Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation.

Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. High-affinity cells are proposed to preferentially select into this compartment, potentiating the immune response. We used single-cell RNA-seq to track the germinal center (GC) development of Ighg2A10 B cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites, we identified 3 populations of cells in the GC light zone (LZ). One LZ population expressed a gene signature associated with the initiation of PC differentiation and readily formed PCs in vitro. The estimated affinity of these pre-PC B cells was indistinguishable from that of LZ cells that remained in the GC. This remained true when high- or low-avidity recombinant PfCSP proteins were used as immunogens. These findings suggest that the initiation of PC development occurs via an affinity-independent process.

Early T Cell Infiltration Correlates with Anti-CTLA4 Treatment Response in Murine Cancer Models.

Immune checkpoint inhibitor (ICI) Abs are a revolutionary class of cancer treatment, but only ∼30% of patients receive a lasting benefit from therapy. Preclinical studies using animals from the same genetic backgrounds, challenged with the same cancer models, also show nonuniform responses. Most mouse studies that have evaluated tumor-infiltrating leukocytes after ICI therapy cannot directly correlate their findings with treatment outcomes, because terminal methods were used to acquire immune infiltrate data. In the present study, we used fine-needle aspiration (a nonterminal sampling method) to collect multiple aspirates over several days from s.c. implanted P815, CT26, and 4T1 mouse cancer models treated with ICI Abs. These aspirates were then analyzed with flow cytometry to directly correlate tumor-infiltrating leukocyte populations with treatment success. We found that the P815 and CT26 models respond well to anti-CTLA4 therapies. Among P815-challenged animals, mice that regressed following anti-CTLA4 treatment showed significant increases in CD8+ T cells on days 3, 5, and 7 and in CD4+ T cells on days 5 and 7 and a decrease in macrophages and monocytes on days 3, 5, and 7 after treatment. Similar results were obtained in the CT26 model on day 11 posttreatment. Our study is the first, to our knowledge, to directly correlate early tumor infiltration of T cells with anti-CTLA4 treatment success, thus providing a mechanistic clue toward understanding why alloidentical mice challenged with identical tumors do not respond uniformly to ICI therapies.

Plasticity in branch water relations and stem hydraulic vulnerability enhances hydraulic safety in mangroves growing along a salinity gradient.

Coping with water stress depends on maintaining cellular function and hydraulic conductance. Yet measurements of vulnerability to drought and salinity do not often focus on capacitance in branch organs that buffer hydraulic function during water stress. The relationships between branch water relations, stem hydraulic vulnerability and stem anatomy were investigated in two co-occurring mangroves Aegiceras corniculatum and Rhizophora stylosa growing at low and high salinity. The dynamics of branch water release acted to conserve water content in the stem at the expense of the foliage during extended drying. Hydraulic redistribution from the foliage to the stem increased stem relative water content by up to 21%. The water potentials at which 12% and 50% loss of stem hydraulic conductivity occurred decreased by ~1.7 MPa in both species between low and high salinity sites. These coordinated tissue adjustments increased hydraulic safety despite declining turgor safety margins at higher salinity sites. Our results highlight the complex interplay of plasticity in organ-level water relations with hydraulic vulnerability in the maintenance of stem hydraulic function in mangroves distributed along salinity gradients. These results emphasise the importance of combining water relations and hydraulic vulnerability parameters to understand vulnerability to water stress across the whole plant.

The Role of DNA Methylation in Genome Defense in Cnidaria and Other Invertebrates.

Considerable attention has recently been focused on the potential involvement of DNA methylation in regulating gene expression in cnidarians. Much of this work has been centered on corals, in the context of changes in methylation perhaps facilitating adaptation to higher seawater temperatures and other stressful conditions. Although first proposed more than 30 years ago, the possibility that DNA methylation systems function in protecting animal genomes against the harmful effects of transposon activity has largely been ignored since that time. Here, we show that transposons are specifically targeted by the DNA methylation system in cnidarians, and that the youngest transposons (i.e., those most likely to be active) are most highly methylated. Transposons in longer and highly active genes were preferentially methylated and, as transposons aged, methylation levels declined, reducing the potentially harmful side effects of CpG methylation. In Cnidaria and a range of other invertebrates, correlation between the overall extent of methylation and transposon content was strongly supported. Present transposon burden is the dominant factor in determining overall level of genomic methylation in a range of animals that diverged in or before the early Cambrian, suggesting that genome defense represents the ancestral role of CpG methylation.

Compression Therapy to Prevent Recurrent Cellulitis of the Leg.

BACKGROUND: Chronic edema of the leg is a risk factor for cellulitis. Daily use of compression garments on the leg has been recommended to prevent the recurrence of cellulitis, but there is limited evidence from trials regarding its effectiveness. METHODS: In this single-center, randomized, nonblinded trial, we assigned participants with chronic edema of the leg and recurrent cellulitis, in a 1:1 ratio, to receive leg compression therapy plus education on cellulitis prevention (compression group) or education alone (control group). Follow-up occurred every 6 months for up to 3 years or until 45 episodes of cellulitis had occurred in the trial. The primary outcome was the recurrence of cellulitis. Participants in the control group who had an episode of cellulitis crossed over to the compression group. Secondary outcomes included cellulitis-related hospital admission and quality-of-life assessments. RESULTS: A total of 183 patients were screened, and 84 were enrolled; 41 participants were assigned to the compression group, and 43 to the control group. At the time of a planned interim analysis, when 23 episodes of cellulitis had occurred, 6 participants (15%) in the compression group and 17 (40%) in the control group had had an episode of cellulitis (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.59; P = 0.002; relative risk [post hoc analysis], 0.37; 95% CI, 0.16 to 0.84; P = 0.02), and the trial was stopped for efficacy. A total of 3 participants (7%) in the compression group and 6 (14%) in the control group were hospitalized for cellulitis (hazard ratio, 0.38; 95% CI, 0.09 to 1.59). Most quality-of-life outcomes did not differ between the two groups. No adverse events occurred during the trial. CONCLUSIONS: In this small, single-center, nonblinded trial involving patients with chronic edema of the leg and cellulitis, compression therapy resulted in a lower incidence of recurrence of cellulitis than conservative treatment. (Funded by Calvary Public Hospital Bruce; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000412336.).

Ghosts of dry seasons past: Legacy of severe drought enhances mangrove salinity tolerance through coordinated cellular osmotic and elastic adjustments.

The incidence and severity of global mangrove mortality due to drought is increasing. Yet, little is understood of the capacity of mangroves to show long-term acclimation of leaf water relations to severe drought. We tested for differences between mid-dry season leaf water relations in two cooccurring mangroves, Aegiceras corniculatum and Rhizophora stylosa before a severe drought (a heatwave combined with low rainfall) and after its relief by the wet season. Consistent with ecological stress memory, the legacy of severe drought enhanced salinity tolerance in the subsequent dry season through coordinated adjustments that reduced the leaf water potential at the turgor loss point and increased cell wall rigidity. These adjustments enabled maintenance of turgor and relative water content with increasing salinity. As most canopy growth occurs during the wet season, acclimation to the 'memory' of higher salinity in the previous dry season enables greater leaf function with minimal adjustments, as long-lived leaves progress from wet through dry seasons. However, declining turgor safety margins - the difference between soil water potential and leaf water potential at turgor loss - implied increasing limitation to water use with increasing salinity. Thus, plasticity in leaf water relations contributes fundamentally to mangrove function under varying salinity regimes.

New insights from modelling studies and molecular dynamics simulations of the DIS5-S6 extracellular linker of the skeletal muscle sodium channel NaV1.4.

In the CryoEM-structure of the hSkMNaV1.4 ion channel (PDB:6AGF), the 59-residue DIS5-S6 linker peptide was omitted due to absence of electron density. This peptide is intriguing - comprised of unique sequence and found only in mammalian skeletal muscle sodium ion channels. To probe potential physiological and evolutionary significance, we constructed an homology model of the complete hSkMNaV1.4 channel. Rather than a flexible random coil potentiating drift across the channel, the linker folds into a compact configuration through self-assembling secondary structural elements. Analogous sequences from 48 mammalian organisms show hypervariability with between 40% and 100% sequence similarity. To investigate structural implications, sequences from 14 representative organisms were additionally modelled. All showed highly conserved N-and C-terminal residues closely superimposed, suggesting a critical functional role. An optimally located asparagine residue within the conserved region was investigated for N-linked glycosylation and MD simulations carried out. Results suggest a complex glycan added at this site in the linker may form electrostatic interactions with the DIV voltage sensing domain and be mechanistically involved in channel gating. The relationship of unique sequence, compact configuration, potential glycosylation and MD simulations are discussed relative to SkMNaV1.4 structure and function.

The Effect of Scale Insects on Growth Parameters of cv. Chardonnay and cv. Sauvignon Blanc Grapevines Grown in a Greenhouse.

Plants can respond to insects that feed with stylet mouthparts using various processes that are initiated via the salicylic acid metabolic pathway. In Australia, scale insects of the genus Parthenolecanium can cause economic damage to grapevines as they feed on the vines and produce honeydew as a waste by-product, which supports the growth of black sooty mould on fruit and leaves, potentially affecting the plant growth and yield. Using rootlings of Sauvignon Blanc (SB, resistant) and Chardonnay (Char, susceptible), the growth and production of volatile organic compounds (VOCs) following exposure to scale insect infestations were measured under controlled greenhouse conditions. At harvest, the numbers of scale insects per five leaves were higher on plants infested at the start of the study compared with the control plants. Infested SB had increased dry root and shoot mass compared with the SB control, which was also the case with Char (control and infested). Leaf volatiles differed between cultivars in response to scale infestation. Benzyl alcohol decreased among infested SB plants compared with the other treatments. A change in the salicylic acid pathway as indicated by the change in benzyl alcohol may cause the increased growth in SB associated with the increased scale insect infestation.

Does mechanical threshold inspiratory muscle training promote recovery and improve outcomes in patients who are ventilator-dependent in the intensive care unit? The IMPROVE randomised trial.

BACKGROUND: In patients who are ventilator-dependent in the intensive care unit, inspiratory muscle training may improve inspiratory muscle strength and accelerate liberation from the ventilator, but optimal training parameters are yet to be established, and little is known about the impact of inspiratory muscle training on quality of life or dyspnoea. Thus, we sought to ascertain whether inspiratory muscle training, commenced while ventilator-dependent, would improve outcomes for patients invasively ventilated for 7 days or longer. METHODS: In this randomised trial with assessor blinding and intention-to-treat analysis, 70 participants (mechanically ventilated ≥7 days) were randomised to receive once-daily supervised high-intensity inspiratory muscle training with a mechanical threshold device in addition to usual care or to receive usual care (control). Primary outcomes were inspiratory muscle strength (maximum inspiratory pressure % predicted) and endurance (fatigue resistance index) at ventilator liberation and 1 week later. Secondary outcomes included quality of life (SF-36v2, EQ-5D), dyspnoea, physical function, duration of ventilation, and in-hospital mortality. RESULTS: Thirty-three participants were randomly allocated to the training group, and 37 to the control group. There were no statistically significant differences in strength (maximum inspiratory pressure) (95% confidence interval [CI]: -7.4 to 14.0) or endurance (fatigue resistance index) (95% CI: -0.003 to 0.436). Quality of life improved significantly more in the training group than in the control group (EQ-5D: 17.2; 95% CI: 1.3-33.0) (SF-36-PCS: 6.97; 95% CI: 1.96-12.00). Only the training group demonstrated significant reductions in dyspnoea (-1.5 at rest, -1.9 during exercise). There were no between-group differences in duration of ventilation or other measures. In-hospital mortality was higher in the control group than in the training group (9 vs 4, 24% vs 12%, p = 0.23). CONCLUSIONS: In patients who are ventilator-dependent, mechanical threshold loading inspiratory muscle training improves quality of life and dyspnoea, even in the absence of strength improvements or acceleration of ventilator liberation.

A Dual-Antigen Enzyme-Linked Immunosorbent Assay Allows the Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in a Low-Transmission Setting.

Estimates of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been hampered by inadequate assay sensitivity and specificity. Using an enzyme-linked immunosorbent assay-based approach that combines data about immunoglobulin G responses to both the nucleocapsid and spike receptor binding domain antigens, we show that excellent sensitivity and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies in a cohort of elective surgery patients in Australia and estimated seroprevalence in Australia to be 0.28% (95% Confidence Interval, 0-1.15%). These data confirm the low level of transmission of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay.

Repeatability of lateralisation in mosquitofish Gambusia holbrooki despite evidence for turn alternation in detour tests.

Akin to handedness in humans, some animals show a preference for moving to the left or right. This is often attributed to lateralised cognitive functions and eye dominance, which, in turn, influences their behaviour. In fishes, behavioural lateralisation has been tested using detour mazes for over 20 years. Studies report that certain individuals are more likely to approach predators or potential mates from one direction. These findings imply that the lateralisation behaviour of individuals is repeatable, but this is rarely confirmed through multiple testing of each individual over time. Here we quantify the repeatability of turning behaviour by female mosquitofish (Gambusia holbrooki) in a double sided T-maze. Each female was tested three times in each of six treatments: when approaching other females, males, or an empty space; and when able to swim freely or when forced to choose by being herded from behind with a net. Although there was no turning bias based on the mean population response, we detected significant repeatability of lateralisation in five of the six treatments (R = 0.251-0.625). This is noteworthy as we also found that individuals tended to alternate between left and right turns, meaning that they tend to move back and forth along one wall of the double-sided T-maze. Furthermore, we found evidence for this wall following when re-analysing data from a previous study. We discuss potential explanations for this phenomenon, and its implications for study design.

Musculoskeletal Injury in Paddle Sport Athletes.

INTRODUCTION: Kayak racing has been an Olympic sport since 1936. The sport is evolving with the introduction of ocean skis and stand-up-paddle boards (SUP). Musculoskeletal injury incidence surveys have been conducted for ultra-marathon events, but no data have been published for other racing formats. OBJECTIVE: To identify and compare the rates and types of injuries sustained by paddling athletes as a function of discipline and training parameters in Sprint, Marathon, Ultra-Marathon, and Ocean events. METHODS: Competitors from 6 kayak and/or ocean surf-ski races in Australia were surveyed. Before each race, competitors were asked to complete a questionnaire. The questionnaire investigated paddling-related injuries over the previous 5 years, athlete morphology, flexibility, equipment and its setup, training volume, and environment. RESULTS: Five hundred eighty-three competitors were surveyed. Disciplines included 173 racing-kayak (K1), 202 touring-kayak, 146 ocean-skis, 42 SUP, and 20 other. The top 5 paddling-related injuries were shoulder (31%), low back (23.5%), wrist (16.5%), neck (13.7%), and elbow (11.0%). The highest percentage of injury was found in K1 paddlers for shoulder (40.5%), SUP for low back (33.3%), and ocean-ski for wrist (22.6%). After controlling for on-water training hours, the relative risk (RR) of wrist injury was significantly increased in ocean-ski paddlers (1.86) and in paddlers with decreased flexibility (1.53-1.83). Relative risk of shoulder and low-back injury was significantly increased in athletes with lower training volumes (1.82-2.07). Younger athletes had lower RR of wrist and shoulder injury (0.58-0.62).

Total volume of cam deformity alone predicts outcome in arthroscopy for femoroacetabular impingement.

PURPOSE: Rates for arthroscopic surgery for femoroacetabular impingement (FAI) are rising and there is growing concern related to the effectiveness and costs associated with this treatment. There is a general lack of consensus as to the criteria for surgical selection of patients. The purpose of this study was to determine whether patient outcome following arthroscopic surgery for FAI could be predicted based on the size and location of deformity. The specific questions were: (1) what is the morphology of FAI in terms of size and location of deformity in a cohort of patients selected for surgery? (2) Do morphological factors predict postoperative improvement in hip scores? (3) Do morphological factors predict preoperative hip scores? (4) Are there clusters of morphological factors which explain postsurgical improvement in hip scores? MATERIALS AND METHODS: Computer tomography (CT) surgical plans of 90 hips in 79 patients who had undergone primary hip arthroscopy for FAI were retrospectively reviewed. Four parameters for the femur and acetabulum were created: total depth of deformity, maximal depth, extent and the position of maximal deformity. This data were compared with prospectively acquired preoperative and postoperative patient outcome data using generalised linear models. RESULTS: The cohort comprised 33 males and 46 females aged 37.9 (18-61). The majority (74%) had mixed morphology, 23% isolated cam, and 3% isolated pincer. Overall, the bone depth was greatest and more extensive on the femur. Increased total additional cam deformity alone predicted poorer postoperative outcome (p = 0.045). None of the morphological factors were related to preoperative scores and there was no association between the meta-variables and postoperative outcome. CONCLUSIONS: The results of this study indicate that a greater total volume of cam deformity led to poorer postoperative patient outcome scores at 1 year. This information provides the surgeon with more accurate patient-specific data for prediction of expected outcomes. LEVEL OF EVIDENCE: Level III diagnostic.

Faecal calprotectin testing for identifying patients with organic gastrointestinal disease: systematic review and meta-analysis.

OBJECTIVES: To assess the clinical effectiveness of faecal calprotectin (FC) testing for distinguishing between organic gastrointestinal diseases (organic GID), such as inflammatory bowel disease (IBD), and functional gastrointestinal disorders (functional GIDs). STUDY DESIGN: Studies that assessed the accuracy of FC testing for differentiating between IBD or organic GID and functional GIDs were reviewed. Articles published in English during January 1998 - June 2018 that compared diagnostic FC testing in primary care and outpatient hospital settings with a reference test and employed the standard enzyme-linked immunosorbent FC assay method with a cut-off of 50 or 100 µg/g faeces were included. Study quality was assessed with QUADAS-2, an evidence-based quality assessment tool for diagnostic accuracy studies. DATA SOURCES: MEDLINE and EMBASE; reference lists of screened articles. DATA SYNTHESIS: Eighteen relevant studies were identified. For distinguishing patients with organic GID (including IBD) from those with functional GIDs (16 studies), the estimated sensitivity of FC testing was 81% (95% CI, 74-86%), the specificity 81% (95% CI, 71-88%); area under the curve (AUC) was 0.87. For distinguishing IBD from functional GIDs (ten studies), sensitivity was 88% (95% CI, 80-93%), specificity 72% (95% CI, 59-82%), and AUC 0.89. Assuming a population prevalence of organic GID of 1%, the positive predictive value was 4.2%, the negative predictive value 100%. The difference in sensitivity and specificity between FC testing cut-offs of 50 µg/g and 100 µg/g faeces was not statistically significant (P = 0.77). CONCLUSIONS: FC testing is clinically useful for distinguishing organic GID (including IBD) from functional GIDs, and its incorporation into clinical practice for evaluating patients with lower gastrointestinal symptoms could lead to fewer patients with functional GIDs undergoing colonoscopy, reducing costs for both patients and the health system. PROSPERO REGISTRATION: CRD4201810507.

Mobilisation is feasible in intensive care patients receiving vasoactive therapy: An observational study.

BACKGROUND: Mobilisation of intensive care unit (ICU) patients reduces ICU-acquired weakness and is associated with better functional outcomes. However, the prevalence of mobilisation of ICU patients remains low. A known barrier to mobilisation is haemodynamic instability, frequently with patients requiring vasoactive therapy. There is a lack of published data to guide clinicians about the safety and feasibility of mobilising patients receiving vasoactive therapy. OBJECTIVES: To describe our mobilisation practice in ICU patients receiving vasoactive therapy and identify factors associated with mobilisation and adverse events. METHODS: Retrospective cohort study of patients undergoing vasoactive therapy in a 31-bed tertiary ICU (October-December, 2016). Details of vasoactive drug dosage, mobilisation, and adverse events were extracted from databases, including mobilisation intensity (ICU Mobility Scale [IMS]). Two generalised linear mixed models were used: first, to describe factors associated with mobilisation and second, to describe factors associated with adverse events during mobilisation, adjusting for age, gender, and acute physiology and chronic health evaluation II score as co-variates. RESULTS: In 119 patients undergoing vasoactive therapy on 371 cumulative vasoactive days, 195 mobilisation episodes occurred (37.5% of vasoactive days). Low (76.8%) and moderate (13.7%) dose vasoactive therapies were associated with a higher probability of mobilisation relative to high (9.4%) dose therapy (odds ratio = 5.50, 95% confidence interval = 2.23-13.59 and odds ratio = 2.50, 95% confidence interval = 0.95-6.59, respectively). For patients who mobilised on vasoactive therapy (n = 72), maximum mobilisation intensity was low (IMS = 1-2) in 31%, moderate (IMS = 3-5) in 51%, and high (IMS = 6-10) in 18% of vasoactive days. While no serious adverse events occurred, there were 14 occurrences of reversible hypotension requiring transient escalation of vasoactive therapy (7.3%), associated with lower mean arterial pressure (p = 0.001). CONCLUSION: In our ICU, patients mobilised on approximately one-third of vasoactive days. Clinicians should anticipate a higher risk of hypotension during mobilisation in patients receiving vasoactive therapy, which may require transient escalation of vasoactive therapy.

Breast surgery for metastatic breast cancer.

BACKGROUND: Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question. OBJECTIVES: To assess the effects of breast surgery in women with metastatic breast cancer. SEARCH METHODS: We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. MAIN RESULTS: We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence). AUTHORS' CONCLUSIONS: Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.

Asking the difficult questions: Building the capacity of community paediatricians to routinely enquire and respond to family violence.

AIM: To enhance the confidence and capacity of community paediatricians and paediatric trainees to identify and respond to family violence, through a series of education sessions and evidence-based recommendations. METHODS: The action research methodology included a literature search to review the data on family violence education programmes and evidence-based family violence screening tools. Six education sessions were then developed and held for physicians at the Community Paediatric and Child Health Service (CPCHS). An audit was performed on the charts of all new referrals to the CPCHS for a period of 18 months prior to the education sessions and 5 months following the education sessions. A questionnaire was distributed at the first and final education sessions to gauge physician comfort with enquiry into family violence. RESULTS: The documented rate of enquiry into family violence at CPCHS was 24% in the retrospective chart audit. Following the series of education sessions, the documented rate of enquiry increased to 60% (P < 0.05, odds ratio 4.7, confidence interval 2.7-8.4). The documented rate of disclosure of family violence also increased from 13% of all new patients in the retrospective chart audit to 24% in the prospective arm of the study (P < 0.05, odds ratio 2.1, confidence interval 1.0-4.0). Following the education sessions, all participants agreed that they routinely enquired about family violence and were comfortable enquiring about family violence. CONCLUSION: This study demonstrates that clinician education about family violence supports routine enquiry about family violence in community paediatric consultations.

Place of death in the Snowy Monaro region of New South Wales: A study of residents who died of a condition amenable to palliative care.

OBJECTIVE: To describe the place of death of residents in a rural region of New South Wales. DESIGN: Cross-sectional quantitative study using death data collected from local funeral directors (in person and websites), residential aged-care facilities, one multipurpose heath service and obituary notices in the local media (newspapers/radio). SETTING: Snowy Monaro region (New South Wales Australia). PARTICIPANTS: Residents, with advanced frailty or one of 10 conditions amenable to palliative care, who died between 1 February 2015 and 31 May 2016. MAIN OUTCOME MEASURE: Place of death. RESULTS: Of 224 deaths in this period, 138 were considered amenable to palliative care. Twelve per cent of these deaths occurred in a private residence, 38% in the usual place of residence and 91% within the region. CONCLUSION: Most rural residents with conditions amenable to palliative care died in the region. Most did not die in their usual place of residence. Further qualitative work is needed to determine palliative care patients' and family caregivers' preferences for, and the importance placed on, place of death. While there may be a need to support an increase in home deaths, local rural hospitals and residential aged-care facilities must not be overlooked as a substitute for inpatient hospices.

Supervised or Unsupervised Rehabilitation After Total Hip Replacement Provides Similar Improvements for Patients: A Randomized Controlled Trial.

OBJECTIVE: To determine whether patients do better with unsupervised (home-based) physiotherapy or in an outpatient setting. SETTING: Acute care public hospital in the region, supporting a population of ∼540,000. DESIGN: Single-blind randomized controlled trial. PARTICIPANTS: Adult patients (N=98) after unilateral elective total hip replacement (THR) were randomly assigned to a supervised (center-based) exercise (n=56) or a unsupervised (home-based) exercise (n=42) program and followed for 6 months postsurgery. INTERVENTIONS: The supervised group attended a 4-week outpatient rehabilitation program supervised by a physiotherapist. The unsupervised group was given written and pictorial instructions to perform rehabilitation independently at home. MAIN OUTCOME MEASURES: Western Ontario and McMaster Universities Osteoarthritis Index; Short-Form 36-item Health Questionnaire (SF-36) mental and physical component summary measures; University of California, Los Angeles activity scale; and timed Up and Go test. RESULTS: There were no differences between the groups for any measure. The overall differences between the adjusted means were as follows: Western Ontario and McMaster Universities Osteoarthritis Index, 0.50 (95% confidence interval [CI], -6.8 to 5.7); SF-36 physical component summary, 0.8 (95% CI, -6.5 to 8.1); SF-36 mental component summary, 1.7 (95% CI, -4.1 to 7.4); University of California, Los Angeles activity scale, 0.3 (95% CI, 5.2 to 6.1); and timed Up and Go test, 0 seconds (95% CI, -1.4 to 1.3s). CONCLUSIONS: The results demonstrated that outcomes in response to rehabilitation after THR are clinically and statistically similar whether the program was supervised or not. The results suggest that early rehabilitation programs can be effectively delivered unsupervised in the home to low-risk patients discharged home after THR. However, the relative effect of late-stage rehabilitation was not tested.

Understanding barriers to fruit and vegetable intake in the Australian Longitudinal Study of Indigenous Children: a mixed-methods approach.

OBJECTIVE: To identify barriers to fruit and vegetable intake for Indigenous Australian children and quantify factors related to these barriers, to help understand why children do not meet recommendations for fruit and vegetable intake. DESIGN: We examined factors related to carer-reported barriers using multilevel Poisson models (robust variance); a key informant focus group guided our interpretation of findings. SETTING: Eleven diverse sites across Australia. SUBJECTS: Australian Indigenous children and their carers (N 1230) participating in the Longitudinal Study of Indigenous Children. RESULTS: Almost half (45 %; n 555/1230) of carers reported barriers to their children's fruit and vegetable intake. Dislike of fruit and vegetables was the most common barrier, reported by 32·9 % of carers; however, we identified few factors associated with dislike. Carers were more than ten times less likely to report barriers to accessing fruit and vegetables if they lived large cities v. very remote areas. Within urban and inner regional areas, child and carer well-being, financial security, suitable housing and community cohesion promoted access to fruit and vegetables. CONCLUSIONS: In this national Indigenous Australian sample, almost half of carers faced barriers to providing their children with a healthy diet. Both remote/outer regional carers and disadvantaged urban/inner regional carers faced problems accessing fruit and vegetables for their children. Where vegetables were accessible, children's dislike was a substantial barrier. Nutrition promotion must address the broader family, community, environmental and cultural contexts that impact nutrition, and should draw on the strengths of Indigenous families and communities.