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Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine1,2. Here we reduced this complexity by focusing on cellular organization—a key readout and driver of cell behaviour3,4—at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the ‘wiring’ of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring.

Objective The association between neighborhood environments and health outcomes has long been recognized, but the importance of environmental factors is less well examined in osteoarthritis (OA). We aimed to give an overview of the literature examining the role of neighborhood built environments in the context of OA self-management. Material and Methods A literature search between 2000 and 2019 was performed using a scoping methodology. Literature examining the influence of neighborhood built environments on health and other outcomes in people with OA, mixed or unspecified arthritis were screened by two independent reviewers. Seven domains were pre-determined based on the World Health Organization European Healthy Cities Framework. Sub-domains and themes were synthesized from the literature. Results We included 27 studies across seven pre-determined domains, 23 sub-domains. We identified 6 key outcomes of physical activity, quality of life, community participation, resource use, psychological health, and other physical health. The majority of studies emphasized the importance of neighborhood built environment on supporting OA self-management, particularly for facilitating physical activity. The impacts on other outcomes were also considered important but were less well studied, especially access to healthy food. Conclusions This review highlights the potential of better using the built environment to support OA management to address many different outcomes. Understanding the impacts of different environments is the first step, and designing new and novel ways to utilize neighborhoods is needed. Implementing strategies and public policies at a neighborhood level may be a more viable way to curb further increases in the OA epidemic than addressing individual factors alone.

Background Imaging data contains a substantial amount of information which can be difficult to evaluate by eye. With the expansion of high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis of the resulting images is essential to effectively extract biological information from this data. CellProfiler is a free, open source image analysis program which enables researchers to generate modular pipelines with which to process microscopy images into interpretable measurements. Results Herein we describe CellProfiler 4, a new version of this software with expanded functionality. Based on user feedback, we have made several user interface refinements to improve the usability of the software. We introduced new modules to expand the capabilities of the software. We also evaluated performance and made targeted optimizations to reduce the time and cost associated with running common large-scale analysis pipelines. Conclusions CellProfiler 4 provides significantly improved performance in complex workflows compared to previous versions. This release will ensure that researchers will have continued access to CellProfiler’s powerful computational tools in the coming years.

Leaching of nitrate through soil profiles is a major cause of soil acidification. Legume species differ in their ability to take up nitrate (NO

Our goal is to identify and understand cellular behaviors using 3D live imaging of cell organization. To do this, we image human inducible pluripotent stem cell (hiPSC) lines expressing fluorescently tagged protein representing specific cellular organelles and structures. To produce large numbers of standardized cell images, we developed an automated hiPSC culture procedure, to maintain, passage and Matrigel coat 6-well plastic plates and 96-well glass plates compatible with high-resolution 3D microscopy. Here we describe this system including optimization procedures and specific values for plate movement, angle of tips, speed of aspiration and dispense, seeding strategies and timing of every step. We validated this approach through a side-by-side comparison of quality control results obtained from manual and automated methods. Additionally, we developed an automated image-based colony segmentation and feature extraction pipeline to predict cell count and select wells with consistent morphology for high resolution 3D microscopy.

ObjectiveImplementation strategies, such as new models of service delivery, are needed to address evidence practice gaps. This paper describes the process of developing and operationalising a new model of service delivery to implement recommended care for people with knee osteoarthritis (OA) in a primary care setting.MethodsThree development stages occurred concurrently and iteratively. Each stage considered the healthcare context and was informed by stakeholder input. Stage 1 involved the design of a new model of service delivery (PARTNER). Stage 2 developed a behavioural change intervention targeting general practitioners (GPs) using the behavioural change wheel framework. In stage 3, the ‘Care Support Team’ component of the service delivery model was operationalised.ResultsThe focus of PARTNER is to provide patients with education, exercise and/or weight loss advice, and facilitate effective self-management through behavioural change support. Stage 1 model design: based on clinical practice guidelines, known evidence practice gaps in current care, chronic disease management frameworks, input from stakeholders and the opportunities and constraints afforded by the Australian primary care context, we developed the PARTNER service-delivery model. The key components are: (1) an effective GP consultation and (2) follow-up and ongoing care provided remotely (telephone/email/online resources) by a ‘Care Support Team’. Stage 2 GP behavioural change intervention: a multimodal behavioural change intervention was developed comprising a self-audit/feedback activity, online professional development and desktop software to provide decision support, patient information resources and a referral mechanism to the ‘Care Support Team’. Stage 3 operationalising the ‘care support team’—staff recruited and trained in evidence-based knee OA management and behavioural change methodology.ConclusionThe PARTNER model is the result of a comprehensive implementation strategy development process using evidence, behavioural change theory and intervention development guidelines. Technologies for scalable delivery were harnessed and new primary evidence was generated as part of the process.Trial registration number ACTRN12617001595303 (UTN U1111-1197-4809)

ObjectivesMusculoskeletal pain is a leading cause of disability globally. In geographically and socioeconomically diverse countries, such as Australia, care seeking when someone experiences musculoskeletal pain is varied and potentially influenced by their individual characteristics, access to practitioners or perceived trustworthiness of information. This study explored how consumers currently access healthcare, how well it is trusted and if sociodemographic factors influenced healthcare utilisation.DesignAnonymous online observational survey.SettingAustralia.ParticipantsA convenience sample of 831 community-based individuals (18+ years).Outcome measuresDescriptive analyses and generalised estimating equations were used to quantify healthcare-seeking behaviours, sources and trust of health information for (A) first-contact practitioners, (B) medical practitioners, and (C) other sources of information.ResultsOf the 761 respondents, 73% were females, 54% resided in capital cities. 68% of respondents had experienced pain or injury in more than one lower limb joint. Despite this, more than 30% of respondents only sought help when there had not been natural resolution of their pain. Physiotherapists had the highest odds of being seen, asked and trusted for healthcare information. The odds of seeking care from general practitioners were no higher than seeking information from an expert website. Older individuals and women exhibited higher odds of seeking, asking and trusting health information.ConclusionIntelligible and trustworthy information must be available for consumers experiencing lower limb pain. Individuals, particularly younger people, are seeking information from multiple, unregulated sources. This suggests that healthcare professionals may need to invest time and resources into improving the trustworthiness and availability of healthcare information to improve healthcare quality.

Osteoarthritis (OA) is a complex musculoskeletal disease and a leading cause of pain and disability worldwide. Hip and knee OA alone are major contributors to global disability, having notable effects on individual well-being, increasing the reliance of individuals on health-care services and contributing to a rise in the socioeconomic burden. Consistent, coordinated and tailored approaches are important for providing appropriate care to all people with OA, but despite the scale of the challenge many individuals are still not offered the safe, best-evidence treatments recommended for OA care. This Review discusses the core priority treatments for OA, including exercise and physical activity, weight-loss, education and support for self-management. Additional physical or psychological evidence-based adjunctive therapies and combined therapies that can be used to tailor individual programmes are also discussed. These options include cognitive behavioural therapy, heat therapy, walking aids and splints, manual therapies and transcutaneous electrical nerve stimulation. International examples of OA treatment options, models of care and resources available are also given. Many challenges still need to be addressed to advance the uptake of these conditions, including further discussion around the risks and costs involved with all treatments. Various core and adjunctive therapies are available for osteoarthritis (OA) that can have beneficial effects on the well-being of the individual; however, challenges remain in implementing best-evidence, high-value care.

Purpose: There is growing international interest in the implementation of structured osteoarthritis management programs (OAMPs) to deliver best evidence osteoarthritis (OA) care. A consortium of researchers, clinicians and consumers concerned with optimising implementation of OAMPs have established the ‘Joint Effort’ Initiative (the Initiative), endorsed by the Osteoarthritis Research Society International (OARSI) in 2018. A priority action of the Initiative is to evaluate the outcomes and implementation of existing OAMPs.Marked differences between existing international OAMP models include treatments offered, settings and mode of delivery, intensity, duration and health disciplines involved. There is some evidence of effectiveness from randomised controlled trials (RCTs) and longitudinal cohort studies reporting outcomes from OAMPS in different real-world settings, however, this research is still in its infancy. The effects of different OAMP models have not been compared head-to-head and given the prohibitive costs and logistics associated with comparing OAMP models in RCTs, it is unlikely that these trials will take place. Instead, we will leverage research efforts and costs that have already been spent by combining data from existing cohort studies to compare the outcomes of different OAMP models.We aim to combine Individual Patient Data (IPD) from the existing international OAMP cohorts and use meta-analytic techniques to address the following objectives: 1) Compare the short-, medium- and long-term changes in pain, physical function, body weight, Quality of Life, fear of movement and goal achievement between different OAMPs. 2) Determine the short-, medium- and long-term overall effects of OAMPs on pain and physical function for people with knee and hip OA. 3) Examine the characteristics of OAMP participants who achieved/ did not achieve the Patient Acceptable Symptom State (PASS), OMERACT-OARSI responder criteria, and completers vs dropouts. 4) Describe the implementation evaluation outcomes of OAMPsMethods: We will use de-identified IPD from nine existing OAMP clinical cohorts from Australia, Norway, Sweden, Netherlands, UK, New Zealand and USA. Clinical cohorts will be eligible if they are derived from a hip/knee OAMP in a real-world setting with the following components: i) personalised OA care; ii) package of care with reassessment and progression; iii) minimum of two core treatments of education, exercise, and/or weight-loss, and; iv) optional adjunctive treatments. We will include both published and unpublished data.Based on scoping work on the outcomes measures and time points currently collected by each OAMP, our primary outcomes will be the difference in pain (numerical rating scale 0-10) and function (Western Ontario and McMasters Osteoarthritis Index function score (WOMAC)), at 12-weeks. Secondary outcomes will be changes in pain and function at 26- and 52-weeks. Other secondary outcomes at 12-, 26- and 52- weeks will be changes in: body weight; quality of life (EuroQol, Short Form 12); disease specific measures (Knee Injury and Osteoarthritis Outcome score, Hip Disability and Osteoarthritis Outcome score, WOMAC); functional performance (30-second chair stand test, six-minute walk test); fear of movement; and patient satisfaction. We will report against the PASS, OMERACT-OARSI definition of responders/non-responders and examine implementation outcomes where available including the Osteoarthritis Quality Indicator Questionnaire, uptake, reach and fidelity.The IPD will be harmonised and aggregated to create one large dataset. We will use descriptive statistics to compare the characteristics of participants across OAMPs. We will take a two-step approach to IPD meta-analytic techniques. First, we will estimate the change in outcomes for each OAMP (pain, function and other outcomes) with multivariable regression modelling. Second, we will weight and pool estimates using random-effects methods to determine the overall effects on pain and function, account for differences in effects across studies and examine prognostic effects and interactions of characteristics (e.g. baseline symptomatic severity, functional performance) of participants who achieved/did not achieve the PASS, OMERACT OARSI responder criteria and those who completed/dropped out of the OAMPs.Results: This study has received ethical approval from the NSLHD Human Research Ethics Committee (Australia). Ethical approval for use of other cohort data is being sought by researchers in their respective countries. We have performed extensive work with the stakeholders involved to identify appropriate co-collected outcomes and will collaborate with the OA Trial Bank to store and collate the cohort data, the first database of its kind.Conclusions: This project will be the first to compare patient and implementation outcomes across international OAMPs. It will address a priority of the Initiative and make recommendations on the “optimal” OAMP model/s to use.

IntroductionThis protocol outlines the rationale, design and methods for the process and feasibility evaluations of the primary care management on knee pain and function in patients with knee osteoarthritis (PARTNER) study. PARTNER is a randomised controlled trial to evaluate a new model of service delivery (the PARTNER model) against ‘usual care’. PARTNER is designed to encourage greater uptake of key evidence-based non-surgical treatments for knee osteoarthritis (OA) in primary care. The intervention supports general practitioners (GPs) to gain an understanding of the best management options available through online professional development. Their patients receive telephone advice and support for OA management by a centralised, multidisciplinary ‘Care Support Team’. We will conduct concurrent process and feasibility evaluations to understand the implementation of this new complex health intervention, identify issues for consideration when interpreting the effectiveness outcomes and develop recommendations for future implementation, cost effectiveness and scalability.Methods and analysisThe UK Medical Research Council Framework for undertaking a process evaluation of complex interventions and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks inform the design of these evaluations. We use a mixed-methods approach including analysis of survey data, administrative records, consultation records and semistructured interviews with GPs and their enrolled patients. The analysis will examine fidelity and dose of the intervention, observations of trial setup and implementation and the quality of the care provided. We will also examine details of ‘usual care’. The semistructured interviews will be analysed using thematic and content analysis to draw out themes around implementation and acceptability of the model.Ethics and disseminationThe primary and substudy protocols have been approved by the Human Research Ethics Committee of The University of Sydney (2016/959 and 2019/503). Our findings will be disseminated to national and international partners and stakeholders, who will also assist with wider dissemination of our results across all levels of healthcare. Specific findings will be disseminated via peer-reviewed journals and conferences, and via training for healthcare professionals delivering OA management programmes. This evaluation is crucial to explaining the PARTNER study results, and will be used to determine the feasibility of rolling-out the intervention in an Australian healthcare context.Trial registration numberACTRN12617001595303; Pre-results.

Field experimental data of five experiments covering a wide range of growing conditions are assembled for wheat growth and cropping systems modeling. The data include an experiment on interactive effects of elevated CO2 by water and elevated CO2 by nitrogen fertilizer application from a Free-Air Carbon Dioxide Enrichment experiment (FACE) at Arizona in USA; a nitrogen rate fertilizer experiment from three locations and two years in The Netherlands; water deficit experiments at Lincoln in New Zealand and at Cunderdin in Australia; and a temperature sensitivity experiment at Obregon in Mexico. The data consist of 65 experimental treatments with more than 1000 detailed observations, with time series of development and growth, soil water and soil nitrogen dynamics, yield and yield components, daily weather, soil characteristics, and cultivar descriptions. These data have been used in various previous agronomic and crop modeling studies. Assembled data are quality checked and supplied in Agricultural Model Inter-comparison and Improvement (AgMIP) format. Data access via DOI 10.7910/DVN/V4P6PU.

Question Do people with musculoskeletal conditions better adhere to their home exercise programs when these are provided to them on an app with remote support compared to paper handouts? Design Randomised, parallel-group trial with intention-to-treat analysis. Participants Eighty participants with upper or lower limb musculoskeletal conditions were recruited to the trial. Each participant was prescribed a 4-week home exercise program by a physiotherapist at a tertiary teaching hospital in Australia. Participants were randomly assigned via a computer-generated concealed block randomisation procedure to either intervention (n=40) or control (n=40) groups. Intervention Participants in the intervention group received their home exercise programs on an app linked to the freely available website www.physiotherapyexercises.com. They also received supplementary phone calls and motivational text messages. Participants in the control group received their home exercise programs as a paper handout. Outcome measures Blinded assessors collected outcome measures at baseline and 4 weeks. The primary outcome was self-reported exercise adherence. There were five secondary outcomes, which captured functional performance, disability, patient satisfaction, perceptions of treatment effectiveness, and different aspects of adherence. Results Outcomes were available on 77 participants. The mean between-group difference for self-reported exercise adherence at 4 weeks was 1.3/11 points (95% CI 0.2 to 2.3), favouring the intervention group. The mean between-group difference for function was 0.9/11 points (95% CI 0.1 to 1.7) on the Patient-Specific Functional Scale, also favouring the intervention group. There were no significant between-group differences for the remaining outcomes. Conclusion People with musculoskeletal conditions adhere better to their home exercise programs when the programs are provided on an app with remote support compared to paper handouts; however, the clinical importance of this added adherence is unclear. Trial registration ACTRN12616000066482. [Lambert TE, Harvey LA, Avdalis C, Chen LW, Jeyalingam S, Pratt CA, Tatum HJ, Bowden JL, Lucas BR (2017) An app with remote support achieves better adherence to home exercise programs than paper handouts in people with musculoskeletal conditions: a randomised trial. Journal of Physiotherapy 63: 161–167]

Background The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. Hypothesis/Objectives To report the components of biological and analytical variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in healthy dogs. Animals Fourteen healthy harrier hound dogs. Methods The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (CD), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated. Results The IoI was equal to 1.1 and the CD was 3.3 μg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 μg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 μg/dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. Conclusions and Clinical Importance False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large CD emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC.

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A systematic review of randomised controlled trials. To determine the effectiveness of 22 commonly administered physiotherapy interventions for people with spinal cord injuries (SCIs). The inclusion criteria contained 22 pairs of key interventions and outcomes. Each intervention and outcome was considered independently such that 22 brief reviews were conducted and summarised in this one paper. The interventions included hand, wheelchair, seated mobility, fitness, strength and gait training, as well as electrical stimulation, passive movements, stretch, cycling, exercise and transcutaneous electrical nerve stimulation (TENS). Interventions were compared with no or sham treatment, usual care or another physiotherapy intervention. The primary outcome for each review was one of the following: seated mobility, wheelchair mobility, hand function, gait, voluntary strength, joint mobility, fitness and pain. Data were extracted to determine mean between-group differences or risk ratios (95% confidence interval). Where possible, results were pooled in meta-analyses and the strength of evidence rated using Grading of Recommendations Assessment, Development and Evaluation. Thirty-eight randomised controlled trials met the inclusion criteria and were relevant to 15 of the brief reviews. The following four interventions were clearly effective: fitness, hand and wheelchair training as well as TENS; however, the strength of evidence was not high for any of these interventions. None of the other interventions were clearly effective. There is initial evidence to support four physiotherapy interventions, but there is still a long way to go to put a strong evidence base to the range of physiotherapy interventions commonly used to manage people with SCI.

To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care.We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged ≥45 years and have experienced knee pain ≥4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care.This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA.Australian New Zealand Clinical Trials Registry: ACTRN12617001595303 , date of registration 1/12/2017.

Background To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. Methods We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged ≥45 years and have experienced knee pain ≥4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients’ GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. Discussion This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12617001595303, date of registration 1/12/2017.

The objective of this study was to determine the inter-rater reliability and validity of using a telephone-based version of the spinal cord injury–secondary conditions scale (SCI–SCS). A psychometric study was conducted. The study was conducted in Royal North Shore Hospital, Sydney, Australia. Forty people with a complete or an incomplete spinal cord injury. Inter-rater reliability was tested by comparing the telephone-based version of the SCI–SCS administered on two different days by two different telephone assessors. Validity was tested by comparing the telephone-based version of the SCI–SCS with the paper-based version of the SCI–SCS. The median (interquartile range) age and time since injury were 54 (48–63) years and 28 (14–35) years, respectively. The intraclass correlation coefficient (95% confidence interval) reflecting the agreement between the telephone-based version of the SCI–SCS administered on two different days by two different assessors was 0.96 (0.93–0.98). The corresponding value reflecting agreement between the telephone-based assessment and the paper-based assessment was 0.90 (0.83–0.95). The telephone-based version of the SCI–SCS is a simple and a quick questionnaire to administer that has both inter-rater reliability and validity. It may be useful as a way to screen for secondary health conditions in low- and middle-income countries where it is not always feasible to provide routine face-to-face follow-ups and where literacy may be a problem.

Mixed retrospective-prospective cohort study. To determine 2-year survival following discharge from hospital after spinal cord injury in Bangladesh. Bangladesh. Medical records were used to identify all patients admitted in 2011 with a recent spinal cord injury to the Centre for Rehabilitation of the Paralysed, a large Bangladeshi hospital that specialises in care of people with spinal cord injury. Patients or their families were subsequently visited or contacted by telephone in 2014. Vital status and, where relevant, date and cause of death were determined by verbal autopsy. 350 of 371 people admitted with a recent spinal cord injury in 2011 were discharged alive from hospital. All but eleven were accounted for two years after discharge (97% follow-up). Two-year survival was 87% (95% CI 83% to 90%). Two-year survival of those who were wheelchair-dependent was 81% (95% CI 76% to 86%). The most common cause of death was sepsis due to pressure ulcers. In Bangladesh, approximately one in five people with spinal cord injury who are wheelchair-dependent die within two years of discharge from hospital. Most deaths are due to sepsis from potentially preventable pressure ulcers.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases. Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

Objectives: To explore the feasibility of conducting a full trial designed to determine the effectiveness of a model of community-based care for people with spinal cord injury in Bangladesh. Study Design: A pilot randomised trial. Setting: Community, Bangladesh. Subjects: Participants were 30 people with recent spinal cord injury who were wheelchair-dependent and soon to be discharged from hospital. Intervention: Participants randomised to the intervention group received a package of care involving regular telephone contact and three home visits over two years. Participants randomised to the control group received usual care consisting of a telephone call and an optional home visit. Main measures: Participants were assessed at baseline and two years after randomization. The primary outcome was mortality and secondary outcomes were measures of complications, depression, participation and quality of life. Results: A total of 24 participants had a complete spinal cord injury and six participants had an incomplete spinal cord injury. Median (interquartile) age and time since injury at baseline were 31 years (24 to 36) and 7 months (4 to 13), respectively. Two participants, one in each group, died. Five participants had pressure ulcers at two years. There were no notable impediments to the conduct of the trial and no significant protocol violations. The phone calls and home visits were delivered according to the protocol 87% and 100% of the time, respectively. Follow-up data were 99% complete. Conclusion: This pilot trial demonstrates the feasibility of a full clinical trial of 410 participants, which has recently commenced. Sponsorship: University of Sydney, Australia.

Within-participant randomised controlled trial. To determine whether strength training combined with usual care increases strength in partially paralysed muscles of people with recent spinal cord injury (SCI) more than usual care alone. SCI units in Australia and India. Thirty people with recent SCI undergoing inpatient rehabilitation participated in this 12-week trial. One of the following muscle groups was selected as the target muscle group for each participant: the elbow flexors, elbow extensors, knee flexors or knee extensors. The target muscle on one side of the body was randomly allocated to the experimental group and the same muscle on the other side of the body was allocated to the control group. Strength training was administered to the experimental muscle but not to the control muscle. Participants were assessed at baseline and 12 weeks later. The primary outcome was maximal isometric muscle strength, and the secondary outcomes were spasticity, fatigue and participants’ perception of function and strength. There were no dropouts, and participants received 98% of the training sessions. The mean (95% confidence interval (CI)) between-group difference for isometric strength was 4.3 Nm (1.9–6.8) with a clinically meaningful treatment effect of 2.7 Nm. The mean (95% CI) between-group difference for spasticity was 0.03/5 points (−0.25 to 0.32). Strength training increases strength in partially paralysed muscles of people with recent SCI, although it is not clear whether the size of the treatment effect is clinically meaningful. Strength training has no deleterious effects on spasticity.

Objective Percutaneous electrical stimulation of the motor point permits selective activation of a muscle. However, the definition and number of motor points reported for a given muscle varies. Our goal was to address these problems. Methods The area, location and number of motor points in human tibialis anterior were examined, using isometric dorsiflexion torque responses to electrical stimuli. Three methods were used: lowest electrical threshold, maximum muscle response, and approximate motor point. Results A single motor point was identified in 39/40 subjects regardless of method. The area of the site of lowest electrical threshold was smaller (median, 35mm 2 ) than those using the maximum muscle response (144mm 2 ) and approximate motor point (132mm 2 ). There was substantial, but not significant, between-subject variation in motor point location. Fifty three percent of motor points would have been missed if located only by reference to anatomical landmarks. Conclusions These results suggested that the motor point's location cannot be determined a priori and that the identification method will affect both area and location. Significance If it is important to maximally activate a single muscle in isolation, the motor point is best represented by the site producing a maximal but isolated muscle response at the lowest stimulation intensity.

For patients with osteoarthritis, the current palliative approach of analgesic prescription followed by joint replacement is often inappropriate. Instead, care should be tailored to the needs of individuals and targeted towards the central complaints of pain and functional limitation. So why are we still getting it wrong?

A diagnostic accuracy study.The objective was to determine the ability of people with SCI to accurately self-report S4-5 sensory and motor function.Outpatient clinic, Sydney, Australia.A consecutive series of thirty-four people who had sustained a SCI more than 1 year before the study, and who were attending an outpatient medical clinic were recruited. They were assessed on two occasions. On the first occasion, ability to self-report S4-5 sensory and motor function was assessed with four questions. On the second occasion, a rehabilitation physician performed a physical examination to determine participants' S4-5 sensory and motor function. The rehabilitation physician was unaware of the results of participants' self-report. Participants' self-reports were compared with results from the physical examination using likelihood ratios.The likelihood ratios (95% CI) associated with a positive response to the sensory and motor questions were 1.92 (1.0-3.6) and 2.4 (1.2-4.9), respectively. The likelihood ratios associated with a negative response to the sensory and motor questions were 0.1 (0.0-0.6) and 0.4 (0.1-1.2), respectively.People with SCI are reasonably accurate at self-reporting S4-5 sensory and motor function, although there is a high rate of false positives for S4-5 motor in those with motor levels below T10. In some situations it may be appropriate to use self-report rather than a physical examination to determine S4-5 sensory and motor function.

Question Do people with recently acquired paraplegia benefit from a six-week motor retraining program aimed at improving their ability to sit unsupported? Design A randomised controlled trial with concealed allocation, assessor blinding, and intention-totreat analysis. Participants 32 people with recently acquired paraplegia and limited ability to sit unsupported. Intervention All participants undertook standard inpatient rehabilitation over a six-week period. Experimental participants received three additional 30-minute sessions per week of motor retraining directed at improving their ability to sit unsupported. Outcome measures The three primary outcomes were the Maximal Lean Test, Maximal Sideward Reach Test, and the Performance Item of the Canadian Occupational Performance Measure (COPM). The secondary outcomes were the Satisfaction Item of the COPM, Participants' Impressions of Change, Clinicians' Impressions of Change, the T-shirt Test, and the Spinal Cord Injury Falls Concern Scale. Results The mean between-group differences for the Maximal Lean Test, Maximal Sideward Reach Test and the Performance Item of the COPM were –20 mm (95% CI –64 to 24), 5% arm length (95% CI –3 to 13) and 0.5 points (95% CI –0.5 to 1.5), respectively. The secondary outcomes did not differ significantly between groups. Conclusion People with recently acquired paraplegia do not benefit from a six-week motor retraining program directed specifically at improving their ability to sit unsupported. Their ability to sit unsupported does, however, improve over time, suggesting that the practice of activities of daily living has important carry-over effects on unsupported sitting, rendering additional training redundant. Trial registration ACTRN12608000464369.

Plant residues placed in soil in mesh bags do not mimic realistic decomposition conditions. Alternative techniques, e.g. combined particle size and density methods, have been proposed to monitor in situ decomposition of plant residues, but are not appropriately evaluated for their ability to quantitatively recover and characterise decomposing residues of a range of sizes mixed with soil over long incubation times. For this study, we used canola residues of three different starting sizes ( 106-μm by wet sieving, and then by repeated floatation and decantation, using water as a density agent, to recover and characterise decomposing canola residues from a mixture of >106-μm mineral plus organic materials into >106-to-500 and >500-μm fractions. On day 0, across the three residue-size treatments, the >500-μm fraction recovered 93–96% of canola residue-C, with water-soluble residue-C loss during the recovery process quantified as representing further 4–5%. The rate of loss of residue-C in the >500-μm fraction was the largest, matching well the cumulative respiration loss of residue-C. The recovery of canola residue-C in the >500-μm fraction, determined as percent of cumulative CO2–C respired of added C, decreased to 72–76% by the end of incubation, likely due to progressive generation of finer-sized residues and microbial/faunal metabolites. The increase of N in the >500-μm fraction accounted for ca. 40% of total soil N immobilised in the residue-amended soil. The extent and patterns of changes in C, N and S contents, and C-to-N and C-to-S ratios of separated fractions were similar among all the residue treatments during decomposition, except for the ground-residue treatment. The combined size and density separation procedure can be used to study decomposition in situ of soil-mixed plant residues of different sizes that are usually found in agro-ecosystems.

Mixed retrospective-prospective cohort study. To determine psychological and socioeconomic status, complications and quality of life in people with spinal cord injuries (SCI) after discharge from a hospital in Bangladesh. Bangladesh. All patients admitted in 2011 with a recent SCI to a hospital in Bangladesh were identified. Patients were interviewed by telephone in 2014 using translated versions of the SF12, the SCI Secondary Conditions Scale, the Centre for Epidemiologic Studies Depression Scale (CESDS) and the Participation Component of the WHODAS. Questions were also asked about employment, living and financial situation, and opportunities to get out of bed and out of the house. Data were stratified by ability to walk on discharge. A total of 350 people were discharged with a recent SCI in 2011. By 2014, 55 had died. Of those still living, 283 were interviewed (96% follow-up rate). At the time of interview, 47% of participants were employed. One-quarter (26%) of those who were wheelchair-dependent had a pressure ulcer. The mean (s.d.) scores for the Mental and Physical Component of the SF12 were 32.0 points (5.5) and 35.8 points (3.9), respectively. The median (interquartile range) scores for the SCI Secondary Conditions Scale, CESDS and WHODAS for those who were wheelchair-dependent were 15% (10 to 19), 11 points (9 to 18) and 26 points (23 to 26), respectively. Many people with SCI in Bangladesh are house-bound, unemployed, living in poverty and have pressure ulcers. They experience moderate rates of depression and report limited quality of life.

No information is available on the role of particle size of canola (Brassica napus) residue in altering C mineralization and nutrient (N, S) cycling in soil. We studied decomposition of canola residue (at 20±1 °C temperature and 10% moisture (w/w) for 6 months to elucidate the effect of its particle size ( Averaged over time, particle size of canola residue did not significantly affect C mineralization rate, the size of microbial-C and microbial-N pools, or the extent of CaCl2-extractable S immobilization, but altered the extent of mineral-N ( NH 4 + , NO 3 − ) immobilization and water-soluble organic C (W-SOC) depletion. A rapid decrease in C mineralization rate in the first week matched the rapid depletion of W-SOC, especially for the

The cropping systems simulation model APSIM-Nwheat was tested against detailed field measurements representing possible growing conditions under future climate change scenarios. Increasing average temperatures by 1.7 °C observed over several seasons at Obregon, Mexico reduced the time to flowering by 11 days and resulted in a decline of total biomass and grain yield. These effects were reproduced by the model, except when the observed total biomass inexplicably rose again in the fourth and fifth year, despite higher temperature and a much shorter growing time. In a water stress experiment, the effects of different timing and duration of water deficit on crop growth and yield were reproduced with the model for a rain-shelter experiment at Lincoln, New Zealand where observed grain yields were reduced from 10 to 4 t ha −1 due to increased water deficit. In experiments from Western Australia, reduced growth and yields due to extreme terminal water deficit were also reproduced with the model where measured yields fall below 0.5 t ha −1 . In the Maricopa Free Air Carbon-Dioxide Enrichment (FACE) experiment in Arizona, USA, the largest yield increase occurred with elevated CO 2 in the dry and high N treatments, whereas little or no response was observed in the wet and low N supply treatments, as simulated with the model. Combining elevated CO 2 with increased temperature in a sensitivity analysis, two levels of water supply and a range of N applications indicated a positive effect of elevated CO 2 on yield as long as N was not limiting growth. Increased temperature and reduced water supply reduced yields and the yield response to N supply under ambient and elevated CO 2 . Grain protein concentrations were reduced under elevated CO 2 , but the difference was minor with ample N fertiliser. Evapotranspiration was reduced under elevated CO 2 . Higher temperatures increased evapotranspiration with low N input, but reduced it with ample N fertiliser, resulting in a reduction and an increase, respectively, in drainage below the root zone. In the Mediterranean environment of Western Australia the impact of elevated CO 2 and increased temperature on grain yield was in average positive, but varied with seasonal rainfall distribution. Based on the range of model testing experiments and the sensitivity analysis, APSIM-Nwheat was found suitable for studies on directional impacts of future climate change on wheat production. Due to some large discrepancies between simulated and observed data, field experiments representing only a limited range of possible climate change scenarios and the large possible range of factorial interactions not tested, simulated quantitative effects with the model should be interpreted cautiously.

The overall quality and delivery of patient care is becoming increasingly important, especially in those diagnosed with cancer. Multidisciplinary clinics are a valuable adjunct to this, but patients may not fully understand or comprehend all that is said to them. The use of audiotaping consultations has been studied in some settings, but not in head and neck cancer clinics. We report on a series of 50 consecutive head and neck patients to determine their views on the value of this facility. Thirty-nine patients (78 per cent) utilized the opportunity, of which 36 patients (92 per cent) found it beneficial. Over three quarters of the patients who used the facility thought that medical staff could benefit and learn from the tape recording. We recommend that audiotaping becomes a standard part of the multidisciplinary head and neck oncology clinic, helping to improve the overall quality of patient care.

Objective: Measurement of voluntary activation gives an indication of neural drive to the muscle. This study aimed to identify the site of impairment in neural drive during voluntary contractions post-stroke. Methods: Elbow-flexor voluntary activation was assessed bilaterally for 10 stroke patients (mean 61.2 ± 12.3 years) and 6 age-matched controls (61.3 ± 14.0 years) by stimulating either the peripheral nerve or the motor cortex during maximal voluntary contractions. Any additional evoked force during maximal contractions implies neural drive is incomplete. Peripheral stimulation can detect deficits at or above the stimulation level, while cortical stimulation can identify suboptimal supraspinal output. Results: Impairments were apparent on the less-affected side in addition to the more-affected side after stroke in voluntary activation, torque, and electromyographic activity (EMG) response. Maximal torque was reduced by 44% on the more-affected and 31% on the less-affected side compared to healthy controls (p

Cross-sectional descriptive study of randomised controlled trials involving physical interventions for people with spinal cord injury (SCI) published between 2003 and 2013. To determine how well randomised controlled trials of physical interventions for people with SCI adhere to the CONSORT (Consolidated Standards of Reporting Trials) guidelines. University of Sydney, Sydney, NSW, Australia. A search was conducted for randomised controlled trials designed to determine the effectiveness of physical interventions for people with SCI published between 2003 and 2013. The CONSORT checklist for the reporting of randomised controlled trials was used to determine how well each trial adhered to the guidelines. Two independent reviewers rated each trial on each of the 37 items on the CONSORT checklist using the following criteria: ‘fully reported’, ‘partially reported’, ‘not reported’, ‘not relevant’ or ‘not reported but unable to determine if relevant/done’. Fifty-three trials were retrieved. None of the trials ‘fully reported’ all items of the CONSORT guidelines. The median (IQR) number of items that was ‘fully reported’ was 11/37 (7–20). The median (IQR) number of items that was either ‘fully reported’ or ‘not relevant’ or ‘not reported but unable to determine if relevant’ was 20/37 items (17–27). The reporting of randomised controlled trials in SCI is only partially adhering to the CONSORT guidelines. Journals can help lift standards by encouraging authors of randomised controlled trials to adhere to the CONSORT guidelines.

Chronic benign pleural effusion (BPE) is a rare complication of concurrent chemoradiotherapy (CRT) for inoperable stage IIIA non-small-cell lung cancer (NSCLC). This report presents three cases of BPE, the workup to differentiate this benign condition from recurrence of cancer and recommends a pleural biopsy as part of the diagnostic process. These inflammatory exudates often remain indolent, and may not require drainage or surgical intervention. In the absence of clinical, radiological and pathological evidence of recurrent disease, we recommend clinicians manage these patients expectantly, using regular clinical assessment and imaging.

Molecular characterisation of non-squamous non-small-cell lung cancer (NSCLC) is required to direct optimal treatment. Treatment of NSCLC with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (EGFR-TKI) should be guided by the presence of activating mutations of the EGFR gene.To gain insight into the rate of testing, the range of tissues samples, test utility and outcome when cost of testing as a barrier to access is removed in the Australian setting.In October 2010, a sponsored programme was commenced to gather data on EGFR gene mutation testing in Australia. Partnering laboratories were funded for provision of de-identified results. For participating patients, the programme supported the test charge. Mutation testing was performed using Sanger sequencing of exons 18-21 of the EGFR.Samples 2013 were submitted from 2012 patients. Full sequencing was achieved in 1717 (85%). Failure of full sequencing was more likely in samples derived from fine needle aspiration(FNA) biopsy than tissue biopsy or pleural/pericardial fluid cell blocks OR 3.1 (95% CI 1.9-5.2). There were 359 mutations seen in 337 patients. 14.5% of cases had a classical mutation conferring sensitivity to EGFR-TKI. In addition there was a range of less common mutations - some predicting responses and others of uncertain significance. 1.4% of cases had mutations associated with non-responsiveness to EGFR-TKI.EGFR gene mutation testing is feasible on local and interstate lung cancer samples. The rate of valid test outcomes is high, but FNA samples are associated with more frequent test failure.

Monoclonal antibodies, directed against a 58-kDa Babesia bigemina merozoite antigen that reacted strongly with immune sera from experimentally and naturally infected cattle in Western blots, were used to develop a competitive-inhibition enzyme-linked immunosorbent assay (ELISA). As based on the testing of 70 antibody-positive sera from experimentally infected cattle and 166 antibody-negative sera collected in non-endemic areas of Australia, the sensitivity and specificity of the ELISA were 95.7% and 97.0%, respectively. In sequential sera collected from six calves during the course of experimental B. bigemina infections the ELISA detected seroconversion at about 10 days post-inoculation. The specificity of the ELISA was not affected by the presence of antibodies to B. bovis, Anaplasma marginale or Theileria buffeli. In 42 sera from cattle experimentally infected with B. bovis but negative for B. bigemina the specificity of the ELISA was 95.2%. The use of a competitive-inhibition ELISA format detecting only antibody directed against a single epitope on the 58-kDa antigen appears to have overcome many of the specificity problems that have plagued serological tests for B. bigemina in the past. The test should be useful for epidemiology studies, particularly in areas where B. bovis and B. bigemina have overlapping distributions.

APSIM-wheat is a crop system simulation model, consisting of modules that incorporate aspects of soil water, nitrogen (N), residues, and crop development. The model was used to simulate above- and belowground growth, grain yield, water and N uptake, and soil water and soil N in wheat crops in Western Australia. Model outputs were compared with detailed field experiments from four rainfall zones, three soil types, and five wheat genotypes. The field experiments covered 10 seasons, with variations in sowing date, plant density, N fertiliser, deep ripping and irrigation. The overall APSIM model predictions of shoot growth, root depth, water and N uptake, soil water, soil N, drainage and nitrate leaching were found to be acceptable. Grain yields were well predicted with a coefficient of determination r2(1:1)=0.77, despite some underestimation during severe terminal droughts. Yields tended to be underestimated during terminal droughts due to insufficient pre-anthesis stored carbohydrates being remobilised to the grain. Simulation of grain protein, and depth to the perched water table showed limited accuracy when compared with field measurements. In particular, grain protein tended to be overpredicted at high protein levels and underpredicted at low levels. However, specific simulation studies to predict biomass, yield, drainage and nitrate leaching are now possible for wheat crops on the tested soil types and rainfall zones in Western Australia.