enhanced surveillance and targeted interventions are recommended to manage future VS outbreaks.

We conducted an integrative analysis to elucidate the spatial epidemiological patterns of the Vesicular Stomatitis New Jersey virus (VSNJV) during the 2014-15 epizootic cycle in the United States (US). Using georeferenced VSNJV genomics data, confirmed vesicular stomatitis (VS) disease cases from surveillance, and a suite of environmental factors, our study assessed environmental and phylogenetic similarity to compare VS cases reported in 2014 and 2015. Despite uncertainties from incomplete virus sampling and cross-scale spatial processes, patterns suggested multiple independent re-invasion events concurrent with potential viral overwintering between sequential seasons. Our findings pointed to a geographically defined southern virus pool at the US-Mexico interface as the source of VSNJV invasions and overwintering sites. Phylodynamic analysis demonstrated an increase in virus diversity before a rise in case numbers and a pronounced reduction in virus diversity during the winter season, indicative of a genetic bottleneck and a significant narrowing of virus variation between the summer outbreak seasons. Environment-vector interactions underscored the central role of meta-population dynamics in driving disease spread. These insights emphasize the necessity for location- and time-specific management practices, including rapid response, movement restrictions, vector control, and other targeted interventions.

Introduction: The COVID-19 pandemic period (2020 to 2022) challenged and overstretched the capacity of primary health care services to deliver health care globally. The sector faced a highly uncertain and dynamic period that encompassed anticipation of a new, unknown, lethal and highly transmissible infection, the introduction of various travel restrictions, health workforce shortages, new government funding announcements and various policies to restrict the spread of the COVID-19 virus, then vaccination and treatments. This qualitative study aims to document and explore how the pandemic affected primary health care utilisation and delivery in remote and regional Aboriginal and Torres Strait Islander communities., Methods: Semi-structured interviews were conducted with staff working in 11 Aboriginal Community-Controlled Health Services (ACCHSs) in outer regional, remote and very remote Australia. Interviews were transcribed, inductively coded and thematically analysed., Results: 248 staff working in outer regional, remote and very remote primary health care clinics were interviewed between February 2020 and June 2021. Participants reported a decline in numbers of primary health care presentations in most communities during the initial COVID-19 lock down period. The reasons for the decline were attributed to community members apprehension to go to the clinics, change in work priorities of primary health care staff (e.g. more emphasis on preventing the virus entering the communities and stopping the spread) and limited outreach programs. Staff forecasted a future spike in acute presentations of various chronic diseases leading to increased medical retrieval requirements from remote communities to hospital. Information dissemination during the pre-vaccine roll-out stage was perceived to be well received by community members, while vaccine roll-out stage information was challenged by misinformation circulated through social media., Conclusions: The ability of ACCHSs to be able to adapt service delivery in response to the changing COVID-19 strategies and policies are highlighted in this study. The study signifies the need to adequately fund ACCHSs with staff, resources, space and appropriate information to enable them to connect with their communities and continue their work especially in an era where the additional challenges created by pandemics are likely to become more frequent. While the PHC seeking behaviour of community members during the COVID-19 period were aligned to the trends observed across the world, some of the reasons underlying the trends were unique to outer regional, remote and very remote populations. Policy makers will need to give due consideration to the potential effects of newly developed policies on ACCHSs operating in remote and regional contexts that already battle under resourcing issues and high numbers of chronically ill populations., (© 2024. The Author(s).)

In recent years, there has been an increasing trend of short-term staffing in remote health services, including Aboriginal Community-Controlled Health Services (ACCHSs). This paper explores the perceptions of clinic users' experiences at their local clinic and how short-term staffing impacts the quality of service, acceptability, cultural safety, and continuity of care in ACCHSs in remote communities. Using purposeful and convenience sampling, community users (aged 18+) of the eleven partnering ACCHSs were invited to provide feedback about their experiences through an interview or focus group. Between February 2020 and October 2021, 331 participants from the Northern Territory and Western Australia were recruited to participate in the study. Audio recordings were transcribed verbatim, and written notes and transcriptions were analysed deductively. Overall, community users felt that their ACCHS provided comprehensive healthcare that was responsive to their health needs and was delivered by well-trained staff. In general, community users expressed concern over the high turnover of staff. Recognising the challenges of attracting and retaining staff in remote Australia, community users were accepting of rotation and job-sharing arrangements, whereby staff return periodically to the same community, as this facilitated trusting relationships. Increased support for local employment pathways, the use of interpreters to enhance communication with healthcare services, and services for men delivered by men were priorities for clinic users.

Previous study has demonstrated that the WNK kinases 1 and 3 are direct osmosensors consistent with their established role in cell-volume control. WNK kinases may also be regulated by hydrostatic pressure. Hydrostatic pressure applied to cells in culture with N 2 gas or to Drosophila Malpighian tubules by centrifugation induces phosphorylation of downstream effectors of endogenous WNKs. In vitro, the autophosphorylation and activity of the unphosphorylated kinase domain of WNK3 (uWNK3) is enhanced to a lesser extent than in cells by 190 kPa applied with N 2 gas. Hydrostatic pressure measurably alters the structure of uWNK3. Data from size exclusion chromatography in line with multi-angle light scattering (SEC-MALS), SEC alone at different back pressures, analytical ultracentrifugation (AUC), NMR, and chemical crosslinking indicate a change in oligomeric structure in the presence of hydrostatic pressure from a WNK3 dimer to a monomer. The effects on the structure are related to those seen with osmolytes. Potential mechanisms of hydrostatic pressure activation of uWNK3 and the relationships of pressure activation to WNK osmosensing are discussed.

Background: Previous studies undertaken in New Zealand using generic rurality classifications have concluded that life expectancy and age-standardised mortality rates are similar for urban and rural populations., Methods: Administrative mortality (2014-2018) and census data (2013 and 2018) were used to estimate age-stratified sex-adjusted mortality rate ratios (aMRRs) for a range of mortality outcomes across the rural-urban spectrum (using major urban centres as the reference) for the total population and separately for Māori and non-Māori. Rural was defined according to the recently developed Geographic Classification for Health., Results: Mortality rates were higher overall in rural areas. This was most pronounced in the youngest age group (<30 years) in the most remote communities (eg, all-cause, amenable and injury-related aMRRs (95% CIs) were 2.1 (1.7 to 2.6), 2.5 (1.9 to 3.2) and 3.0 (2.3 to 3.9) respectively. The rural:urban differences attenuated markedly with increasing age; for some outcomes in those aged 75 years or more, estimated aMRRs were <1.0. Similar patterns were observed for Māori and non-Māori., Conclusion: This is the first time that a consistent pattern of higher mortality rates for rural populations has been observed in New Zealand. A purpose-built urban-rural classification and age stratification were important factors in unmasking these disparities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Climate change and habitat loss are recognized as important drivers of shifts in wildlife species' geographic distributions. While often considered independently, there is considerable overlap between these drivers, and understanding how they contribute to range shifts can predict future species assemblages and inform effective management. Our objective was to evaluate the impacts of habitat, climatic, and anthropogenic effects on the distributions of climate-sensitive vertebrates along a southern range boundary in Northern Michigan, USA. We combined multiple sources of occurrence data, including harvest and citizen-science data, then used hierarchical Bayesian spatial models to determine habitat and climatic associations for four climate-sensitive vertebrate species (American marten [ Martes americana ], snowshoe hare [ Lepus americanus ], ruffed grouse [ Bonasa umbellus ] and moose [ Alces alces ]). We used total basal area of at-risk forest types to represent habitat, and temperature and winter habitat indices to represent climate. Marten associated with upland spruce-fir and lowland riparian forest types, hares with lowland conifer and aspen-birch, grouse with lowland riparian hardwoods, and moose with upland spruce-fir. Species differed in climatic drivers with hares positively associated with cooler annual temperatures, moose with cooler summer temperatures and grouse with colder winter temperatures. Contrary to expectations, temperature variables outperformed winter habitat indices. Model performance varied greatly among species, as did predicted distributions along the southern edge of the Northwoods region. As multiple species were associated with lowland riparian and upland spruce-fir habitats, these results provide potential for efficient prioritization of habitat management. Both direct and indirect effects from climate change are likely to impact the distribution of climate-sensitive species in the future and the use of multiple data types and sources in the modelling of species distributions can result in more accurate predictions resulting in improved management at policy-relevant scales., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: The COVID-19 pandemic increased the use of telehealth consultations by telephone and video around the world. While telehealth can improve access to primary health care, there are significant gaps in our understanding about how, when and to what extent telehealth should be used. This paper explores the perspectives of health care staff on the key elements relating to the effective use of telehealth for patients living in remote Australia., Methods: Between February 2020 and October 2021, interviews and discussion groups were conducted with 248 clinic staff from 20 different remote communities across northern Australia. Interview coding followed an inductive approach. Thematic analysis was used to group codes into common themes., Results: Reduced need to travel for telehealth consultations was perceived to benefit both health providers and patients. Telehealth functioned best when there was a pre-established relationship between the patient and the health care provider and with patients who had good knowledge of their personal health, spoke English and had access to and familiarity with digital technology. On the other hand, telehealth was thought to be resource intensive, increasing remote clinic staff workload as most patients needed clinic staff to facilitate the telehealth session and complete background administrative work to support the consultation and an interpreter for translation services. Clinic staff universally emphasised that telehealth is a useful supplementary tool, and not a stand-alone service model replacing face-to-face interactions., Conclusion: Telehealth has the potential to improve access to healthcare in remote areas if complemented with adequate face-to-face services. Careful workforce planning is required while introducing telehealth into clinics that already face high staff shortages. Digital infrastructure with reliable internet connections with sufficient speed and latency need to be available at affordable prices in remote communities to make full use of telehealth consultations. Training and employment of local Aboriginal staff as digital navigators could ensure a culturally safe clinical environment for telehealth consultations and promote the effective use of telehealth services among community members., (© 2023. The Author(s).)

Introduction: WNK [with no lysine (K)] kinases are serine/threonine kinases associated with familial hyperkalemic hypertension (FHHt). WNKs are therapeutic targets for blood pressure regulation, stroke and several cancers including triple negative breast cancer and glioblastoma. Here, we searched for and characterized novel WNK kinase inhibitors., Methods: We used a ~210,000-compound library in a high-throughput screen, re-acquisition and assay, commercial specificity screens and crystallography to identify WNK-isoform-selective inhibitors., Results: We identified five classes of compounds that inhibit the kinase activity of WNK1: quinoline compounds, halo-sulfones, cyclopropane-containing thiazoles, piperazine-containing compounds, and nitrophenol-derived compounds. The compounds are strongly pan-WNK selective, inhibiting all four WNK isoforms. A class of quinoline compounds was identified that further shows selectivity among the WNK isoforms, being more potent toward WNK3 than WNK1. The crystal structure of the quinoline-derived SW120619 bound to the kinase domain of WNK3 reveals active site binding, and comparison to the WNK1 structure reveals the potential origin of isoform specificity., Discussion: The newly discovered classes of compounds may be starting points for generating pharmacological tools and potential drugs treating hypertension and cancer., Competing Interests: All authors report no conflicts of interest in this work., (© 2023 Chlebowicz et al.)

Background: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement., Methods: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill., Results: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill., Conclusions: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases)., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.

Ammonia is a natural pollutant in wastewater and removal technique such as ammonia electro-oxidation is of paramount importance. The development of highly efficient and low-costing electrocatalysts for the ammonia oxidation reaction (AOR) and hydrogen evolution reaction (HER) associated with ammonia removal is subsequently crucial. In this study, for the first time, the authors demonstrate that a perovskite oxide LaNi 0.5 Cu 0.5 O 3-δ after being annealed in Ar (LNCO55-Ar), is an excellent non-noble bifunctional catalyst towards both AOR and HER, making it suitable as a symmetric ammonia electrolyser (SAE) in alkaline medium. In contrast, the LNCO55 sample fired in air (LNCO55-Air) is inactive towards AOR and shows very poor HER activity. Through combined experimental results and theoretical calculations, it is found that the superior AOR and HER activities are attributed to the increased active sites, the introduction of oxygen vacancies, the synergistic effect of B-site cations and the different active sites in LNCO55-Ar. At 1.23 V, the assembled SAE demonstrates ≈100% removal efficiency in 2210 ppm ammonia solution and >70% in real landfill leachate. This work opens the door for developments towards bifunctional catalysts, and also takes a profound step towards the development of low-costing and simple device configuration for ammonia electrolysers., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objectives: To evaluate the relationship between markers of staff employment stability and use of short-term healthcare workers with markers of quality of care. A secondary objective was to identify clinic-specific factors which may counter hypothesised reduced quality of care associated with lower stability, higher turnover or higher use of short-term staff., Design: Retrospective cohort study (Northern Territory (NT) Department of Health Primary Care Information Systems)., Setting: All 48 government primary healthcare clinics in remote communities in NT, Australia (2011-2015)., Participants: 25 413 patients drawn from participating clinics during the study period., Outcome Measures: Associations between independent variables (resident remote area nurse and Aboriginal Health Practitioner turnover rates, stability rates and the proportional use of agency nurses) and indicators of health service quality in child and maternal health, chronic disease management and preventive health activity were tested using linear regression, adjusting for community and clinic size. Latent class modelling was used to investigate between-clinic heterogeneity., Results: The proportion of resident Aboriginal clients receiving high-quality care as measured by various quality indicators varied considerably across indicators and clinics. Higher quality care was more likely to be received for management of chronic diseases such as diabetes and least likely to be received for general/preventive adult health checks. Many indicators had target goals of 0.80 which were mostly not achieved. The evidence for associations between decreased stability measures or increased use of agency nurses and reduced achievement of quality indicators was not supported as hypothesised. For the majority of associations, the overall effect sizes were small (close to zero) and failed to reach statistical significance. Where statistically significant associations were found, they were generally in the hypothesised direction., Conclusions: Overall, minimal evidence of the hypothesised negative effects of increased turnover, decreased stability and increased reliance on temporary staff on quality of care was found. Substantial variations in clinic-specific estimates of association were evident, suggesting that clinic-specific factors may counter any potential negative effects of decreased staff employment stability. Investigation of clinic-specific factors using latent class analysis failed to yield clinic characteristics that adequately explain between-clinic variation in associations. Understanding the reasons for this variation would significantly aid the provision of clinical care in remote Australia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

N , N -Dimethylacetamide (DMA) cooperated with LiNO 3 salt has previously shown to be a promising electrolyte for a Li//O 2 battery, showing good stability against both the O 2 electrode reaction and Li stripping/plating. In this work, DMA is hybridized with a concentrated nitrate electrolyte [2.5 m Zn(NO 3 ) 2 + 13 m LiNO 3 aqueous solution] for better electrochemical stability while using less dissolved salts. The widest electrochemical stability window for this DMA-diluted electrolyte is determined as 3.1 V, the negative critical stability potential of which is -1.6 V versus Ag/AgCl, indicating desirable stability against hydrogen evolution and Zn deposition. The findings can be attributed to the weakened Li + /Zn 2+ solvation sheath caused by low permittivity of DMA, as revealed through Raman spectra characterization and molecular dynamics simulation. A Zn//Zn symmetrical cell and Zn//LiMn 2 O 4 hybrid ion batteries are assembled in air directly, attributed to the stability of DMA toward O 2 . Zn stripping/plating with a dendrite-free morphology is delivered for 110 h and 200 charge/discharge cycles under 1 C rate, achieving 99.0% Coulombic efficiency. The maximum capacity of the battery is 121.0 mA h·g -1 under 0.2 C rate (based on the mass of LiMn 2 O 4 ), delivering an energy density of 165.8 W h·kg -1 together with 2.0 V working voltage. This work demonstrates the feasibility and validity of utilizing a relatively dilute electrolyte dissolved in oxygen for a highly stable aqueous rechargeable battery.

Mosquito-borne West Nile virus (WNV) is the causative agent of West Nile disease in humans, horses, and some bird species. Since the initial introduction of WNV to the United States (US), approximately 30,000 horses have been impacted by West Nile neurologic disease and hundreds of additional horses are infected each year. Research describing the drivers of West Nile disease in horses is greatly needed to better anticipate the spatial and temporal extent of disease risk, improve disease surveillance, and alleviate future economic impacts to the equine industry and private horse owners. To help meet this need, we integrated techniques from spatiotemporal epidemiology, eco-phylogenetics, and distributional ecology to assess West Nile disease risk in horses throughout the contiguous US. Our integrated approach considered horse abundance and virus exposure, vector and host distributions, and a variety of extrinsic climatic, socio-economic, and environmental risk factors. Birds are WNV reservoir hosts, and therefore we quantified avian host community dynamics across the continental US to show intra-annual variability in host phylogenetic structure and demonstrate host phylodiversity as a mechanism for virus amplification in time and virus dilution in space. We identified drought as a potential amplifier of virus transmission and demonstrated the importance of accounting for spatial non-stationarity when quantifying interaction between disease risk and meteorological influences such as temperature and precipitation. Our results delineated the timing and location of several areas at high risk of West Nile disease and can be used to prioritize vaccination programs and optimize virus surveillance and monitoring.

Background: Attracting and retaining sufficient health workers to provide adequate services for residents of rural and remote areas has global significance. High income countries (HICs) face challenges in staffing rural areas, which are often perceived by health workers as less attractive workplaces. The objective of this review was to examine the quantifiable associations between interventions to retain health workers in rural and remote areas of HICs, and workforce retention., Methods: The review considers studies of rural or remote health workers in HICs where participants have experienced interventions, support measures or incentive programs intended to increase retention. Experimental, quasi-experimental and observational study designs including cohort, case-control, cross-sectional and case series studies published since 2010 were eligible for inclusion. The Joanna Briggs Institute methodology for reviews of risk and aetiology was used. Databases searched included MEDLINE (OVID), CINAHL (EBSCO), Embase, Web of Science and Informit., Results: Of 2649 identified articles, 34 were included, with a total of 58,188 participants. All study designs were observational, limiting certainty of findings. Evidence relating to the retention of non-medical health professionals was scant. There is growing evidence that preferential selection of students who grew up in a rural area is associated with increased rural retention. Undertaking substantial lengths of rural training during basic university training or during post-graduate training were each associated with higher rural retention, as was supporting existing rural health professionals to extend their skills or upgrade their qualifications. Regulatory interventions requiring return-of-service (ROS) in a rural area in exchange for visa waivers, access to professional licenses or provider numbers were associated with comparatively low rural retention, especially once the ROS period was complete. Rural retention was higher if ROS was in exchange for loan repayments., Conclusion: Educational interventions such as preferential selection of rural students and distributed training in rural areas are associated with increased rural retention of health professionals. Strongly coercive interventions are associated with comparatively lower rural retention than interventions that involve less coercion. Policy makers seeking rural retention in the medium and longer term would be prudent to strengthen rural training pathways and limit the use of strongly coercive interventions., (© 2021. The Author(s).)

With No Lysine (K) WNK kinases regulate electro-neutral cotransporters that are controlled by osmotic stress and chloride. We showed previously that autophosphorylation of WNK1 is inhibited by chloride, raising the possibility that WNKs are activated by osmotic stress. Here we demonstrate that unphosphorylated WNK isoforms 3 and 1 autophosphorylate in response to osmotic pressure in vitro, applied with the crowding agent polyethylene glycol (PEG)400 or osmolyte ethylene glycol (EG), and that this activation is opposed by chloride. Small angle x-ray scattering of WNK3 in the presence and absence of PEG400, static light scattering in EG, and crystallography of WNK1 were used to understand the mechanism. Osmosensing in WNK3 and WNK1 appears to occur through a conformational equilibrium between an inactive, unphosphorylated, chloride-binding dimer and an autophosphorylation-competent monomer. An improved structure of the inactive kinase domain of WNK1, and a comparison with the structure of a monophosphorylated form of WNK1, suggests that large cavities, greater hydration, and specific bound water may participate in the osmosensing mechanism. Our prior work showed that osmolytes have effects on the structure of phosphorylated WNK1, suggestive of multiple stages of osmotic regulation in WNKs.

Introduction: Access to high-quality primary healthcare is limited for remote residents in Australia. Increasingly, remote health services are reliant on short-term or 'fly-in, fly-out/drive-in, drive-out' health workforce to deliver primary healthcare. A key strategy to achieving health service access equity, particularly evident in remote Australia, has been the development of Aboriginal Community Controlled Health Services (ACCHSs). This study aims to generate new knowledge about (1) the impact of short-term staffing in remote and rural ACCHSs on Aboriginal and Torres Strait Islander communities; (2) the potential mitigating effect of community control; and (3) effective, context-specific evidence-based retention strategies., Methods and Analysis: This paper describes a 3-year, mixed methods study involving 12 ACCHSs across three states. The methods are situated within an evidence-based programme logic framework for rural and remote primary healthcare services. Quantitative data will be used to describe staffing stability and turnover, with multiple regression analyses to determine associations between independent variables (population size, geographical remoteness, resident staff turnover and socioeconomic status) and dependent variables related to patient care, service cost, quality and effectiveness. Qualitative assessment will include interviews and focus groups with clinical staff, clinic users, regionally-based retrieval staff and representatives of jurisdictional peak bodies for the ACCHS sector, to understand the impact of short-term staff on quality and continuity of patient care, as well as satisfaction and acceptability of services., Ethics and Dissemination: The study has ethics approval from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (project number DR03171), Central Australian Human Research Ethics Committee (CA-19-3493), Western Australian Aboriginal Health Ethics Committee (WAAHEC-938) and Far North Queensland Human Research Ethics Committee (HREC/2019/QCH/56393). Results will be disseminated through peer-reviewed journals, the project steering committee and community/stakeholder engagement activities to be determined by each ACCHS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Vesicular stomatitis (VS) is a vector-borne livestock disease caused by vesicular stomatitis New Jersey virus (VSNJV) or vesicular stomatitis Indiana virus (VSIV). The disease circulates endemically in northern South America, Central America, and Mexico and only occasionally causes outbreaks in the United States. Over the past 20 years, VSNJV outbreaks in the southwestern and Rocky Mountain regions occurred with incursion years followed by virus overwintering and subsequent expansion outbreak years. Regulatory response by animal health officials is deployed to prevent spread from lesioned animals. The 2019 VS incursion was the largest in 40 years, lasting from June to December 2019 with 1144 VS-affected premises in 111 counties in eight states (Colorado, Kansas, Nebraska, New Mexico, Oklahoma, Texas, Utah, and Wyoming) and was VSIV serotype, last isolated in 1998. A subsequent expansion occurred from April to October 2020 with 326 VS-affected premises in 70 counties in eight states (Arizona, Arkansas, Kansas, Missouri, Nebraska, New Mexico, Oklahoma, and Texas). The primary serotype in 2020 was VSIV, but a separate incursion of VSNJV occurred in south Texas. Summary characteristics of the outbreaks are presented along with VSV-vector sampling results and phylogenetic analysis of VSIV isolates providing evidence of virus overwintering.

West Nile virus (WNV) is the most common arthropod-borne virus (arbovirus) in the United States (US) and is the leading cause of viral encephalitis in the country. The virus has affected tens of thousands of US persons total since its 1999 North America introduction, with thousands of new infections reported annually. Approximately 1% of humans infected with WNV acquire neuroinvasive West Nile Disease (WND) with severe encephalitis and risk of death. Research describing WNV ecology is needed to improve public health surveillance, monitoring, and risk assessment. We applied Bayesian joint-spatiotemporal modeling to assess the association of vector surveillance data, host species richness, and a variety of other environmental and socioeconomic disease risk factors with neuroinvasive WND throughout the conterminous US. Our research revealed that an aging human population was the strongest disease indicator, but climatic and vector-host biotic interactions were also significant in determining risk of neuroinvasive WND. Our analysis also identified a geographic region of disproportionately high neuroinvasive WND disease risk that parallels the Continental Divide, and extends southward from the US-Canada border in the states of Montana, North Dakota, and Wisconsin to the US-Mexico border in western Texas. Our results aid in unraveling complex WNV ecology and can be applied to prioritize disease surveillance locations and risk assessment.

With no lysine (K) (WNK) kinases regulate epithelial ion transport in the kidney to maintain homeostasis of electrolyte concentrations and blood pressure. Chloride ion directly binds WNK kinases to inhibit autophosphorylation and activation. Changes in extracellular potassium are thought to regulate WNKs through changes in intracellular chloride. Prior studies demonstrate that in some distal nephron epithelial cells, intracellular potassium changes with chronic low- or high-potassium diet. We, therefore, investigated whether potassium regulates WNK activity independent of chloride. We found decreased activity of Drosophila WNK and mammalian WNK3 and WNK4 in fly Malpighian (renal) tubules bathed in high extracellular potassium, even when intracellular chloride was kept constant at either ∼13 mM or 26 mM. High extracellular potassium also inhibited chloride-insensitive mutants of WNK3 and WNK4. High extracellular rubidium was also inhibitory and increased tubule rubidium. The Na + /K + -ATPase inhibitor, ouabain, which is expected to lower intracellular potassium, increased tubule Drosophila WNK activity. In vitro, potassium increased the melting temperature of Drosophila WNK, WNK1, and WNK3 kinase domains, indicating ion binding to the kinase. Potassium inhibited in vitro autophosphorylation of Drosophila WNK and WNK3, and also inhibited WNK3 and WNK4 phosphorylation of their substrate, Ste20-related proline/alanine-rich kinase (SPAK). The greatest sensitivity of WNK4 to potassium occurred in the range of 80-180 mM, encompassing physiological intracellular potassium concentrations. Together, these data indicate chloride-independent potassium inhibition of Drosophila and mammalian WNK kinases through direct effects of potassium ion on the kinase.

WNK kinases autoactivate by autophosphorylation. Crystallography of the kinase domain of WNK1 phosphorylated on the primary activating site (pWNK1) in the presence of AMP-PNP reveals a well-ordered but inactive configuration. This new pWNK1 structure features specific and unique interactions of the phosphoserine, less hydration, and smaller cavities compared with those of unphosphorylated WNK1 (uWNK1). Because WNKs are activated by osmotic stress in cells, we addressed whether the structure was influenced directly by osmotic pressure. pWNK1 crystals formed in PEG3350 were soaked in the osmolyte sucrose. Suc-WNK1 crystals maintained X-ray diffraction, but the lattice constants and pWNK1 structure changed. Differences were found in the activation loop and helix C, common switch loci in kinase activation. On the basis of these structural changes, we tested for effects on in vitro activity of two WNKs, pWNK1 and pWNK3. The osmolyte PEG400 enhanced ATPase activity. Our data suggest multistage activation of WNKs.

Avian influenza (AI) affects wild aquatic birds and poses hazards to human health, food security, and wildlife conservation globally. Accordingly, there is a recognized need for new methods and tools to help quantify the dynamic interaction between wild bird hosts and commercial poultry. Using satellite-marked waterfowl, we applied Bayesian joint hierarchical modeling to concurrently model species distributions, residency times, migration timing, and disease occurrence probability under an integrated animal movement and disease distribution modeling framework. Our results indicate that migratory waterfowl are positively related to AI occurrence over North America such that as waterfowl occurrence probability or residence time increase at a given location, so too does the chance of a commercial poultry AI outbreak. Analyses also suggest that AI occurrence probability is greatest during our observed waterfowl northward migration, and less during the southward migration. Methodologically, we found that when modeling disparate facets of disease systems at the wildlife-agriculture interface, it is essential that multiscale spatial patterns be addressed to avoid mistakenly inferring a disease process or disease-environment relationship from a pattern evaluated at the improper spatial scale. The study offers important insights into migratory waterfowl ecology and AI disease dynamics that aid in better preparing for future outbreaks.

Objectives: To establish the acceptability and feasibility of collecting daily patient-generated health data (PGHD) using smartphones and integrating PGHD into the electronic health record, using the example of RA., Methods: The Remote Monitoring of RA smartphone app was co-designed with patients, clinicians and researchers using qualitative semi-structured interviews and focus groups, including selection of question sets for symptoms and disease impact. PGHD were integrated into the electronic health record of one hospital and available in graphical form during consultations. Acceptability and feasibility were assessed with 20 RA patients and two clinicians over 3 months. A qualitative evaluation included semi-structured interviews with patients and clinicians before and after using the app, and audio-recordings of consultations to explore impact on the consultation. PGHD completeness was summarized descriptively, and qualitative data were analysed thematically., Results: Patients submitted data on a median of 91% days over 3 months. Qualitative analysis generated three themes: RA as an invisible disease; providing the bigger picture of RA; and enabling person-centred consultations. The themes demonstrated that the system helped render patients' RA more visible by providing the 'bigger picture', identifying real-time changes in disease activity and capturing symptoms that would otherwise have been missed. Graphical summaries during consultations enabled a more person-centred approach whereby patients felt better able to participate in consultations and treatment plans., Conclusion: Remote Monitoring of RA has uniquely integrated daily PGHD from smartphones into the electronic health record. It has delivered proof-of-concept that such integrated remote monitoring systems are feasible and can transform consultations for clinician and patient benefit., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: The objective of the current review is to examine the association between exposure to strategies or interventions to retain health workers in rural and remote areas of high-income countries and improved retention rates., Introduction: Attracting and retaining sufficient healthcare staff to provide adequate services for residents of rural and remote areas is an international problem. High-income countries have specific challenges in staffing remote and rural areas; despite the majority of the population clustering in large cities, a significant number of communities are in rural, remote or frontier areas which may be perceived as less attractive locations in which to live and work., Inclusion Criteria: The review will consider studies that include health workers in high-income countries where participants have been exposed to interventions, support measures or incentive programs to increase retention or workforce length of employment or reduce turnover for health workers in rural and remote areas. Analytical observational studies, case-control studies, analytical cross-sectional studies, descriptive observational study designs, and descriptive cross-sectional studies published from 2010 will be eligible for inclusion., Methods: We will use the JBI methodology for reviews of risk and etiology. A range of databases will be searched. Two reviewers will screen, critically appraise eligible articles, and extract data from included studies. Data synthesis will be conducted, where feasible, with RevMan 5.3.5. A random effects model will be used to conduct meta-analyses. We will assess the certainty of the findings using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Background: Residents of remote communities in Australia and other geographically large countries have comparatively poorer access to high-quality primary health care. To inform ongoing policy development and practice in relation to remote area health service delivery, particularly in remote Indigenous communities, this review synthesizes the key findings of (1) a comprehensive study of workforce turnover and retention in remote Northern Territory (NT) of Australia and (2) a narrative review of relevant international literature on remote and rural health workforce retention strategies. This synthesis provides a valuable summary of the current state of international knowledge about improving remote health workforce retention., Main Text: Annual turnover rates of NT remote area nurses (148%) and Aboriginal health practitioners (80%) are very high and 12-month stability rates low (48% and 76%, respectively). In remote NT, use of agency nurses has increased substantially. Primary care costs are high and proportional to staff turnover and remoteness. Effectiveness of care decreases with higher turnover and use of short-term staff, such that higher staff turnover is always less cost-effective. If staff turnover in remote clinics were halved, the potential savings would be approximately A$32 million per annum. Staff turnover and retention were affected by management style and effectiveness, and employment of Indigenous staff. Review of the international literature reveals three broad themes: Targeted enrolment into training and appropriate education designed to produce a competent, accessible, acceptable and 'fit-for-purpose' workforce; addressing broader health system issues that ensure a safe and supportive work environment; and providing ongoing individual and family support. Key educational initiatives include prioritising remote origin and Indigenous students for university entry; maximising training in remote areas; contextualising curricula; providing financial, pedagogical and pastoral support; and ensuring clear, supported career pathways and continuing professional development. Health system initiatives include ensuring adequate funding; providing adequate infrastructure including fit-for-purpose clinics, housing, transport and information technology; offering flexible employment arrangements whilst ensuring a good 'fit' between individual staff and the community (especially with regard to cultural skills); optimising co-ordination and management of services that empower staff and create positive practice environments; and prioritising community participation and employment of locals. Individual and family supports include offering tailored financial incentives, psychological support and 'time out'., Conclusion: Optimal remote health workforce stability and preventing excessive 'avoidable' turnover mandates alignment of government and health authority policies with both health service requirements and individual health professional and community needs. Supportive underpinning policies include: Strong intersectoral collaboration between the health and education sectors to ensure a fit-for-purpose workforce;A funding policy which mandates the development and implementation of an equitable, needs-based formula for funding remote health services;Policies that facilitate transition to community control, prioritise Indigenous training and employment, and mandate a culturally safe work context; andAn employment policy which provides flexibility of employment conditions in order to be able to offer individually customised retention packages There is considerable extant evidence from around the world about effective retention strategies that contribute to slowing excessive remote health workforce turnover, resulting in significant cost savings and improved continuity of care. The immediate problem comprises an 'implementation gap' in translating empirical research evidence into actions designed to resolve existing problems. If we wish to ameliorate the very high turnover of staff in remote areas, in order to provide an equitable service to populations with arguably the highest health needs, we need political and executive commitment to get the policy settings right and ensure the coordinated implementation of multiple strategies, including better linking existing strategies and 'filling the gaps' where necessary.

Objectives: To compare the costs and effects of higher turnover of resident nurses and Aboriginal health practitioners and higher use of agency-employed nurses in remote primary care (PC) services and quantify associations between staffing patterns and health outcomes in remote PC clinics in the Northern Territory (NT) of Australia., Design: Observational cohort study, using hospital admission, financial and payroll data for the period 2013-2015., Setting: 53 NT Government run PC clinics in remote communities., Outcome Measures: Incremental cost-effectiveness ratios were calculated for higher compared with lower turnover and higher compared with lower use of agency-employed nurses. Costs comprised PC, travel and hospitalisation costs. Effect measures were total hospitalisations and years of life lost per 1000 person-months. Multiple regression was performed to investigate associations between overall health costs and turnover rates and use of agency-employed nurses, after adjusting for key confounders., Results: Higher turnover was associated with significantly higher hospitalisation rates (p<0.001) and higher average health costs (p=0.002) than lower turnover. Lower turnover was always more cost-effective. Average costs were significantly (p<0.001) higher when higher proportions of agency-employed nurses were employed. The probability that lower use of agency-employed nurses was more cost-effective was 0.84. Halving turnover and reducing use of a short-term workforce have the potential to save $32 million annually in the NT., Conclusion: High turnover of health staff is costly and associated with poorer health outcomes for Aboriginal peoples living in remote communities. High reliance on agency nurses is also very likely to be cost- ineffective . Investment in a coordinated range of workforce strategies that support recruitment and retention of resident nurses and Aboriginal health practitioners in remote clinics is needed to stabilise the workforce, minimise the risks of high staff turnover and over-reliance on agency nurses and thereby significantly reduce expenditure and improve health outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives The aim of this study was to estimate the costs of providing primary care and quantify the cost impact of high staff turnover in Northern Territory (NT) remote communities. Methods This cost impact assessment used administrative data from NT Department of Health datasets, including the government accounting system and personnel information and payroll systems between 2004 and 2015, and the primary care information system from 2007 to 2015. Data related to 54 government-managed clinics providing primary care for approximately 27200 Aboriginal and non-Aboriginal people. Main outcome measures were average costs per consultation and per capita, cost differentials by clinic, year and levels of staff turnover. Linear regression and dominance analysis were used to assess the effect of staff turnover on primary care costs, after adjusting for remoteness and weighting analysis by service population. Both current and constant prices were used. Results On average, in constant prices, there was a nearly 10% annual increase in remote clinic expenditure between 2004 and 2015 and an almost 15% annual increase in consultation numbers since 2007. In real terms, the average costs per consultation decreased markedly from A$273 in 2007 to A$197 in 2015, a figure still well above the Medicare bulk-billing rate. The cost differentials between clinics were proportional to staff turnover and remoteness (both P<0.001). A 10% higher annual turnover rate pertains to an A$6.12 increase in costs per consultation. Conclusions High staff turnover exacerbates the already high costs of providing primary care in remote areas, costing approximately A$50 extra per consultation. This equates to an extra A$400000 per clinic per year on average, or A$21million annually for the NT government. Over time, sustained investments in developing a more stable primary care workforce should not only improve primary care in remote areas, but also reduce the costs of excessive turnover and overall service delivery costs. What is known about the topic? Population size and geographical remoteness are important cost drivers in remote clinics, whereas elsewhere in Australia the high use of short-term staff to fill positions has been identified as a major contributor to higher nurse turnover costs and to overall health service costs. Nursing staff expenditure accounts for a large proportion (46%) of total expenditure in NT remote health services, whereas expenditure on Aboriginal Health Practitioners (AHPs) comprises only 6%. Annual nurse turnover rates in remote NT clinics average approximately 150%, whereas levels of 40% in other contexts are considered high. What does this paper add? Annual expenditure for NT remote clinics has increased, on average, by 10% per annum between 2004 and 2015, but small declines in real expenditure have been observed from a maximum in 2012. Expenditure on nursing staff comprises 40% of overall expenditure in remote clinics, whereas expenditure on AHPs comprises less than 5%. The cost impact of every 10% increase in remote nurse and AHP annual turnover has been quantified as an extra A$6.12 per primary care consultation, which equates, on average, to an extra A$400000 per remote clinic, and an extra A$21million overall for the NT Department of Health each year. The average real expenditure per primary care consultation has decreased from A$273 in 2007 to A$197 in 2015, representing a statistically significant linear trend reduction of A$7.71 per consultation annually. What are the implications for practitioners (and other decision-makers)? Adjusting policy settings away from the high use of short-term staff to investment in appropriate training 'pipelines' for the remote primary care workforce may, in the medium and longer term, result in reduced turnover of resident staff and associated cost savings. Targeted recruitment and retention strategies that ensure individual primary care workers are an optimal fit with the remote communities in which they work, together with improved professional and personal support for staff residing in remote communities, may also help reduce turnover, improve workforce stability and lead to stronger therapeutic relationships and better health outcomes.

Objective: This article describes the rationale for, and development of, an evidence-based rural typology as the basis for an incentive scheme to improve medical workforce retention. This case study describes the key factors associated with ensuring that research evidence is translated into rural health policy and program implementation., Design: Case study., Setting: Rural and remote Australia., Results: The development and implementation of the Modified Monash Model in Australia demonstrates some of the key facilitators of knowledge exchange. These include: sound evidence based on good empirical data and rigorous methodology; transparency to peers and stakeholders; the importance of long-term commitment to rural health research; the credibility of the researcher; multiple modes of communication of results; real world validation and amplification of results; patience and persistence underscored by the commitment of researchers to achieving more equitable outcomes for rural and remote doctors; serendipity in terms of timing; and a governmental culture that values evidence-based outcomes., Conclusion: The knowledge exchange process is neither easy nor simple and rarely rapid. It often requires the engagement of communities, professional associations, health care providers, researchers, policy-makers and funders. Implementation of evidence into rural health policies and programs benefits all parties through significant improvements in efficiency, effectiveness and equity., (© 2018 National Rural Health Alliance Ltd.)

Background: Visiting services address the problem of workforce deficit and access to effective primary health care services in isolated remote and rural locations. Little is known about their impact or effectiveness and thereby the extent to which they are helping to reduce the disparity in access and health outcomes between people living in remote areas compared with people living in urban regions of Australia. The objective of this study was to answer the question "What is the impact or effectiveness when different types of primary health care services visit, rather than reside in, rural and remote communities?", Method: We conducted a systematic review of peer-reviewed literature from established databases. We also searched relevant websites for 'grey' literature and contacted several key informants to identify other relevant reference material. All papers were reviewed by at least two assessors according to agreed inclusion and exclusion criteria., Results: Initially, 345 papers were identified and, from this selection, 17 papers were considered relevant for inclusion. Following full paper review, another ten papers were excluded leaving seven papers that provided some information about the impact or effectiveness of visiting services. The papers varied with regard to study design (ranging from cluster randomised controlled trials to a case study), research quality, and the strength of their conclusions. In relation to effectiveness or impact, results were mixed. There was a lack of consistent data regarding the features or characteristics of visiting services that enhance their effectiveness or impact. Almost invariably the evaluations assessed the service provided but only two papers mentioned any aspect of the visiting features within which service provision occurred such as who did the visiting and how often they visited., Conclusions: There is currently an inadequate evidence base from which to make decisions about the effectiveness of visiting services or how visiting services should be structured in order to achieve better health outcomes for people living in remote and rural areas. Given this knowledge gap, we suggest that more rigorous evaluation of visiting services in meeting community health needs is required, and that evaluation should be guided by a number of salient principles.

Visiting health services are a feature of health care delivery in rural and remote contexts. These services are often described as 'fly-in fly-out' or 'drive-in drive-out'. Posing the question 'What are the different types of visiting models of primary health care being used in rural and remote communities?', the objective of this article was to describe a typology of models of health services that visit remote communities. A systematic review of peer-reviewed literature from established databases was undertaken. Data were extracted from 20 papers (16 peer-reviewed papers and four from other sources), which met the inclusion criteria. From the available evidence, it was difficult to develop a typology of services. The central feature of service providers visiting rural and remote districts on a regular basis was consistent, although the service provider's geographical base varied and the extent to which the same service provider should be providing the service was not consistently endorsed. While a clear typology did not emerge from the systematic review, it became apparent that a set of guiding principles might be more helpful to service providers and planners. Focusing policy and decision-making on important principles of visiting services, rather than their typological features, is likely to be of ultimately more benefit to the health outcomes of people who live in rural and remote communities., (© 2018 National Rural Health Alliance Ltd.)

Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro , autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK , with or without Drosophila Mo25 , did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux. Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium., (Copyright © 2018 by the American Society of Nephrology.)

Background: International evidence suggests that a key to improving health and attaining more equitable health outcomes for disadvantaged populations is a health system with a strong primary care sector. Longstanding problems with health workforce supply and turnover in remote Aboriginal communities in the Northern Territory (NT), Australia, jeopardise primary care delivery and the effort to overcome the substantial gaps in health outcomes for this population. This research describes temporal changes in workforce supply in government-operated clinics in remote NT communities through a period in which there has been a substantial increase in health funding., Methods: Descriptive and Markov-switching dynamic regression analysis of NT Government Department of Health payroll and financial data for the resident health workforce in 54 remote clinics, 2004-2015. The workforce included registered Remote Area Nurses and Midwives (nurses), Aboriginal Health Practitioners (AHPs) and staff in administrative and logistic roles., Main Outcome Measures: total number of unique employees per year; average annual headcounts; average full-time equivalent (FTE) positions; agency employed nurse FTE estimates; high and low supply state estimates., Results: Overall increases in workforce supply occurred between 2004 and 2015, especially for administrative and logistic positions. Supply of nurses and AHPs increased from an average 2.6 to 3.2 FTE per clinic, although supply of AHPs has declined since 2010. Each year almost twice as many individual NT government-employed nurses or AHPs are required for each FTE position. Following funding increases, some clinics doubled their nursing and AHP workforce and achieved relative stability in supply. However, most clinics increased staffing to a much smaller extent or not at all, typically experiencing a "fading" of supply following an initial increase associated with greater funding, and frequently cycling periods of higher and lower staffing levels., Conclusions: Overall increases in workforce supply in remote NT communities between 2004 and 2015 have been affected by continuing very high turnover of nurses and AHPs, and compounded by recent declines in AHP supply. Despite substantial increases in resourcing, an imperative remains to implement more robust health service models which better support the supply and retention of resident health staff.

Background: There are limited respite services for palliative care patients and their families in the Northern Territory (NT). The high prevalence of complex chronic diseases, limited access to primary care services, and the poor living situations of many Aboriginal and Torres Strait Islander Australians result in high hospitalisation rates and pressure on tertiary health services. Palliative Care NT identified a need for a flexible, community based, culturally appropriate respite service in Alice Springs. It was of particular interest to assess the impact of the respite service on the extent to which hospital resources were accessed by this population of patients., Methods: Respite service use and hospital use data were collected over two time periods: the 12 months prior to the establishment of the service; and the first 10 months of the operation of the service. The financial implications of the facility were assessed in terms of the National Weighted Activity Unit (NWAU). Of primary interest in this study was the impact of the respite service on admissions to the Emergency Department (ED), to the Wards, and to the Intensive Care Unit (ICU). The amount of ventilator hours consumed was also of interest., Results: Overall, there was a mean cost saving of $1882.50 per episode for hospital admissions with a reduction in: hospital admissions; mean length of stay; Intensive Care Unit (ICU) hours; and ventilator hours., Conclusions: The establishment of the respite service has met an important and unmet need in Alice Springs: provision of respite where none has existed before. The service did assist with savings to the health department which could contribute to the cost of the facility over time. Two features of the respite facility that may have contributed to the savings generated were the enhanced coordination of care for patients with complex chronic diseases, as well as improved medication compliance and symptom management.

The MEK1 kinase directly phosphorylates ERK2, after the activation loop of MEK1 is itself phosphorylated by Raf. Studies over the past decade have revealed a large number of disease-related mutations in the MEK1 gene that lead to tumorigenesis and abnormal development. Several of these mutations result in MEK1 constitutive activity, but how they affect MEK1 regulation and function remains largely unknown. Here, we address these questions focusing on two pathogenic variants of the Phe-53 residue, which maps to the well-characterized negative regulatory region of MEK1. We found that these variants are phosphorylated by Raf faster than the wild-type enzyme, and this phosphorylation further increases their enzymatic activity. However, the maximal activities of fully phosphorylated wild-type and mutant enzymes are indistinguishable. On the basis of available structural information, we propose that the activating substitutions destabilize the inactive conformation of MEK1, resulting in its constitutive activity and making it more prone to Raf-mediated phosphorylation. Experiments in zebrafish revealed that the effects of activating variants on embryonic development reflect the joint control of the negative regulatory region and activating phosphorylation. Our results underscore the complexity of the effects of activating mutations on signaling systems, even at the level of a single protein., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective Improving access to primary health care (PHC) remains a key issue for rural residents and health service planners. This study aims to show that how access to PHC services is measured has important implications for rural health service and workforce planning. Methods A more sophisticated tool to measure access to PHC services is proposed, which can help health service planners overcome the shortcomings of existing measures and long-standing access barriers to PHC. Critically, the proposed Index of Access captures key components of access and uses a floating catchment approach to better define service areas and population accessibility levels. Moreover, as demonstrated through a case study, the Index of Access enables modelling of the effects of workforce supply variations. Results Hypothetical increases in supply are modelled for a range of regional centres, medium and small rural towns, with resulting changes of access scores valuable to informing health service and workforce planning decisions. Conclusions The availability and application of a specific 'fit-for-purpose' access measure enables a more accurate empirical basis for service planning and allocation of health resources. This measure has great potential for improved identification of PHC access inequities and guiding redistribution of PHC services to correct such inequities. What is known about the topic? Resource allocation and health service planning decisions for rural and remote health settings are currently based on either simple measures of access (e.g. provider-to-population ratios) or proxy measures of access (e.g. standard geographical classifications). Both approaches have substantial limitations for informing rural health service planning and decision making. What does this paper add? The adoption of a new improved tool to measure access to PHC services, the Index of Access, is proposed to assist health service and workforce planning. Its usefulness for health service planning is demonstrated using a case study to hypothetically model changes in rural PHC workforce supply. What are the implications for practitioners? The Index of Access has significant potential for identifying how rural and remote primary health care access inequities can be addressed. This critically important information can assist health service planners, for example those working in primary health networks, to determine where and how much redistribution of PHC services is needed to correct existing inequities.

Background: The geographical maldistribution of the health workforce is a persisting global issue linked to inequitable access to health services and poorer health outcomes for rural and remote populations. In the Northern Territory (NT), anecdotal reports suggest that the primary care workforce in remote Aboriginal communities is characterised by high turnover, low stability and high use of temporary staffing; however, there is a lack of reliable information to guide workforce policy improvements. This study quantifies current turnover and retention in remote NT communities and investigates correlations between turnover and retention metrics and health service/community characteristics., Methods: This study used the NT Department of Health 2013-2015 payroll and financial datasets for resident health workforce in 53 remote primary care clinics. Main outcome measures include annual turnover rates, annual stability rates, 12-month survival probabilities and median survival., Results: At any time point, the clinics had a median of 2.0 nurses, 0.6 Aboriginal health practitioners (AHPs), 2.2 other employees and 0.4 additional agency-employed nurses. Mean annual turnover rates for nurses and AHPs combined were extremely high, irrespective of whether turnover was defined as no longer working in any remote clinic (66%) or no longer working at a specific remote clinic (128%). Stability rates were low, and only 20% of nurses and AHPs remain working at a specific remote clinic 12 months after commencing. Half left within 4 months. Nurse and AHP turnover correlated with other workforce measures. However, there was little correlation between most workforce metrics and health service characteristics., Conclusions: NT Government-funded remote clinics are small, experience very high staff turnover and make considerable use of agency nurses. These staffing patterns, also found in remote settings elsewhere in Australia and globally, not only incur higher direct costs for service provision-and therefore may compromise long-term sustainability-but also are almost certainly contributing to sub-optimal continuity of care, compromised health outcomes and poorer levels of staff safety. To address these deficiencies, it is imperative that investments in implementing, adequately resourcing and evaluating staffing models which stabilise the remote primary care workforce occur as a matter of priority.

Introduction: A Centre of Research Excellence (CRE) in Rural and Remote Primary Healthcare was established in 2012 with the goal of providing evidence to inform policy development to increase equity of access to quality health care and the identification of services that should be available to the diverse communities characterising Australia. This article reports on the key findings from seven CRE service evaluations to better understand what made these primary health care (PHC) models work where they worked, and why., Methods: We conducted a narrative synthesis of 15 articles reporting on seven CRE service evaluations of different PHC models published between 2012 and 2015., Results: Three different contexts for PHC reform were evaluated: community, regional and clinic based. Themes identified were factors that enabled changes to PHC delivery, processes that supported services to improve access to PHC and requirements for service adaptation to promote sustainability. In both Indigenous and mainstream community settings, the active engagement with local communities, and their participation in, or leadership of, shared decision-making was reported across the three themes. In addition, local governance processes, informed by service activity and impact data, enabled these service changes to be sustained over time. The considerations were different for the outreach, regional and clinic services that relied on internal processes to drive change because they did not require the cooperation of multiple organisations to succeed., Conclusions: The review highlighted that shared decision-making, negotiation and consultation with communities is important and should be used to promote feasible strategies that improve access to community-based PHC services. There is a growing need for service evaluations to report on the feasibility, acceptability and fit of successful service models within context, in addition to reach and effectiveness in order to provide evidence for local dissemination, adaption and implementation strategies.

Background: Improved Primary Health Care (PHC) utilisation is central to reducing the unacceptable morbidity and mortality rates characterising populations living in remote communities. Despite poorer health, significant inequity characterises the funding of PHC services in Australia's most remote areas. This pilot study sought to ascertain what funding is required to ensure equitable access to sustainable, high quality primary health care irrespective of geographical remoteness of communities., Methods: High performing remote Primary Health Care (PHC) services were selected using improvement measures from the Australian Primary Care Collaboratives Program and validated by health experts. Eleven PHC services provided data relating to the types of services provided, level of service utilisation, human resources, operating and capital expenses. A further four services that provide visiting PHC to remote communities provided information on the level and cost of these services. Demographic data for service catchment areas (including estimated resident population, age, Indigenous status, English spoken at home and workforce participation) were obtained from the Australian Bureau of Statistics 2011 census. Formal statistical inference (p-values) were derived in the linear regression via the nonparametric bootstrap., Results: A direct linear relationship was observed between the total cost of resident PHC services and population, while cost per capita decreased with increasing population. Services in smaller communities had a higher number of nursing staff per 1000 residents and provided more consultations per capita than those in larger communities. The number of days of visiting services received by a community each year also increased with population. A linear regression with bootstrapped statistical inference predicted a significant regression equation where the cost of resident services per annum is equal to $1,251,893.92 + ($1698.83 x population) and the cost of resident and visiting services is equal to $1,378,870.85 + ($2600.00 x population)., Conclusions: The research findings provide empirical evidence based on real costs to guide funding for remote PHC services that takes into account the safety and equity requirements for a minimum viable service. This method can be used as a transparent, coordinated approach to ensure the equitable delivery of sustainable, high quality PHC in remote communities. This will in turn contribute to improved health outcomes.

Background: Chronic kidney disease (CKD) is a worldwide public health issue. From 2009 to 2014, the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester (NIHR CLAHRC GM) in England ran 4 phased, 12-month quality improvement (QI) projects with 49 primary care practices in GM. Two measureable aims were set - halve undiagnosed CKD in participating practices using modelled estimates of prevalence; and optimise blood pressure (BP) control (<140/90 mm Hg in CKD patients without proteinuria; <130/80 mm Hg in CKD patients with proteinuria) for 75% of recorded cases of CKD. The 4 projects ran as follows: P1 = Project 1 with 19 practices (September 2009 to September 2010), P2 = Project 2 with 11 practices (March 2011 to March 2012), P3 = Project 3 with 12 practices (September 2012 to October 2013), and P4 = Project 4 with 7 practices (April 2013 to March 2014)., Methods: Multifaceted intervention approaches were tailored based on a contextual analysis of practice support needs. Data were collected from practices by facilitators at baseline and again at project close, with self-reported data regularly requested from practices throughout the projects., Results: Halving undiagnosed CKD as per aim was exceeded in 3 of the 4 projects. The optimising BP aim was met in 2 projects. Total CKD cases after the programme increased by 2,347 (27%) from baseline to 10,968 in a total adult population (aged ≥18 years) of 231,568. The percentage of patients who managed to appropriate BP targets increased from 34 to 74% (P1), from 60 to 83% (P2), from 68 to 71% (P3), and from 63 to 76% (P4). In nonproteinuric CKD patients, 88, 90, 89, and 91%, respectively, achieved a target BP of <140/90 mm Hg. In proteinuric CKD patients, 69, 46, 48, and 45%, respectively, achieved a tighter target of <130/80 mm Hg. Analysis of national data over similar timeframes indicated that practices participating in the programme achieved higher CKD detection rates., Conclusions: Participating practices identified large numbers of "missing" CKD patients with comparator data showing they outperformed non-QI practices locally and nationally over similar timeframes. Improved BP control also occurred through this intervention, but overall achievement of the tighter BP target in proteinuric patients was notably less.

Introduction: The study identifies the differences between rural health and remote health and describes key distinctive characteristics of remote health., Methods: The study used a mixed method approach of interviews and questionnaires (utilising a Likert scale) with expert stakeholders in rural health and remote health. A total of 45 interviews were conducted with experts selected from every state and territory of Australia. Of these, 41 also completed a questionnaire, of which 21 respondents were female, 20 identified predominantly as academics while six, five and five indicated that they worked in policy, advocacy and as a practitioner, respectively. Thirteen worked in rural health, 10 in remote health and 18 in both; 23 participants worked in Aboriginal and/or Torres Strait Islander health. Respondents had worked in rural health or remote health for mean periods of 13 years and 8 years, respectively., Results: Means for each of 15 characteristics indicated that respondents viewed each characteristic as different in remote health compared to rural health. Interviews confirmed these perceived differences, with particular emphasis on isolation, poor service access and the relatively high proportion of Indigenous residents. Those working in remote and Aboriginal health most strongly identified these distinctions., Conclusions: A detailed and rigorous description of the discipline of remote health, and the differences to rural health, will assist policymakers, health planners, teachers and researchers to develop an appropriate workforce, models of service delivery and policy that are relevant, appropriate and effective in order to ensure a more equitable distribution of resources and health outcomes across this vast continent.

Introduction: Many rural communities continue to experience an undersupply of primary care doctor services. While key professional factors relating to difficulties of recruitment and retention of rural primary care doctors are widely identified, less attention has been given to the role of community and place aspects on supply. Place-related attributes contribute to a community's overall amenity or attractiveness, which arguably influence both rural recruitment and retention relocation decisions of doctors. This bi-national study of Australia and the USA, two developed nations with similar geographic and rural access profiles, investigates the extent to which variations in community amenity indicators are associated with spatial variations in the supply of rural primary care doctors., Methods: Measures from two dimensions of community amenity: geographic location, specifically isolation/proximity; and economics and sociodemographics were included in this study, along with a proxy measure (jurisdiction) of a third dimension, environmental amenity. Data were chiefly collated from the American Community Survey and the Australian Census of Population and Housing, with additional calculated proximity measures. Rural primary care supply was measured using provider-to-population ratios in 1949 US rural counties and in 370 Australian rural local government areas. Additionally, the more sophisticated two-step floating catchment area method was used to measure Australian rural primary care supply in 1116 rural towns, with population sizes ranging from 500 to 50 000. Associations between supply and community amenity indicators were examined using Pearson's correlation coefficients and ordinary least squares multiple linear regression models., Results: It was found that increased population size, having a hospital in the county, increased house prices and affluence, and a more educated and older population were all significantly associated with increased workforce supply across rural areas of both countries. While remote areas were strongly linked with poorer supply in Australia, geographical remoteness was not significant after accounting for other indicators of amenity such as the positive association between workforce supply and coastal location. Workforce supply in the USA was negatively associated with fringe rural area locations adjacent to larger metropolitan areas and characterised by long work commutes. The US model captured 49% of the variation of workforce supply between rural counties, while the Australian models captured 35-39% of rural supply variation., Conclusions: These data support the idea that the rural medical workforce is maldistributed with a skew towards locating in more affluent and educated areas, and against locating in smaller, poorer and more isolated rural towns, which struggle to attract an adequate supply of primary care services. This evidence is important in understanding the role of place characteristics and rural population dynamics in the recruitment and retention of rural doctors. Future primary care workforce policies need to place a greater focus on rural communities that, for a variety of reasons, may be less attractive to doctors looking to begin or remain working there.

Objective: To synthesise key Australian empirical rural retention evidence and outline implications and potential applications for policymaking., Design: A comprehensive search of Medline, PsychINFO, CINAHL plus, Scopus and EMBASE revealed eight peer-reviewed empirical studies published since 2000 quantifying factors associated with actual retention., Setting and Participants: Rural and remote Australian primary health care workers., Main Outcome Measures: Hazard ratios (hazard of leaving rural), mean length of stay in current rural position and odds ratios (odds of leaving rural)., Results: A broad range of geographical, professional, financial, educational, regulatory and personal factors are strongly and significantly associated with the rural retention of Australian primary health care workers. Important factors included geographical remoteness and population size, profession, providing hospital services, practising procedural skills, taking annual leave, employment grade, employment and payment structures, restricted access to provider numbers, country of training, vocational training, practitioner age group and cognitive behavioural coaching. These findings suggest that retention strategies should be multifaceted and 'bundled', addressing the combination of modifiable factors most important for specific groups of Australian rural and remote primary health care workers, and compensating health professionals for hardships they face that are linked to less modifiable factors., Conclusions: The short retention of many Australian rural and remote Allied Health Professionals and GPs, particularly in small, outer regional and remote communities, requires ongoing policy support. The important retention patterns highlighted in this review provide policymakers with direction about where to best target retention initiatives, as well as an indication of what they can do to improve retention., (© 2016 National Rural Health Alliance Inc.)

Background: Remote Australia is a complex environment characterized by workforce shortages, isolated practice, a large resident Indigenous population, high levels of health need, and limited access to services. In recent years, there has been an increasing trend of utilizing a short-term visiting (fly-in/fly-out) health workforce in many remote areas. However, there is a dearth of evidence relating to the impact of this transitory workforce on the existing resident workforce, consumer satisfaction, and the effectiveness of current services., Objective: This study aims to provide rigorous empirical data by addressing the following objectives: (1) to identify the impact of short-term health staff on the workload, professional satisfaction, and retention of resident health teams in remote areas; (2) to identify the impact of short-term health staff on the quality, safety, and continuity of patient care; and (3) to identify the impact of short-term health staff on service cost and effectiveness., Methods: Mixed methods will be used. Administrative data will be extracted that relates to all 54 remote clinics managed by the Northern Territory Department of Health, covering a population of 35,800. The study period will be 2010 to 2014. All 18 Aboriginal Community-Controlled Health Services in the Northern Territory will also be invited to participate. We will use these quantitative data to describe staffing stability and turnover in these communities, and then utilize multiple regression analyses to determine associations between the key independent variables of interest (resident staff turnover, stability or median survival, and socioeconomic status, community size, and per capita funding) and dependent variables related to patient care, service cost, quality, and effectiveness. The qualitative component of the study will involve in-depth interviews and focus groups with staff and patients, respectively, in six remote communities. Three communities will be high staff turnover communities and three characterized by low turnover. This will provide information on service quality, impact on resident and visiting staff, and patient satisfaction with the services. The research team will work with staff, patients, and a key stakeholder group of senior policymakers to develop workforce strategies to maintain or attain remote health workforce stability., Results: The study commenced in 2015. As of October 2016, fieldwork has been almost completed and quantitative analysis has commenced. Results are expected to be published in 2017., Conclusions: The study has commenced, but it is too early to provide results or conclusions., Competing Interests: Conflicts of Interest: None declared.

Background: In the Northern Territory (NT) there is a lack of respite services available to palliative care patients and their families. Indigenous people in the NT suffer substantially higher rates of poorly controlled chronic disease and premature mortality associated with poor heath than the Australian population as a whole. The need for a flexible, community based, culturally appropriate respite service in Alice Springs was identified and, after the service had been operating for 10 months, a qualitative evaluation was conducted to investigate the experiences of people involved in the use and operation of the service., Methods: Semi-structured interviews were conducted with patients, carers, referrers, and stakeholders. A total of 20 people were interviewed. Interpretative Phenomenological Analysis was used inductively to analyse the transcripts. Two case studies are also described which illustrate in greater detail the impact the respite service has had on people's lives., Results: From the semi-structured interviews, two superordinate themes along with a number of sub themes were developed. The two superordinate themes described both "The Big Picture" considerations as well as the pragmatics of "Making the Service Work". The sub themes highlighted issues such as being stuck at home and the relief that respite provided. The case studies poignantly illustrate the difference the respite service made to the quality of life of two patients., Discussion: The findings clearly indicate an improvement in quality of life for respite patients and their carers. The respite service enabled improved care coordination of chronic and complex patients as well as improved medication compliance and symptom management. As a result of this evaluation a number of recommendations to continue and improve the service are provided.

Background: Chronic kidney disease (CKD) is common and a significant marker of morbidity and mortality. Its management in primary care is essential for maintenance of cardiovascular health, avoidance of acute kidney injury (AKI) and delay in progression to end-stage renal disease. Although many guidelines and interventions have been established, there is global evidence of an implementation gap, including variable identification rates and low patient communication and awareness. The objective of this study is to understand the factors enabling and constraining the implementation of CKD interventions in primary care., Methods: A rapid realist review was conducted that involved a primary literature search of three databases to identify existing CKD interventions in primary care between the years 2000 and 2014. A secondary search was performed as an iterative process and included bibliographic and grey literature searches of reference lists, authors and research groups. A systematic approach to data extraction using Normalisation Process Theory (NPT) illuminated key mechanisms and contextual factors that affected implementation., Results: Our primary search returned 710 articles that were narrowed down to 18 relevant CKD interventions in primary care. Our findings suggested that effective management of resources (encompassing many types) was a significant contextual factor enabling or constraining the functioning of mechanisms. Three key intervention features were identified from the many that contributed to successful implementation. Firstly, it was important to frame CKD interventions appropriately, such as within the context of cardiovascular health and diabetes. This enabled buy-in and facilitated an understanding of the significance of CKD and the need for intervention. Secondly, interventions that were compatible with existing practices or patients' everyday lives were readily accepted. In contrast, new systems that could not be integrated were abandoned as they were viewed as inconvenient, generating more work. Thirdly, ownership of the feedback process allowed users to make individualised improvements to the intervention to suit their needs., Conclusions: Our rapid realist review identified mechanisms that need to be considered in order to optimise the implementation of interventions to improve the management of CKD in primary care. Further research into the factors that enable prolonged sustainability and cost-effectiveness is required for efficient resource utilisation.