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Introduction Adolescent e-cigarette use, globally and within Australia, has increased in recent years. In response, public health agencies have called for the development of education and communication programmes targeting adolescents. Despite such recommendations, few rigorous evaluations of such interventions currently exist. The main objective of this study is to examine the potential effect of a text message intervention targeting parents and adolescents on adolescent susceptibility to e-cigarette use (eg, intentions towards using e-cigarettes). Secondary objectives are to (1): examine the effect of the intervention on adolescent e-cigarette and combustible tobacco use and (2) examine the acceptability of the intervention.Methods and analysis A randomised controlled trial employing a 2×2 factorial design will be conducted with parent–adolescent dyads (aged 12–15 years). Dyads will be randomly allocated to one of four arms: arm 1—a text message intervention delivered to adolescents only; arm 2—a text message intervention delivered to the parents of adolescents only; arm 3—a text message intervention delivered to both the parents and adolescents; and arm 4—an information only control, consisting of an e-cigarette factsheet provided to parents only. Participant recruitment commenced in March 2023 with the aim to recruit 120 parent–adolescent dyads. Data collection to assess study outcomes will occur at baseline, 6, 12 and 24 months post the commencement of the intervention. The primary endpoint will be 6-month follow-up. The primary outcome will be adolescent susceptibility to e-cigarette use, assessed using validated items. Analyses of trial outcomes will be undertaken under an intention-to-treat framework, with all participants included in the analysis in the group they were allocated.Ethics and dissemination Ethics approval has been obtained from the human research ethics committee of the University of Newcastle (H-2022-0340). Findings will be disseminated in peer-reviewed journals and at conferences.Trial registration number The trial was registered prospectively with Australian New Zealand Clinical Trials Registry (ACTRN12623000079640).

Background OptiBreech collaborative care is a multi-disciplinary care pathway for breech presentation at term. The OptiBreech Multiple Trial Cohort is designed to host multiple trials related to care for breech presentation. This design enables prospective data collection for a large cohort of women planning a vaginal breech birth (VBB), to assess rare safety outcomes, while answering questions requiring a smaller, randomised sample nested within this cohort. Methods OptiBreech database currently contains participants recruited from 10 January 2022, including 67 women randomised to either OptiBreech care or standard care, and 116 women who received OptiBreech care and were not randomised. Primary outcomes included vaginal birth rate, composite neonatal morbidity and mortality and composite maternal neonatal morbidity and mortality. Descriptive statistics for the entire cohort were analysed in SPSS Version 29. Sub-group analyses were identified through participant involvement and engagement work as important to support informed decision-making. Results Of 97 women who planned a VBB at any point, 44 (45.4%) achieved a vaginal birth, compared to 29/77 (37.7%) of women who did not plan a VBB. Admission rates to a neonatal unit were similar, 4/97 (4.1%) versus 3/77 (3.9%). In this cohort, there was no severe neonatal morbidity following planned VBB, compared to 3/77 (3.9%) among the cohort who did not plan a vaginal breech birth and 2/52 (3.7%) among women who planned a cephalic birth. Severe maternal morbidity following planned VBB was 7/89 (7.9%), compared to 9/76 (11.8%) for women who did not plan a VBB and 8/54 (14.8%) for women who planned a cephalic birth. Conclusions Planning a VBB with OptiBreech collaborative care has thus far been as safe as not planning a VBB. Detecting differences in rare outcomes will require thousands of births. Outcomes will continue to be monitored and reported here as the cohort grows.

Background While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. Methods We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. Results Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42–1.64, for urban-adjacent rural and 1.65, 1.42–1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02–1.12) and high (1.33, 1.23–1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27–1.43) but not medium vaccination rates (1.00, 0.95–1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. Conclusions Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

Background The COVID-19 pandemic has demonstrated the need for efficient and comprehensive, simultaneous assessment of multiple combined novel therapies for viral infection across the range of illness severity. Randomized Controlled Trials (RCT) are the gold standard by which efficacy of therapeutic agents is demonstrated. However, they rarely are designed to assess treatment combinations across all relevant subgroups. A big data approach to analyzing real-world impacts of therapies may confirm or supplement RCT evidence to further assess effectiveness of therapeutic options for rapidly evolving diseases such as COVID-19. Methods Gradient Boosted Decision Tree, Deep and Convolutional Neural Network classifiers were implemented and trained on the National COVID Cohort Collaborative (N3C) data repository to predict the patients’ outcome of death or discharge. Models leveraged the patients’ characteristics, the severity of COVID-19 at diagnosis, and the calculated proportion of days on different treatment combinations after diagnosis as features to predict the outcome. Then, the most accurate model is utilized by eXplainable Artificial Intelligence (XAI) algorithms to provide insights about the learned treatment combination impacts on the model’s final outcome prediction. Results Gradient Boosted Decision Tree classifiers present the highest prediction accuracy in identifying patient outcomes with area under the receiver operator characteristic curve of 0.90 and accuracy of 0.81 for the outcomes of death or sufficient improvement to be discharged. The resulting model predicts the treatment combinations of anticoagulants and steroids are associated with the highest probability of improvement, followed by combined anticoagulants and targeted antivirals. In contrast, monotherapies of single drugs, including use of anticoagulants without steroid or antivirals are associated with poorer outcomes. Conclusions This machine learning model by accurately predicting the mortality provides insights about the treatment combinations associated with clinical improvement in COVID-19 patients. Analysis of the model’s components suggests benefit to treatment with combination of steroids, antivirals, and anticoagulant medication. The approach also provides a framework for simultaneously evaluating multiple real-world therapeutic combinations in future research studies.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

Behaviour change technique (BCT) taxonomies provide one approach to unpack the complexity of childhood obesity prevention interventions. This scoping review sought to examine how BCT taxonomies have been applied to understand childhood obesity prevention interventions targeting children aged 12 years or under and/or their caregivers. A systematic search was conducted in Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and PROSPERO, to capture all eligible research up to February 2021. No limits were placed on country, language, publication dates, or full text availability. Eligible studies included any study design that applied a BCT taxonomy and evaluated behavioural childhood obesity prevention interventions targeting children aged 12 years or under and/or their parents or caregivers. Sixty-three records, describing 54 discrete studies were included; 32 applied a BCT taxonomy prospectively (i.e., to design interventions) and 23 retrospectively (i.e., to assess interventions), 1 study did both. There was substantial variation in the methods used to apply BCT taxonomies and to report BCT-related methods and results. There was a paucity of detail reported in how BCTs were selected in studies applying BCT taxonomies prospectively. Our review provides important insight into the application of BCT taxonomies in childhood obesity prevention and several ongoing challenges, pointing to the need for best practice reporting guidance.

Abstract Over the last century, the state of stress in the earth’s upper crust has undergone rapid changes because of human activities associated with fluid withdrawal and injection in subsurface formations. The stress dependency of multiphase flow mechanisms in earth materials is a substantial challenge to understand, quantify, and model for many applications in groundwater hydrology, applied geophysics, CO2 subsurface storage, and the wider geoenergy field (e.g., geothermal energy, hydrogen storage, hydrocarbon recovery). Here, we conduct core-scale experiments using N2/water phases to study primary drainage followed by spontaneous imbibition in a carbonate specimen under increasing isotropic effective stress and isothermal conditions. Using X-ray computed micro-tomography images of the unconfined specimen, we introduce a novel coupling approach to reconstruct pore-deformation and simulate multiphase flow inside the deformed pore-space followed by a semi-analytical calculation of spontaneous imbibition. We show that the irreducible water saturation increases while the normalized volume of spontaneously imbibed water into the specimen decreases (46–25%) in response to an increase in effective stress (0–30 MPa), leading to higher residual gas saturations. Furthermore, the imbibition rate decreases with effective stress, which is also predicted by a numerical model, due to a decrease in water relative permeability as the pore-space becomes more confined and tortuous. This fundamental study provides new insights into the physics of multiphase fluid transport, CO2 storage capacity, and recovery of subsurface resources incorporating the impact of poromechanics.

This study aimed to quantify, and examine grade level (Grade Kindergarten-2 vs. 3–6) and sex differences in the daily minutes of moderate-to-vigorous physical activity (MVPA) of primary school children, and the proportion of children meeting MVPA recommendations, across the school day and in break times. Consenting children in Kindergarten to Grade 6 from 12 Catholic primary schools within the Hunter region of New South Wales, Australia (February-April 2017) wore accelerometers during school hours (approx. 9am-3 pm) for five school days. Differences in student physical activity by Grade (Kindergarten-2; Grade 3–6) and sex were analysed using regression mixed modelling for the whole school day, during class time and break time. Valid data was available for 1862 students. Mean (SD) minutes of MVPA were consistently higher for Grade K-2 compared to Grade 3–6 students respectively, 37.02 (12.4) and 32.6 (12.2) across the school day; 20.4 (8.4) and 15.3 (7.6) minutes within breaks. Over the whole school day 69.7% of Grade K-2 and 54.1% of Grade 3–6 met the recommended 30 min of MVPA. Boys had higher MVPA than girls and a higher proportion of boys met MVPA recommendations than girls with 68.9% and 52.4% over whole school day and 6.43% and 0.98% respectively during break times. A large percentage of Australian children are not meeting physical activity guidelines whilst at school, with declining levels of physical activity from Grade K-2 to Grade 3–6 especially evident in girls.

Abstract Background Despite existing best practice care recommendations for addressing tobacco smoking, alcohol consumption and weight management in preconception and antenatal care, such recommendations are often not implemented into routine practice. Effective strategies that target known barriers to implementation are key to reducing this evidence to practice gap. The aim of this review is to synthesise the evidence on the effectiveness of implementation strategies in improving the provision of preconception and antenatal care for these modifiable risk factors. Methods Randomised and non-randomised study designs will be eligible for inclusion if they have a parallel control group. We will include studies that either compare an implementation strategy to usual practice or compare two or more strategies. Participants may include any health service providing preconception or antenatal care to women and/or the health professionals working within such a service. The primary outcome will be any measure of the effectiveness of implementation strategies to improve preconception and/or antenatal care for tobacco smoking, alcohol consumption and/or weight management (including care to improve nutrition and/or physical activity). Secondary outcomes will include the effect of the implementation strategy on women’s modifiable risk factors, estimates of absolute costs or cost-effectiveness and any reported unintentional consequences. Eligible studies will be identified via searching Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Maternity and Infant Care, CINAHL, ProQuest Dissertations and Theses and other sources (e.g. contacting experts in the field). Study selection, data extraction and risk of bias will be assessed independently by two review authors and differences resolved by a third reviewer. If data permits, we will conduct fixed-effects or random-effects meta-analysis where appropriate. If studies do not report the same outcome or there is significant heterogeneity, results will be summarised narratively. Discussion This review will identify which implementation strategies are effective in improving the routine provision of preconception and antenatal care for tobacco smoking, alcohol consumption and weight management. Such a review will be of interest to service providers, policy makers and implementation researchers seeking to improve women’s modifiable risk factors in preconception and antenatal care settings. Systematic review registration PROSPERO CRD42019131691

During the COVID-19 pandemic, West Virginia developed an aggressive SARS-CoV-2 testing strategy which included utilizing pop-up mobile testing in locations anticipated to have near-term increases in SARS-CoV-2 infections. This study describes and compares two methods for predicting near-term SARS-CoV-2 incidence in West Virginia counties. The first method, Rt Only, is solely based on producing forecasts for each county using the daily instantaneous reproductive numbers, Rt. The second method, ML+Rt, is a machine learning approach that uses a Long Short-Term Memory network to predict the near-term number of cases for each county using epidemiological statistics such as Rt, county population information, and time series trends including information on major holidays, as well as leveraging statewide COVID-19 trends across counties and county population size. Both approaches used daily county-level SARS-CoV-2 incidence data provided by the West Virginia Department Health and Human Resources beginning April 2020. The methods are compared on the accuracy of near-term SARS-CoV-2 increases predictions by county over 17 weeks from January 1, 2021- April 30, 2021. Both methods performed well (correlation between forecasted number of cases and the actual number of cases week over week is 0.872 for the ML+Rt method and 0.867 for the Rt Only method) but differ in performance at various time points. Over the 17-week assessment period, the ML+Rt method outperforms the Rt Only method in identifying larger spikes. Results show that both methods perform adequately in both rural and non-rural predictions. Finally, a detailed discussion on practical issues regarding implementing forecasting models for public health action based on Rt is provided, and the potential for further development of machine learning methods that are enhanced by Rt.

Conventional testing and diagnostic methods for infections like SARS-CoV-2 have limitations for population health management and public policy. We hypothesize that daily changes in autonomic activity, measured through off-the-shelf technologies together with app-based cognitive assessments, may be used to forecast the onset of symptoms consistent with a viral illness. We describe our strategy using an AI model that can predict, with 82% accuracy (negative predictive value 97%, specificity 83%, sensitivity 79%, precision 34%), the likelihood of developing symptoms consistent with a viral infection three days before symptom onset. The model correctly predicts, almost all of the time (97%), individuals who will not develop viral-like illness symptoms in the next three days. Conversely, the model correctly predicts as positive 34% of the time, individuals who will develop viral-like illness symptoms in the next three days. This model uses a conservative framework, warning potentially pre-symptomatic individuals to socially isolate while minimizing warnings to individuals with a low likelihood of developing viral-like symptoms in the next three days. To our knowledge, this is the first study using wearables and apps with machine learning to predict the occurrence of viral illness-like symptoms. The demonstrated approach to forecasting the onset of viral illness-like symptoms offers a novel, digital decision-making tool for public health safety by potentially limiting viral transmission.

The aim of the current study was to examine the association between Australian primary school children’s objectively measured in-school-hours weekly physical activity (PA) and their health-related quality of life (HRQoL). A cross-sectional study of 1128 Grade 2 and 3 children, aged 7–9 years, from 62 primary schools was conducted in New South Wales, Australia between October 2017 and April 2018. Children’s PA was assessed via an accelerometer worn for five days during school hours. Their parents completed a telephone interview, answering demographic, child HRQoL and out-of-school-hours PA questions. Children’s in-school-hours PA was classified as total PA and moderate-to-vigorous PA (MVPA). HRQoL scores were aggregated and reported at the high construct level domains (Total Quality of Life (Total HRQoL), Physical and Psychosocial Health Summary Scores). Multiple linear mixed regression analyses accounting for clustering were conducted to evaluate the association between children’s in-school-hours weekly PA and their HRQoL. After adjusting for potential confounders, significant positive associations were found between children’s in-school-hours weekly total PA and Total HRQoL (0.62 units, 95% CI: 0.29; 0.94, p < 0.001), Physical (0.71 units, 95% CI: 0.38; 1.04, p ≤ 0.001) and Psychosocial (0.58 units, 95% CI: 0.19; 0.97, p = 0.004) scores, with a stronger association observed between average weekly MVPA than average weekly total PA. There were also positive associations between PA and HRQoL for each sex when analysed separately. Our findings demonstrate a positive association between children’s objectively-measured in-school-hours PA and parent-reported child HRQoL, strengthening evidence supporting the continued implementation of school-based PA programs for broader health outcomes.

Clinical practice guidelines direct mental health services to provide preventive care to address client chronic disease risk behaviours, however, this care is not routinely provided. The aim of this systematic review was to synthesise evidence regarding the effectiveness of interventions to increase provision of preventive care by mental health services; by care element (ask, assess, advice, assist, arrange) and risk behaviour (tobacco smoking, poor nutrition, harmful alcohol consumption, physical inactivity). Electronic bibliographic databases, Google Scholar, relevant journals, and included study reference lists were searched. Eligible studies were of any design with a comparison group that reported the effectiveness of an intervention to increase the provision of at least one element of preventive care for at least one risk behaviour in a mental health setting. Twenty studies were included, most commonly examining smoking (n = 20) and ‘ask’ (n = 12). Meta-analysis found interventions involving task shifting were effective in increasing smoking ‘advice’ (n = 2 RCTs; p = 0.009) and physical activity ‘advice’ (n = 2 RCTs; p = 0.002). Overall, meta-analysis and narrative synthesis indicated that effective intervention strategies (categorised according to the Effective Practice and Organisation of Care taxonomy) were: task shifting, educational meetings, health information systems, local consensus processes, authority and accountability, and reminders. The most consistent findings across studies were with regard to preventive care for smoking, while conflicting or limited evidence was found regarding other risk behaviours. While further rigorous research examining key risk behaviours is recommended, the findings may inform the selection of strategies for future interventions and service delivery initiatives.

Preventive care to address client chronic disease risks is not frequently provided in community mental health services. Offering clients an additional preventive care consultation has been shown to increase client receipt of such care. The ability of this approach to have a beneficial impact at the population level is however dependent on its level of acceptability and uptake among clients. No studies have previously reported these outcomes when the additional consultation is universally offered to all clients of a community mental health service. To address this evidence gap, this descriptive study was undertaken to determine community mental health clients’ (1) reported acceptability, in principle, of such a model of care, (2) of those who were offered the additional consultation, the level of uptake, and (3) clinical and socio-demographic characteristics associated with uptake. Participants were clients of one community mental health service in Australia. Data were collected in 2017 by telephone interviews and study records. Data from three distinct participant sub-groups are reported. In response to a hypothetical question, 79.3% of participants (n = 157) agreed that an offer of an additional preventive care consultation would be acceptable (Aim 1). Of the participants who were offered such a consultation (n = 264), 37.8% took up the offer (Aim 2); and no clinical or sociodemographic characteristics were significantly associated with uptake (Aim 3). Findings support the feasibility of this model of care. However, further research is needed to identify barriers to uptake, and effective strategies to enhance consultation uptake.Trial registration: ACTRN12616001519448.

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.

Introduction Low back pain is one of the most common and burdensome chronic conditions worldwide. Lifestyle factors, such as excess weight, physical inactivity, poor diet and smoking, are linked to low back pain chronicity and disability. There are few high-quality randomised controlled trials that investigate the effects of targeting lifestyle risk factors in people with chronic low back pain.Methods and analysis The aim of this study is to determine the effectiveness of a Healthy Lifestyle Program (HeLP) for low back pain targeting weight, physical activity, diet and smoking to reduce disability in patients with chronic low back pain compared with usual care. This is a randomised controlled trial, with participants stratified by body mass index, allocated 1:1 to the HeLP intervention or usual physiotherapy care. HeLP involves three main components: (1) clinical consultations with a physiotherapist and dietitian; (2) educational resources; and (3) telephone-based health coaching support for lifestyle risk factors. The primary outcome is disability (Roland Morris Disability Questionnaire) at 26 weeks. Secondary outcomes include pain intensity, weight, quality of life and smoking status. Data will be collected at baseline, and at weeks 6, 12, 26 and 52. Patients with chronic low back pain who have at least one health risk factor (are overweight or obese, are smokers and have inadequate physical activity or fruit and vegetable consumption) will be recruited from primary or secondary care, or the community. Primary outcome data will be analysed by intention to treat using linear mixed-effects regression models. We will conduct three supplementary analyses: causal mediation analysis, complier average causal effects analysis and economic analysis.Ethics and dissemination This study was approved by the Hunter New England Research Ethics Committee (Approval No 17/02/15/4.05), and the University of Newcastle Human Research Ethics Committee (Ref No H-2017-0222). Outcomes of this trial and supplementary analyses will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration number ACTRN12617001288314.

Bee populations are currently undergoing severe global declines driven by the interactive effects of a number of factors. Ongoing urbanisation has the potential to exacerbate bee declines, unless steps are taken to ensure appropriate floral resources are available. Sown wildflower strips are one way in which floral resources can be provided to urban bees. However, the use of these strips by pollinators in urban environments remains little studied. Here, we employ pollen metabarcoding of the rbcL gene to compare the foraging patterns of different bee species observed using urban sown wildflower strips in July 2016, with a goal of identifying which plant species are most important for bees. We also demonstrate the use of a non-destructive method of pollen collection. Bees were found to forage on a wide variety of plant genera and families, including a diverse range of plants from outside the wildflower plots, suggesting that foragers visiting sown wildflower strips also utilize other urban habitats. Particular plants within the wildflower strips dominated metabarcoding data, particularly Papaver rhoeas and Phacelia tanacetifolia. Overall, we demonstrate that pollinators observed in sown wildflower strips use certain sown foodplants as part of a larger urban matrix.

Background Osteoarthritis and spinal pain are common and burdensome conditions; however, the majority of patients with these conditions do not receive care that is consistent with clinical practice guidelines. Telehealth models of care have the potential to improve care for osteoarthritis and spinal pain patients. The aim of this review was to assess the effectiveness of verbal real-time telehealth interventions, including telephone-based and videoconferencing interventions to reduce pain intensity and disability in patients with osteoarthritis of the knee or hip and spinal pain (back or neck pain). Methods We searched seven electronic databases from inception to May 2018. Randomised controlled trials (RCTs), cluster-RCTs, and non-randomised controlled trials were included. Two review authors independently extracted data for each included study. Primary outcomes were pain intensity and disability. We conducted primary meta-analyses combining all conditions with similar interventions and comparators. Standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated using random effects models. We used the Cochrane Risk of Bias tool to assess risk of bias, and GRADE to evaluate the quality of evidence. Results We included 23 studies with 56 trial arms and 4,994 participants. All studies utilised telephone-based interventions. Only two studies used a telephone only approach and the remainder included educational materials and/or face-to-face components. We found no studies utilising videoconferencing. Meta-analysis showed telephone-based interventions (with educational materials) for osteoarthritis and spinal pain improved pain intensity (n = 5 trials, n = 1,357 participants, SMD −0.27, 95% CI [−0.53, −0.01], Tau2 = 0.06, I2 = 74%; moderate-quality evidence) and disability (n = 7 trials, n = 1,537 participants, SMD −0.21, 95% CI [−0.40, −0.02], Tau2 = 0.03, I2 = 56%; moderate-quality evidence) compared to usual care. Meta-analyses found telephone with face-to-face interventions does not improve pain and disability compared to usual care or face-to-face care alone. Discussion We are moderately confident that telephone-based interventions reduce pain intensity and disability in patients with osteoarthritis and spinal pain compared to usual care, but telephone plus face-to-face interventions are no more effective than usual care or face-to-face interventions alone.

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases.

In early 1976, the novel A/New Jersey/76 (Hsw1N1) influenza virus caused severe respiratory illness in 13 soldiers with 1 death at Fort Dix, New Jersey. Since A/New Jersey was similar to the 1918–1919 pandemic virus, rapid outbreak assessment and enhanced surveillance were initiated. A/New Jersey virus was detected only from January 19 to February 9 and did not spread beyond Fort Dix. A/Victoria/75 (H3N2) spread simultaneously, also caused illness, and persisted until March. Up to 230 soldiers were infected with the A/New Jersey virus. Rapid recognition of A/New Jersey, swift outbreak assessment, and enhanced surveillance resulted from excellent collaboration between Fort Dix, New Jersey Department of Health, Walter Reed Army Institute of Research, and Center for Disease Control personnel. Despite efforts to define the events at Fort Dix, many questions remain unanswered, including the following: Where did A/New Jersey come from? Why did transmission stop?

Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.

Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML). Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Förster resonance energy transfer (TR-FRET) -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1. This assay was used in a high throughput screen (HTS) of two small molecule libraries totaling 444,743 compounds. 708 confirmed hits were counter-screened to eliminate off-target inhibitors and reanalyzed to prioritize compounds with IC50 values below 10 μM. The CML cell line K562 was then used to identify five compounds that decrease MAPK1/3 phosphorylation, which we determined to be an indicator of RIN1-dependent ABL signaling. One of these compounds is a thiadiazole, and the other four are structurally related acyl piperidine amides. Notably, these five compounds lower cellular BCR-ABL1 kinase activity by blocking a positive regulatory interaction rather than directly inhibiting ABL catalytic function.