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Abstract Background Transgender and gender expansive (TGE) youth often seek a variety of gender-affirming healthcare services, including pubertal suppression and hormone therapy requiring that TGE youth and their parents participate in informed consent and decision making. While youth must demonstrate the ability to understand and appreciate treatment options, risks, benefits, and alternatives as well as make and express a treatment choice, standardized approaches to assess the capacity of TGE youth to consent or assent in clinical practice are not routinely used. This scoping review identified the currently available data regarding adolescent capacity to consent to gender-affirming medical treatments. Methods Articles relevant to assessing adolescent capacity for clinical decision-making were identified using OVID Medline, Web of Science, and PubMed. Articles were reviewed and thematically analyzed. Results Eight relevant articles were identified using three tools for measuring adolescent clinical decision-making capacity: Measure of Understanding, Measure of Competence, and MacArthur Competence Assessment Tool (MacCAT). These studies explored hypothetical treatment decisions, mental health treatment decisions, HIV treatment decisions, genetic testing decisions, and gender-affirming medical decisions. Only one study specifically examines the capacity of TGE youth to consent to medical treatments. Age was correlated with capacity in most, but not all studies. Other studies found cognitive measures (IQ, literacy, numeracy) may impact important aspects of capacity (understanding and reasoning). Conclusions For clinicians caring for TGE youth, tools such as the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) may prove useful, in conjunction with consideration of youth developmental abilities and utilization of shared decision-making practices. A standardized, collaborative approach to assessing TGE youth capacity would benefit TGE youth and their parents, and allow clinicians to more easily resolve ethical concerns.

Abstract Background Gaps in discharge planning are experienced by 41% of hospital patients in Australia. There is an established body of knowledge regarding the features of the discharge process that need to be improved to avoid subsequent hospital readmission and enhance the discharge experience. However, many of these studies have focused solely on factors related to unplanned hospital readmissions and there has been limited success in operationalising improvements to the discharge process. The aim of this study was to explore and describe the factors that influence the decision to discharge adult medical patients from hospital, from patient, carer and staff perspectives. Methods A qualitative descriptive study was conducted in one acute medical ward in Melbourne, Australia. The study data were collected by observations of clinical practice and semi-structured interviews with patients, carers and staff. Participants were: i) English-speaking adults identified for discharge home, ii) patient carers, and iii) staff involved in the discharge process. Observation data were analysed using content analysis and interviews data were analysed using thematic analysis. Results Twenty-one discharges were observed, and 65 participants were interviewed: 21 patients, two carers, and 42 staff. Most patients (76%) were identified as being ready for discharge during morning medical rounds, and 90% of discharge decisions were made collaboratively by the medical team and the patient. Carers were observed to be notified in 15 discharges by the patient (n = 8), doctors (n = 4), or nursing staff (n = 3). Five themes were constructed from thematic analysis of interviews: Readiness for Home, Fragmented Collaboration, Health Literacy, Unrealistic Expectations, and Care beyond Discharge. A collaborative team and supportive carers were considered to enhance risk assessment and discharge planning, however fragmented communication between clinicians, and between clinicians and patients/carers was a barrier to discharge decision-making. Conclusions Our study highlights the need for a more coordinated approach to discharge decision-making that optimises communication with patients and carers and multidisciplinary workflows and reduces fragmentation. The importance of patient-centred care and a personalised approach to care are well established. However, there is a need to design systems to customise the entirety of the patient journey, including the approach to discharge decision making.

Abstract Background Suicide is among the leading causes of death for adults with schizophrenia spectrum disorders (SSDs), and there is a paucity of evidence-based suicide prevention-focused interventions tailored for this vulnerable population. Cognitive-Behavioral Suicide Prevention for psychosis (CBSPp) is a promising intervention developed in the UK that required modifications for delivery in community mental health (CMH) settings in the United States of American. This pilot trial evaluates the feasibility, acceptability, and preliminary effectiveness of our modified CBSPp intervention in comparison to services as usual (SAU) within a CMH setting in a Midwestern state of the USA. Methods This is a single-site randomized pilot trial with a planned enrollment of 60 adults meeting criteria for both SSD and SI/A. Eligible participants will be randomized 1:1 to either 10 sessions of CBSPp or SAU. Clinical and cognitive assessments will be conducted within a 4-waive design at baseline (prior to randomization and treatment) and approximately 1 month (mid-treatment), 3 months (post-treatment), and 5 months (follow-up) after baseline assessment. Qualitative interviews will also be conducted at post-treatment. The primary objective is to determine whether CBSPp is feasible and acceptable, involving examinations of recruitment rate, treatment engagement and adherence, retention and completion rates, and experiences in the CBSPp treatment and overall study. The secondary objective is to preliminarily evaluate whether modified CBSPp is associated with reductions in clinical (suicide ideation, suicide attempt, symptoms of psychosis, depression, and emergency/hospital service, hopelessness, defeat, and entrapment) and cognitive (information processing biases, appraisals, and schemas) outcomes in comparison to SAU from baseline to post-treatment assessment. Discussion This randomized pilot trial will provide clinically relevant information about whether CBSPp can improve SI/A, depression, and psychosis among adults with SSDs. Testing this modified cognitive-behavioral suicide prevention-focused intervention has the potential for a large public health impact by increasing the intervention’s utility and usability in CMH where many individuals with SSDs receive care, and ultimately working towards reductions in premature suicide death. Trial registration ClinicalTrials.gov NCT#05345184. Registered on April 12, 2022.

Abstract Soils are a principal global reservoir of mercury (Hg), a neurotoxic pollutant that is accumulating through anthropogenic emissions to the atmosphere and subsequent deposition to terrestrial ecosystems. The fate of Hg in global soils remains uncertain, however, particularly to what degree Hg is re-emitted back to the atmosphere as gaseous elemental mercury (GEM). Here we use fallout radionuclide (FRN) chronometry to directly measure Hg accumulation rates in soils. By comparing these rates with measured atmospheric fluxes in a mass balance approach, we show that representative Arctic, boreal, temperate, and tropical soils are quantitatively efficient at retaining anthropogenic Hg. Potential for significant GEM re-emission appears limited to a minority of coniferous soils, calling into question global models that assume strong re-emission of legacy Hg from soils. FRN chronometry poses a powerful tool to reconstruct terrestrial Hg accumulation across larger spatial scales than previously possible, while offering insights into the susceptibility of Hg mobilization from different soil environments.

Abstract Seaweed consumption has gained popularity due to its nutritional value and potential health benefits. However, concerns regarding the bioaccumulation of several trace elements highlight the need for comprehensive studies on exposure associated with seaweed consumption. To address this gap in knowledge, we carried out a feeding intervention study of three common edible seaweeds (Nori, Kombu, and Wakame) in 11 volunteers, aiming to elucidate the extent of both beneficial and harmful trace element exposure through seaweed consumption in humans. Concentrations of total arsenic, cobalt, copper, cadmium, iodine, molybdenum, selenium, and zinc were measured in urine samples before and following seaweed consumption. Elements concentrations were also measured in the seaweeds provided for the study. Descriptive analysis for each element were conducted and we used quantile g-computation approach to assess the association between the 8-element mixture and seaweed consumption. Differences in urine element concentrations and seaweed consumption were analyzed using generalized estimating equations (GEE). Urinary concentrations of iodine and total arsenic increased after seaweed consumption. When we analyze the 8-element mixture, the largest weight was observed for iodine after Kombu consumption while for total arsenic was observed after Wakame consumption. Similar results were observed when we compared the mean differences between the elements before and after seaweed consumption through the GEE. Seaweed consumption relates with increased urinary iodine and total arsenic concentrations, particularly after Kombu and Wakame consumption.

Exercise for people with Prader-Willi syndrome (PWS) is important for their health and wellbeing and can provide opportunities for community participation. However, they may find it difficult to participate in some contexts, such as community gyms because social and environmental barriers in these settings may compound difficulties caused by physical impairments or intellectual disability. This study aims to observe and understand the actions and interactions of people with PWS when they exercise in community gyms. A focussed ethnographic study will be conducted. Field notes will be taken in community gyms where people with PWS are participating in a structured exercise program for six months as part of a randomised control trial called PRESTO. Up to ten participants will be observed, with at least three observations planned per participation during the program. Gym sessions observed will be approximately 1 hour long. Within the framework of interpretive description, reflective thematic analysis will be used to interpret observational data. Our findings will inform how best to support people with PWS to exercise at a community gym. Trial Registration Number: ACTRN12620000416998; Australian and New Zealand Clinical Trial Registry.

Background: As physical function and physical activity are often compromised among children and adolescents undergoing acute cancer treatment, psychometrically robust and feasible assessment tools are needed. The aim of this study is to evaluate the construct validity, responsiveness and feasibility of one physical activity assessment tool (Fitbit Inspire); and six physical function assessment tools (Movement ABC-2, Timed Up and Go, 30-s Chair Stand, Timed Rise from the Floor, Timed Up and Down Stairs, 6-min Walk Test) for children undergoing acute cancer treatment. Methods: A prospectively-registered, mixed methods, single-group study evaluated measurement properties against a priori hypothesis using Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) framework. Feasibility was assessed quantitively (a priori thresholds), and qualitatively (semi-structured interviews, focus-groups). Results: Twenty children/adolescents (median age 13 ​± ​5 years, various cancer diagnoses), 20 parents and 16 clinicians participated. Fitbit was feasible to assess daily steps only, had evidence of construct validity, tendency to overestimate step count and adequate evidence of responsiveness (compared to Actigraph). The 30-s Chair stand, 6-min Walk Test and Timed Up and Go were feasible and showed evidence of construct validity and responsiveness. To maximise feasibility, consideration of timing and intent of assessment are crucial. Conclusion: Fitbit has limitations as a physical activity assessment tool. The 30-s Chair Stand, 6-min Walk Test and Timed Up and Go were feasible to use and showed favourable measurement properties to assess physical function.

Introduction: Obesity is a preventable chronic condition and a risk factor for poor health and early mortality. Weight stigma and weight-neutral medicine are popular topics in social media that are often at odds with current medical guidelines on obesity treatment and prevention. This conflict may erode the public’s trust in science, impede research progress on preventing obesity in marginalized groups, and uphold the ongoing and historical lack of diversity among nutrition trainees. Methods: The authors conducted a series of student-led dialogue sessions with nutrition graduate students in Boston, Massachusetts, from March to May 2023 to understand perceptions of obesity research, health equity, and racism and discrimination. This article summarizes the lessons learned and provides pedagogical recommendations for jointly addressing obesity at the population level and the recruitment, training, and retention of diverse scholars, clinicians, and public health practitioners. Results: Dialogue sessions revealed that students perceive a disproportionate focus on the harms of obesity as a chronic disease, highlighting that inadequate attention is given to weight stigma and discrimination. Some participants believed that weight-based discrimination is equally detrimental to individual health and wellbeing as having obesity. Discussions also emphasized the need to pinpoint the multidimensional and cultural manifestations of weight stigma, which necessitates collaboration across social sectors and academic disciplines. Students recognized the urgent need to apply an equity lens to obesity research and teaching but felt limited in their access to experts within nutrition science who specialize in racism, discrimination, eating disorders, and weight stigma. Conclusions: This study identified concrete opportunities for urgently needed new training and research in population-level obesity prevention, emphasizing antiracism, harm reduction, and elimination of stigma and bias across multiple levels of science and society. Overall, the decision to use the BMI within pedagogy and training must be explicitly stated—research, population surveillance, decision-making, or treatment pedagogy and training—while acknowledging its strengths and limitations across diverse settings. Finally, the social determinants of obesity should incorporate not only weight stigma but also racism and multiple forms of discrimination.

Abstract Background Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. Methods Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at “high genetic risk” were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. Results A total of 3818 children aged 2–16 years were recruited, with 14.2% (n = 542) having a “high genetic risk.” Of children with “high genetic risk” and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a “high genetic risk.” In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. Conclusions Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used class of medications worldwide. It is estimated that more than 20 million people take NSAIDs daily. We examined the underreported use of NSAIDs on a standardized office intake assessment questionnaire of patient reported medications. A questionnaire was administered to patients following written and verbal confirmed report of current medications to nursing staff. One hundred consecutive patient intake assessments were evaluated from the patient intake sheets for a busy private gastroenterology specialty practice. After patients listed their current medications, they were given a survey and asked to acknowledge any use of 30 non-prescription formulations that contained NSAIDs. Patients filled these surveys while waiting for the health care provider who then reviewed the response accuracy with the patient during the visit. Changes in the patient‘s initial and subsequently corroborated use or non-use of NSAIDs were recorded and tabulated. The educational level of all participants was also assessed. Of the 100 surveys completed, 6% of patients had not completed high school, 19% had completed high school, 8% had started but not finished college, 54% had completed college, 2% had started but not finished graduate school, and 11% had completed graduate school. The educational level of the patients did not correlate with underreporting of NSAID usage. On the survey, 18% of patients noted use of an NSAID listed that had not been reported verbally to nursing staff; 8% of those patients reported daily use, 15% weekly use and 76% reported use within the last month. Patients were then asked in the questionnaire as to the reason for not reporting medication intake to nurse; 14% stated they were never asked about the specific medication, 22% did not think the medications were important enough to list, 34% bought the medication with prescriptions, and 30% noted their reason as their doctor did not prescribe the medication to them. Using a prospective questionnaire in a private practice gastrointestinal office, these data show that patients underreport use of non-prescription NSAIDs. Based on the data, it is clear that this underreporting can have a detrimental effect on procedure related as well as long-term patient care. Future studies would be needed to examine the incidence of side effects due to underreporting of NSAIDs.

Abstract Background Delayed access to outpatient care may negatively impact on health outcomes. We aimed to evaluate implementation of the Specific Timely Appointments for Triage (STAT) model of access in an epilepsy clinic to reduce a long waitlist and waiting time. Methods This study is an intervention study using pre-post comparison and an interrupted time series analysis to measure the effect of implementation of the STAT model to an epilepsy clinic. Data were collected over 28 months to observe the number of patients on the waitlist and the waiting time over three time periods: 12 months prior to implementation of STAT, ten months during implementation and six months post-intervention. STAT combines one-off backlog reduction with responsive scheduling that protects time for new appointments based on historical data. The primary outcomes were the number of patients on the waitlist and the waiting time across the three time periods. Secondary outcomes evaluated pre- and post-intervention changes in number of appointments offered weekly, non-arrival and discharge rates. Results A total of 938 patients were offered a first appointment over the study period. The long waitlist was almost eliminated, reducing from 616 during the pre-intervention period to 11 post-intervention (p = 0.002), but the hypothesis that waiting time would decrease was not supported. The interrupted time series analysis indicated a temporary increase in waiting time during the implementation period but no significant change in slope or level in the post- compared to the pre-intervention period. Direct comparison of the cohort of patients seen in the pre- and post-intervention periods suggested an increase in median waiting time following the intervention (34 [IQR 25–86] to 46 [IQR 36–61] days (p = 0.001)), but the interquartile range reduced indicating less variability in days waited and more timely access for the longest waiters. Conclusions The STAT model was implemented in a specialist epilepsy outpatient clinic and reduced a large waitlist. Reductions in the waitlist were achieved with little or no increase in waiting time. The STAT model provides a framework for an alternative way to operate outpatient clinics that can help to ensure that all people referred are offered an appointment in a timely manner.

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized ‘codes’ that are read by specialized regions (reader domains) in chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP: histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher-order factors. Here, we show that the [BPTF PHD finger and bromodomain: histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the ‘histone code’ concept and interrogate it at the nucleosome level.

Introduction: Workplace injuries are a serious issue for the health and social care industry, with the sector accounting for 20 % of all serious claims reported. The aim of this systematic review was to determine whether patient handling training interventions that included instruction on patient transfer techniques are effective in preventing musculoskeletal injuries in healthcare workers. Methods: Electronic databases MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Health and Safety Science Abstracts (ProQuest) were searched for controlled trials from January 1996–August 2022. Risk of bias was evaluated using the PEDro scale and overall certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluation for each meta-analysis. Results: A total of nine studies (3903 participants) were included. There is moderate certainty evidence that could not conclude whether patient handling training affects the 12-month incidence of lower back pain (OR = 0.83, 95 % CI [0.59, 1.16]). There is low certainty evidence that patient handing training does not prevent lower back pain in health professionals without pre-existing pain (MD = −0.06, 95 % CI [-0.63, 0.52]) but may reduce lower back pain in those with pre-existing pain (MD = −2.92, 95 % CI [-5.44, −0.41]). The results also suggest that there may be a positive effect of training incorporating risk assessment on musculoskeletal injury rates; however the evidence is of very low certainty. There is low certainty evidence from a single study that training may have a short-term effect on sickness absences.) Conclusions: There is a lack of evidence to support patient handling training when delivered to all healthcare staff. Training in its current form may be an ineffective strategy for reducing musculoskeletal injuries and pain. High quality disinvestment studies or trials incorporating risk assessment strategies are warranted. Practical Applications: This review suggests health service managers question the effectiveness of current patient handling training practices and consider evaluating current practices before allocating resources to meet employee risk reduction obligations.

Abstract Ever gazed at the stars and wondered if we’re alone? Scientists have been on a quest to find life beyond Earth, but no aliens yet. It’s tough because space is huge, and potential life is incredibly far away, making it difficult to detect their signals. Despite this, our ability to search is improving. We’ve found many planets around other stars, hinting at more places where life could be. But life, especially intelligent life, seems to be a rare occurrence, which makes our existence on Earth quite extraordinary. Recording our search for extraterrestrial life is crucial. It’s a way for future generations or even other civilizations to understand our era and our views of the cosmos. It also makes us reflect on our own behavior on Earth, hinting that insights from the search might help us coexist more harmoniously.

Introduction Key to improving outcomes for patients with multimorbidity is increasing mobility through prescription of a physical activity programme, but this can be difficult to achieve in acute hospital settings. One approach that would assist physiotherapists to increase levels of physical activity is delegation of rehabilitation to allied health assistants. We aim to conduct a randomised controlled trial to determine the feasibility of an allied health assistant providing daily inpatient mobility rehabilitation for patients with multimorbidity.Methods and analysis Using a parallel group randomised controlled design, participants will be allocated to allied health assistant mobility rehabilitation or physiotherapist mobility rehabilitation. Adult inpatients (n=60) in an acute hospital with a diagnosis of multimorbidity who walked independently preadmission will be included. The experimental group will receive routine mobility rehabilitation, including daily mobilisation, from an allied health assistant under the supervision of a physiotherapist. The comparison group will receive routine rehabilitation from a physiotherapist. Feasibility will be determined using the following areas of focus in Bowen’s feasibility framework: Acceptability (patient satisfaction); demand (proportion of patients who participate); implementation (time allied health assistant/physiotherapist spends with participant, occasions of service); and practicality (cost, adverse events). Staff involved in the implementation of allied health assistant rehabilitation will be interviewed to explore their perspectives on feasibility. Secondary outcomes include: Physical activity (daily time spent walking); daily mobilisation (Y/N); discharge destination; hospital readmission; falls; functional activity (Modified Iowa Level of Assistance Scale); and length of stay. Descriptive statistics will be used to describe feasibility. Secondary outcomes will be compared between groups using Poisson or negative binomial regression, Cox proportional hazards regression, survival analysis, linear regression or logistic regression.Ethics and dissemination Ethics approval was obtained from Peninsula Health (HREC/97 431/PH-2023). Findings will be disseminated in peer-reviewed journals and conference presentations.Trial registration number Australian and New Zealand Clinical Trial Registry ACTRN12623000584639p.

Purpose: Delays in outpatient specialist neurologist care for people with epilepsy are common despite recommendations for prompt access. There is evidence to suggest that there are interventions that can minimise waitlists and waiting time. However, little is known about whether such interventions can result in sustained improvements in waiting. The aim of this study was to determine the extent to which an intervention to reduce waiting in an epilepsy specialist outpatient clinic demonstrated sustained outcomes two years after the intervention was implemented. Methods: This observational study analysed routinely collected epilepsy clinic data over three study periods: pre-intervention, post-intervention and at two-year follow-up. The intervention, Specific Timely Assessment and Triage (STAT), combined a short-term backlog reduction strategy and creation of protected appointments for new referrals based on analysis of demand. After the initial intervention, there was no further active intervention in the following two years. The primary outcome was waiting measured by 1.) waiting time for access to a clinic appointment, defined as the number of days between referral and first appointment for all patients referred to the epilepsy clinic during the three study periods; and 2.) a snapshot of the number of patients on the waitlist at two time points for each of the three study periods. Results: Two years after implementing the STAT model in an epilepsy clinic, median waiting time from post-intervention to two-year follow-up was stable (52–51 days) and the interquartile range of days waited reduced from 37 to 77 days post-intervention to 45–57 days at two-year follow-up, with a reduction in the most lengthy wait times observed. After a dramatic reduction of the total number of patients on the waitlist immediately following the intervention, a small rise was seen at two years (n = 69) which remained well below the pre-intervention level (n = 582). Conclusion: The STAT model is a promising intervention for reducing waiting in an epilepsy clinic. While there was a small increase in the waitlist after two years, the median waiting time was sustained.

Abstract In the first part of this series, we delve into the foundational aspects of “Message in a Bottle (MIAB)” (henceforth referred to as MIAB). This study builds upon the legacy of the Voyager Golden Records, launched aboard Voyager 1 and 2 in 1977, which aimed to communicate with intelligent species beyond our world. These records not only offer a snapshot of Earth and human civilization but also represent our desire to establish contact with advanced alien civilizations. Given the absence of mutually understood signs, symbols, and semiotic conventions, MIAB, like its predecessor, uses scientific methods to design an innovative means of communication that encapsulates the story of humanity. Our goal is to share our collective knowledge, emotions, innovations, and aspirations in a way that provides a universal, yet contextually relevant, understanding of human society, the evolution of life on Earth, and our hopes and concerns for the future. Through this time and space traveling capsule, we also strive to inspire and unify current and future generations to celebrate and safeguard our shared human experience.

Abstract Background The Risk Assessment for moving Individuals SafEly (RAISE) program is a hospital-based manual handling nursing training program. RAISE involves upskilling on continual risk assessment during patient-assisted movements. RAISE aims to optimise staff and patient safety while providing the patient with movement and rehabilitation opportunities. Implementation of RAISE in the hospital setting has been established. The aim of this study was to explore the feasibility of implementing RAISE in the long-term care setting. Methods We examined three feasibility domains: acceptability, practicality, and limited efficacy (observed nursing behaviour change which has the potential to reduce nursing injuries), using a prospective pilot pre-post design in the long-term care setting. Staff completed a 4-hour training session on RAISE delivered by two physiotherapists, followed by 8 h of supported behaviour change in the workplace. Staff acceptability and practicality of incorporating risk assessment strategies into manual handling approaches were explored through pre- and post-training staff surveys and a semi-structured interview. Resident acceptability of manual handling practices was explored via survey data collected after the RAISE training. Pre to post-training changes in staff knowledge and behaviour were examined through the pre- and post-training staff survey, and observation of staff assisting resident movement. Results Two enrolled nurses and five residents participated. Staff reported the RAISE program was acceptable and practical to implement in the long-term care setting. There were no adverse events or safety concerns. Staff reported the RAISE program provided guidance and enhanced staff empowerment to make decisions during assisted resident movement. There were 26 observed resident-staff manual handling interactions recorded, with 13 pre-training and 13 post-training. Post-training, RAISE skills had improved and were completed 100% of the time, except for completing a physical risk assessment which improved from 46 to 85%, demonstrating limited efficacy. Residents reported it’s important for staff to be trained on how to assist them to mobilise and they found the concept of the RAISE program acceptable. Conclusions This pilot study supports the feasibility of long-term care facilities participating in future studies testing the effectiveness and cost-effectiveness of the Risk Assessment for moving Individuals SafEly (RAISE) patient and resident manual handling program.

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained

Retention of care support workers in residential aged care facilities and home-based, domiciliary aged care is a global challenge, with rapid turnover, low job satisfaction, and poorly defined career pathways. A mixed-methods systematic review of the workforce literature was conducted to understand the factors that attract and retain care staff across the aged care workforce. The search yielded 49 studies. Three studies tested education and training interventions with the aim of boosting workforce retention and the remaining 46 studies explored opinions and experiences of care workers in 20 quantitative, four mixed-methods and 22 qualitative studies. A range of factors impacted retention of aged care staff. Two broad themes emerged from the analysis: individual and organisational factors facilitating retention. Individual factors related to personal satisfaction with the role, positive relationships with other staff, families, and residents, and a cooperative workplace culture. Organisational factors included opportunities for on-the-job training and career development, appropriate wages, policies to prevent workplace injuries, and job stability. Understaffing was often cited as a factor associated with turnover, together with heavy workloads, stress, and low job satisfaction. With global concerns about the safety and quality of aged care services, this study presents the data associated with best practice for retaining aged care workers.

Diploid and triploid Atlantic salmon show distinct physiological differences including heart, brain, and digestive system morphology, propensity for certain deformities, temperature tolerance as eggs and once hatched, and different nutritional requirements. Whilst several studies have looked in detail at the rate of embryogenesis in diploid salmon, no study has compared the rate of embryogenesis between ploidies from fertilisation to hatch. This study based its assessment on a seminal paper by Gorodilov (1996) and used the same techniques to compare the rate at which triploid and diploid embryos developed morphological characteristics. Whilst no significant difference was found, this study provides well-needed justification for the assumption that both ploidies develop at the same rate and gives scientific weight to studies which involve manipulation at these stages of development. Two factors that did differ, however, were the timing of hatch, and mortality. Triploids hatched more quickly than diploids and reached 50% hatch at a significantly earlier point. Triploids also suffered from a significantly higher rate of mortality.

Abstract Background DNA methylation has an important role in intergenerational inheritance. An increasing number of studies have reported evidence of germline inheritance of DNA methylation induced by nutritional signals in mammals. Vitamins and minerals as micronutrients contribute to growth performance in vertebrates, including Atlantic salmon (Salmo salar), and also have a role in epigenetics as environmental factors that alter DNA methylation status. It is important to understand whether micronutrients in the paternal diet can influence the offspring through alterations of DNA methylation signatures in male germ cells. Results Here, we show the effect of micronutrient supplementation on DNA methylation profiles in the male gonad through a whole life cycle feeding trial of Atlantic salmon fed three graded levels of micronutrient components. Our results strongly indicate that micronutrient supplementation affects the DNA methylation status of genes associated with cell signalling, synaptic signalling, and embryonic development. In particular, it substantially affects DNA methylation status in the promoter region of a glutamate receptor gene, glutamate receptor ionotropic, NMDA 3A-like (grin3a-like), when the fish are fed both medium and high doses of micronutrients. Furthermore, two transcription factors, histone deacetylase 2 (hdac2) and a zinc finger protein, bind to the hyper-methylated site in the grin3a-like promoter. An estimated function of hdac2 together with a zinc finger indicates that grin3a-like has a potential role in intergenerational epigenetic inheritance and the regulation of embryonic development affected by paternal diet. Conclusions The present study demonstrates alterations of gene expression patterns and DNA methylation signatures in the male gonad when Atlantic salmon are fed different levels of micronutrients. Alterations of gene expression patterns are of great interest because the gonads are supposed to have limited metabolic activities compared to other organs, whereas alterations of DNA methylation signatures are of great importance in the field of nutritional epigenetics because the signatures affected by nutrition could be transferred to the next generation. We provide extensive data resources for future work in the context of potential intergenerational inheritance through the male germline.

Abstract Background There is currently little evidence of planning for real-world implementation of physical activity interventions. We are undertaking the ComeBACK (Coaching and Exercise for Better Walking) study, a 3-arm hybrid Type 1 randomised controlled trial evaluating a health coaching intervention and a text messaging intervention. We used an implementation planning framework, the PRACTical planning for Implementation and Scale-up (PRACTIS), to guide the process evaluation for the trial. The aim of this paper is to describe the protocol for the process evaluation of the ComeBACK trial using the framework of the PRACTIS guide. Methods A mixed methods process evaluation protocol was developed informed by the Medical Research Council (MRC) guidance on process evaluations for complex interventions and the PRACTIS guide. Quantitative data, including participant questionnaires, health coach and administrative logbooks, and website and text message usage data, is being collected over the trial period. Semi-structured interviews and focus groups with trial participants, health coaches and health service stakeholders will explore expectations, factors influencing the delivery of the ComeBACK interventions and potential scalability within existing health services. These data will be mapped against the steps of the PRACTIS guide, with reporting at the level of the individual, provider, organisational and community/systems. Quantitative and qualitative data will elicit potential contextual barriers and facilitators to implementation and scale-up. Quantitative data will be reported descriptively, and qualitative data analysed thematically. Discussion This process evaluation integrates an evaluation of prospective implementation and scale-up. It is envisaged this will inform barriers and enablers to future delivery, implementation and scale-up of physical activity interventions. To our knowledge, this is the first paper to describe the application of PRACTIS to guide the process evaluation of physical activity interventions. Trial registration Australian and New Zealand Clinical Trials Registry ( ANZCTR ) Registration date: 10/12/2018.

Bovine herpesvirus 1 (BoHV-1), is associated with several clinical syndromes in cattle, among which bovine respiratory disease (BRD) is of particular significance. Despite the importance of the disease, there is a lack of information on the molecular response to infection via experimental challenge with BoHV-1. The objective of this study was to investigate the whole-blood transcriptome of dairy calves experimentally challenged with BoHV-1. A secondary objective was to compare the gene expression results between two separate BRD pathogens using data from a similar challenge study with BRSV. Holstein-Friesian calves (mean age (SD) = 149.2 (23.8) days; mean weight (SD) = 174.6 (21.3) kg) were either administered BoHV-1 inoculate (1 × 107/mL × 8.5 mL) (n = 12) or were mock challenged with sterile phosphate buffered saline (n = 6). Clinical signs were recorded daily from day (d) −1 to d 6 (post-challenge), and whole blood was collected in Tempus RNA tubes on d six post-challenge for RNA-sequencing. There were 488 differentially expressed (DE) genes (p < 0.05, False Discovery rate (FDR) < 0.10, fold change ≥2) between the two treatments. Enriched KEGG pathways (p < 0.05, FDR

The current methods used for producing triploid Atlantic salmon are generally reliable but not infallible, and each batch of triploids must be validated to ensure consumer trust and licensing compliance. Microsatellites have recently been shown to offer a cheaper and more convenient alternative to traditional flow cytometry for triploidy validation in a commercial setting. However, incubating eggs to at least the eyed stage for microsatellite validation poses challenges, such as reduced quality and performance of triploids produced from later eggs in the stripping season. To address these issues, we propose another option: extracting DNA from recently fertilised eggs for use in conjunction with microsatellite validation. To achieve this, we have developed an optimized protocol for HotSHOT extraction that can rapidly and cheaply extract DNA from Atlantic salmon eggs, which can then be used for triploidy validation through microsatellites. Our approach offers a simpler and more cost-effective way to validate triploidy, without the need for skilled dissection or expensive kits.

BackgroundAutologous stem cell transplant is a common procedure for people with haematological malignancies. While effective at improving survival, autologous stem cell transplant recipients may have a lengthy hospital admission and experience debilitating side-effects such as fatigue, pain and deconditioning that may prolong recovery. Prehabilitation comprising exercise and nutrition intervention before stem cell transplant aims to optimise physical capacity before the procedure to enhance functional recovery after transplant. However, few studies have evaluated prehabilitation in this setting. We aim to explore preliminary efficacy of improving physical capacity of prehabilitation for people undergoing autologous stem cell transplant.MethodsThe PIRATE study is a single-blinded, parallel two-armed pilot randomised trial of multidisciplinary prehabilitation delivered prior to autologous stem cell transplantation. Twenty-two patients with haematological malignancy waitlisted for transplant will be recruited from a tertiary haematology unit. The intervention will include up to 8 weeks of twice-weekly, supervised tailored exercise and fortnightly nutrition education delivered via phone, in the lead up to autologous stem cell transplant. Blinded assessments will be completed at week 13, approximately 4 weeks after transplant and health service measures collected at week 25 approximately 12 weeks after transplant. The primary outcome is to assess changes in physical capacity using the 6-minute walk test. Secondary measures are time to engraftment, C-reactive protein, physical activity (accelerometer), grip strength, health-related quality of life (EORTC QLQ-C30 and HDC29 supplement), self-efficacy and recording of adverse events. Health service data including hospital length of stay, hospital readmissions, emergency department presentations and urgent symptom clinic presentation at will also be recorded.DiscussionThis trial will inform design of a future definitive randomised controlled trial and implementation of prehabilitation for people receiving autologous stem cell transplant by providing data on efficacy and safety.Trial registrationThe PIRATE Trial has been approved by the Eastern Health Human Research Ethics Committee (E20/003/61055) and is funded by the Eastern Health Foundation. This trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN12620000496910. Registered April 20, 2020.

Introduction Preliminary evidence suggests that progressive resistance training may be beneficial for people with Prader-Willi Syndrome (PWS), a rare genetic condition that results in muscle weakness and low muscle tone.To establish whether community-based progressive resistance training is effective in improving the muscle strength of people with PWS; to determine cost-effectiveness; and, to complete a process evaluation assessing intervention fidelity, exploring mechanisms of impact, understanding participant experiences and identifying contextual factors affecting implementation.Methods and analysis A multisite, randomised controlled trial will be completed. Sixty participants with PWS will be randomised to receive either progressive resistance training (experimental) or non-progressive exercise (placebo control). Participants will be aged 13 to 60 years, be able to follow simple instructions in English and have no contraindications to performing progressive resistance training. The experimental group will complete progressive resistance training two times weekly for 24 weeks supervised by an exercise professional at a community gym. The control group will receive all aspects of the intervention except progressive overload. Outcomes will be assessed at week 25 (primary endpoint) and week 52 by a blinded assessor. The primary outcome is muscle strength assessed using one repetition maximum for upper limb and lower limb. Secondary outcomes are muscle mass, functional strength, physical activity, community participation, health-related quality of life and behaviour. Health economic analysis will evaluate cost-effectiveness. Process evaluation will assess safety and intervention fidelity, investigate mechanism of impact, explore participant experiences and identify contextual factors affecting implementation. Data collection commenced in February 2020 and will conclude in September 2023.Ethics and dissemination Ethical approval was obtained from The Royal Children’s Hospital Human Research Ethics Committee (HREC/50874/RCHM-2019) under the National Mutual Acceptance initiative. Research governance approvals were obtained from five clinical sites. Results will be disseminated through published manuscripts, conference presentations, public seminars and practical resources for stakeholder groups.Trial registration number ACTRN12620000416998; Australian and New Zealand Clinical Trial Registry.

Micronutrients (vitamins and minerals) have been less well studied compared to macronutrients (fats, proteins, and carbohydrates) although they play important roles in growth, metabolism, and maintenance of tissues. Hence, there is growing interest to understand the influence of micronutrients across various aspects in nutritional research. In the last two decades, aquaculture feeds have been shifted to containing more plant-based materials to meet the increasing demand and maintain the sustainability in the industry. A recent whole life cycle feeding trial of Atlantic salmon (Salmo salar) with graded levels of micronutrient packages has concluded that the levels of several B-vitamins and microminerals need to be increased from the current recommendation levels for optimal growth and fish welfare when plant-based diets are used. Here, we show the effect of micronutrient supplementation on hepatic transcriptional and epigenetic regulation in a dose dependent manner. . Specifically, our aim is to reveal the mechanisms of altered cell metabolism, which results in improved growth performance by micronutrient surpluses, at gene expression and DNA methylation levels. Our results strongly indicate that micronutrient supplementation suppresses gene expression in lipid metabolism in a dose-dependent manner and broadly affects DNA methylation in cell-adhesion and cell-signalling. In particular, it increases DNA methylation levels on the acetyl-CoA carboxylase alpha promoter in a concentration-dependent manner, which further suggests that acetyl-CoA carboxylase alpha is an upstream epigenetic regulator controlling its downstream lipid biosynthesis activities. This study demonstrates a comprehensive analysis to reveal an important role of micronutrients in lipid metabolism through epigenetic control of gene expression.

BackgroundIncreasing participation in physical activity has the potential to improve outcomes for children and adolescents with cancer during treatment and into survivorship. The aim of this study is to outline the theoretical process behind development of CanMOVE, a behavior change intervention designed to increase physical activity for children and adolescents with cancer.Study designThis study followed a theoretical design process consistent with the Behavior Change Wheel to inform the design of a complex intervention.Materials and methodsThe three stages of the Behavior Change Wheel intervention design process include: (1) understanding physical activity behavior within the pediatric cancer setting, (2) identifying potential intervention functions, and (3) identifying appropriate behavior change and implementation strategies. Qualitative and behavior change literature relevant to the pediatric cancer treatment setting were used to inform each stage.ResultsAn individualized and flexible approach to physical activity promotion that considers intrinsic factors specific to the child/adolescent and their environment is required. Fifteen behavioral change strategies were identified to form the intervention components of CanMOVE. Implementation strategies were identified to build motivation, opportunity and capacity toward increasing physical activity behaviors. Key intervention components of CanMOVE include standardized assessment and monitoring (physical activity, physical function, and health-related quality of life), provision of an activity monitor to both child/adolescent and parent, and one-on-one capacity building sessions with a healthcare professional. Capacity building sessions include education, goal setting, an active supervised physical activity session, barrier identification and problem solving, and action planning.ConclusionCanMOVE is a novel approach to physical activity promotion in the pediatric cancer treatment setting. The use of a theoretical intervention design process will aid evaluation and replication of CanMOVE when it is assessed for feasibility in a clinical setting. The design process utilized here can be used as a guide for future intervention development.

Abstract Background Ensuring patients receive an effective dose of therapeutic exercises and activities is a significant challenge for inpatient rehabilitation. My Therapy is a self-management program which encourages independent practice of occupational therapy and physiotherapy exercises and activities, outside of supervised therapy sessions. Methods This implementation trial aims to determine both the clinical effectiveness of My Therapy on the outcomes of function and health-related quality of life, and cost-effectiveness per minimal clinically important difference (MCID) in functional independence achieved and per quality adjusted life year (QALY) gained, compared to usual care. Using a stepped-wedge cluster randomised design, My Therapy will be implemented across eight rehabilitation wards (inpatient and home-based) within two public and two private Australian health networks, over 54-weeks. We will include 2,160 patients aged 18 + years receiving rehabilitation for any diagnosis. Each ward will transition from the usual care condition (control group receiving usual care) to the experimental condition (intervention group receiving My Therapy in addition to usual care) sequentially at six-week intervals. The primary clinical outcome is achievement of a MCID in the Functional Independence Measure (FIM™) at discharge. Secondary outcomes include improvement in quality of life (EQ-5D-5L) at discharge, length of stay, 30-day re-admissions, discharge accommodation, follow-up rehabilitation services and adverse events (falls). The economic outcomes are the cost-effectiveness per MCID in functional independence (FIM™) achieved and per QALY gained, for My Therapy compared to usual care, from a health-care sector perspective. Cost of implementation will also be reported. Clinical outcomes will be analysed via mixed-effects linear or logistic regression models, and economic outcomes will be analysed via incremental cost-effectiveness ratios. Discussion The My Therapy implementation trial will determine the effect of adding self-management within inpatient rehabilitation care. The results may influence health service models of rehabilitation including recommendations for systemic change to the inpatient rehabilitation model of care to include self-management. Findings have the potential to improve patient function and quality of life, and the ability to participate in self-management. Potential health service benefits include reduced hospital length of stay, improved access to rehabilitation and reduced health service costs. Trial registration This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000313831; registered 22/03/2021, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380828&isReview=true ).

Abstract Background Process evaluations have been recommended alongside clinical and economic evaluations to enable an in-depth understanding of factors impacting results. My Therapy is a self-management program designed to augment usual care inpatient rehabilitation through the provision of additional occupational therapy and physiotherapy exercises and activities, for the patient to complete outside of supervised therapy. The aims of the process evaluation are to assess the implementation process by investigating fidelity, quality of implementation, acceptability, adoption, appropriateness, feasibility and adaptation of the My Therapy intervention; and identify contextual factors associated with variations in outcomes, including the perspectives and experiences of patients and therapists. Methods The process evaluation will be conducted alongside the clinical and economic evaluation of My Therapy, within eight rehabilitation wards across two public and two private Australian health networks. All participants of the stepped wedge cluster randomised trial (2,160 rehabilitation patients) will be included in the process evaluation (e.g., ward audit); with a subset of 120 participants undergoing more intensive evaluation (e.g., surveys and activity logs). In addition, 24 staff (occupational therapists and physiotherapists) from participating wards will participate in the process evaluation. The mixed-methods study design will adopt a range of quantitative and qualitative research approaches. Data will be collected via a service profile survey and audits of clinical practice across the participating wards (considering areas such as staffing profiles and prescription of self-management programs). The intensive patient participant data collection will involve structured therapy participation and self-management program audits, Exercise Self Efficacy Scale, patient activity logs, patient surveys, and patient-worn activity monitors. Staff data collection will include surveys and focus groups. Discussion The process evaluation will provide context to the clinical and economic outcomes associated with the My Therapy clinical trial. It considers how clinical and economic outcomes were achieved, and how to sustain the outcomes within the participating health networks. It will also provide context to inform future scaling of My Therapy to other health networks, and influence future models of rehabilitation and related policy. Trial registration This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000313831; registered 22/03/2021, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380828&isReview=true ).

Abstract Introduction There is growing interest in developing research culture and opportunities for allied health professionals working in medical imaging. However, little attention has been given to identifying the research interest and needs of this group relative to the other allied health professions. We aimed to measure self‐reported research participation, interest, experience and confidence of allied health professionals working in medical imaging and compare the findings to clinicians working in allied health therapies. Methods A cross‐sectional survey of allied health professionals from medical imaging (radiographers, sonographers and nuclear medicine technologists) was conducted. The primary outcome, the Research Spider survey, measures 10 domains of research interest/experience/confidence on a 5‐point Likert scale. Results were compared to allied health therapy data. Results Responses were received by 82 medical imaging allied health professionals (65% response rate). Overall, medical imaging professionals rated themselves as having ‘some interest’ and ‘little experience or confidence’ in research. There was no difference in interest, experience and confidence among different imaging professions (interest P = 0.099, experience P = 0.380, confidence P = 0.212) or allied health therapists (interest P = 0.137, experience P = 0.363, confidence P = 0.791). Participants reported greatest interest in finding and reviewing literature and lowest interest in applying for funding. Conclusion There are strong similarities between medical imaging allied health professionals and allied health therapy professionals. Therefore, strategies used to promote research culture in allied health therapy professions could be leveraged to provide opportunities for medical imaging allied health professionals.

Enzyme reaction networks can control the spatial and temporal formation of hydrogels. Here, inspired by biofilm formation, urease-containing particles create a propagating pH gradient which induces thiol-acrylate polymerization, with properties tuned by solution viscosity, particle dimensions, and spatial configuration.

BackgroundAccess to rehabilitation to support cancer survivors to exercise is poor. Group exercise–based rehabilitation may be delivered remotely, but no trials have currently evaluated their efficacy. ObjectiveWe aimed to evaluate the efficacy of a group exercise–based cancer rehabilitation program delivered via telehealth compared to usual care for improving the quality of life of cancer survivors. MethodsA parallel, assessor-blinded, pragmatic randomized controlled trial with embedded cost and qualitative analysis will be completed. In total, 116 cancer survivors will be recruited from a metropolitan health network in Melbourne, Victoria, Australia. The experimental group will attend an 8-week, twice-weekly, 60-minute exercise group session supervised via videoconferencing supplemented by a web-based home exercise program and information portal. The comparison group will receive usual care including standardized exercise advice and written information. Assessments will be completed at weeks 0 (baseline), 9 (post intervention), and 26 (follow-up). The primary outcome will be health-related quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at week 9. Secondary measures include walking capacity (6-minute walk test), physical activity (activPAL accelerometer), self-efficacy (Health Action Process Approach Questionnaire), and adverse events. Health service data including hospital length of stay, hospital readmissions, and emergency department presentations will be recorded. Semistructured interviews will be completed within an interpretive description framework to explore the patient experience. The primary outcome will be analyzed using linear mixed effects models. A cost-effectiveness analysis will also be performed. ResultsThe trial commenced in April 2022. As of June 2022, we enrolled 14 participants. ConclusionsThis trial will inform the future implementation of cancer rehabilitation by providing important data about efficacy, safety, cost, and patient experience. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621001417875; https://tinyurl.com/yc5crwtr International Registered Report Identifier (IRRID)PRR1-10.2196/38553

Abstract Bovine Respiratory Syncytial Virus (BRSV) is a primary viral cause of Bovine Respiratory Disease (BRD) in young calves, which is responsible for substantial morbidity and mortality. Infection with BRSV induces global gene expression changes in respiratory tissues. If these changes are observed in tissues which are more accessible in live animals, such as whole blood, they may be used as biomarkers for diagnosis of the disease. Therefore, the objective of the current study was to elucidate the whole blood transcriptomic response of dairy calves to an experimental challenge with BRSV. Calves (Holstein–Friesian) were either administered BRSV inoculate (103.5 TCID50/ml × 15 ml) (n = 12) or sterile phosphate buffered saline (n = 6). Clinical signs were scored daily and whole blood was collected in Tempus RNA tubes immediately prior to euthanasia, at day 7 post-challenge. RNA was extracted from blood and sequenced (150 bp paired-end). The sequence reads were aligned to the bovine reference genome (UMD3.1) and EdgeR was subsequently employed for differential gene expression analysis. Multidimensional scaling showed that samples from BRSV challenged and control calves segregated based on whole blood gene expression changes, despite the BRSV challenged calves only displaying mild clinical symptoms of the disease. There were 281 differentially expressed (DE) genes (p 2) between the BRSV challenged and control calves. The top enriched KEGG pathways and gene ontology terms were associated with viral infection and included “Influenza A”, “defense response to virus”, “regulation of viral life cycle” and “innate immune response”. Highly DE genes involved in these pathways may be beneficial for the diagnosis of subclinical BRD from blood samples.

There is a need to ensure that healthcare organisations enable their workforces to use digital methods in service delivery. This study aimed to evaluate the current level of digital understanding and ability in nursing, midwifery, and allied health workforces and identify some of the training requirements to improve digital literacy in these health professionals. Representatives from eight healthcare organizations in Victoria, Australia participated in focus groups. Three digital frameworks informed the focus group topic guide that sought to examine the barriers and enablers to adopting digital healthcare along with training requirements to improve digital literacy. Twenty-three participants self-rated digital knowledge and skills using Likert scales and attended the focus groups. Mid-range scores were given for digital ability in nursing, midwifery, and allied health professionals. Focus group participants expressed concern over the gap between their organizations’ adoption of digital methods relative to their digital ability, and there were concerns about cyber security. Participants also saw a need for the inclusion of consumers in digital design. Given the widening gap between digital innovation and health workforce digital capability, there is a need to accelerate digital literacy by rapidly deploying education and training and policies and procedures for digital service delivery.

Abstract Background Bovine Respiratory Syncytial Virus (BRSV) is a cause of Bovine Respiratory Disease (BRD). DNA-based biomarkers contributing to BRD resistance are potentially present in non-protein-coding regulatory regions of the genome, which can be determined using ATAC-Seq. The objectives of this study were to: (i) identify regions of open chromatin in DNA extracted from bronchial lymph nodes (BLN) of healthy dairy calves experimentally challenged with BRSV and compare them with those from non-challenged healthy control calves, (ii) elucidate the chromatin regions that were differentially or uniquely open in the BRSV challenged relative to control calves, and (iii) compare the genes found in regions proximal to the differentially open regions to the genes previously found to be differentially expressed in the BLN in response to BRSV and to previously identified BRD susceptibility loci. This was achieved by challenging clinically healthy Holstein-Friesian calves (mean age 143 ± 14 days) with either BRSV inoculum (n = 12) or with sterile phosphate buffered saline (PBS) (n = 6) and preparing and sequencing ATAC-Seq libraries from fresh BLN tissues. Results Using Diffbind, 9,144 and 5,096 differentially accessible regions (P

Osteoid osteomas are benign, typically intracortical lesions most often affecting the diaphyses of long bones. We describe a case involving a 26-year-old male laborer who presented with the insidious onset of ulnar-sided wrist pain. He was diagnosed with and successfully treated with surgical excision for an osteoid osteoma involving the hook of the hamate.

BackgroundAccess to exercise therapy for cancer survivors is poor. Professional development to support exercise professionals in delivering these interventions is needed. Few online resources exist for exercise professionals to address this issue. ObjectiveTo develop and evaluate a freely available online toolkit to support exercise professionals working with cancer survivors. MethodsA 2-phase, experience-based co-design approach was used to develop and evaluate the online toolkit. The two phases were as follows: 1) needs identification and co-design of resources and platform and 2) pilot evaluation. Four co-design workshops were conducted, transcribed, and thematically analyzed to identify key elements for the toolkit. For the pilot evaluation, a customized survey (the Determinants of Implementation Behavior Questionnaire) was distributed to exercise professionals at baseline and 3 months after launch of the online toolkit to determine its usability, utility, and effectiveness in improving their knowledge, confidence, and behavior. Results were reported as the median and interquartile range and changes were calculated using non-parametric tests. Website analytics described site usage after the initial evaluation. ResultsTwenty-five exercise professionals participated in co-designing 8 key elements of the online Cancer Exercise Toolkit: the homepage and pages for getting started, screening and safety, assessment, exercise prescription, education, locations, and resources. For the pilot evaluation, 277/320 respondents (87% of whom were physiotherapists) from 26 countries completed the survey at baseline, with 58 exercise professionals completing follow-up surveys at 3 months. Exercise professionals’ knowledge, skills, and confidence in delivering exercise therapy to cancer survivors increased 3 months after baseline (items 1, 6, and 8: median score 5, IQR 3 to 6) to follow-up (items 1 and 6: median score 6, IQR 5 to 6; item 8: median score 5, IQR 5 to 7; P

Abstract Background Timely access is a challenge for providers of outpatient and community-based health services, as seen by the often lengthy waiting lists to manage demand. The Specific Timely Appointments for Triage (STAT) model, an alternative approach for managing access and triage, reduced waiting time by 34% in a stepped wedge cluster randomised controlled trial involving 8 services and more than 3000 participants. Follow up periods ranged from 3 to 10 months across the participating services in accordance with the stepped wedge design. This study aimed to determine whether outcomes were sustained for a full 12 months after implementation of the STAT model at each site. Methods Routinely collected service data were obtained for a total of 12 months following implementation of the STAT model at each of the 8 services that participated in a stepped wedge cluster randomised controlled trial. The primary outcome was time to first appointment. Secondary outcomes included non-attendance rates, time to second appointment and service use over 12 weeks. Outcomes were compared to pre-intervention data from the original trial, modelled using generalised linear mixed effects models accounting for clustering of sites. Results A 29% reduction in waiting time could be attributed to STAT over 12 months, compared to 34% in the original trial. A reduction in variability in waiting time was sustained. There were no significant changes in time to second appointment or in the number of missed appointments in the extended follow up period. Conclusions STAT is an effective strategy for reducing waiting time in community-based outpatient services. At 12 months, small reductions in the overall effect are apparent, but reductions in variability are sustained, suggesting that people who previously waited the longest benefit most from the STAT model. Trial registration This is a 12-month follow up of a stepped wedge cluster randomised controlled trial that was registered with the Australia and New Zealand Clinical Trials Registry ( ACTRN12615001016527 ).

Abstract Background Allied health assistants (AHAs) are support staff who complete clinical and non-clinical tasks under the supervision and delegation of an allied health professional. The effect of allied health professional delegation of clinical tasks to AHAs on patient and healthcare organisational outcomes is unknown. The purpose of this systematic review was to investigate the effect of allied health professional delegation of therapy to AHAs on patient and organisational outcomes. Methods A systematic review and meta-analysis was conducted. Databases MEDLINE (Ovid), Embase (Ovid), Informit (all databases), Emcare (Ovid), PsycINFO (Ovid), Cumulative Index to Nursing and Allied Health Literature [CINAHL] (EbscoHost) and the Cochrane Database of Systematic Reviews were searched from earliest date available. Additional studies were identified by searching reference lists and citation tracking. Two reviewers independently applied inclusion and exclusion criteria. The quality of the study was rated using internal validity items from the Downs and Black checklist. Risk ratios (RR) and mean differences (MD) were calculated for patient and organisational outcomes. Meta-analyses were conducted using the inverse variance method and random-effects model. Results Twenty-two studies met the inclusion criteria. Results of meta-analysis provided low quality evidence that AHA supervised exercise in addition to usual care improved the likelihood of patients discharging home (RR 1.28, 95%CI 1.03 to 1.59, I2 = 60%) and reduced length of stay (MD 0.28 days, 95%CI 0.03 to 0.54, I2 = 0%) in an acute hospital setting. There was preliminary evidence from one high quality randomised controlled trial that AHA provision of nutritional supplements and assistance with feeding reduced the risk of patient mortality after hip fracture (RR 0.41, 95%CI 0.16 to 1.00). In a small number of studies (n = 6) there was no significant difference in patient and organisational outcomes when AHA therapy was substituted for therapy delivered by an allied health professional. Conclusion We found preliminary evidence to suggest that the use of AHAs to provide additional therapy may be effective for improving some patient and organisational outcomes. Review registration CRD42019127449 .

Objective: To test the feasibility, safety and effectiveness of the My Therapy programme for inpatients with mild-moderate cognitive impairment. Design: Observational pilot study. Patients: Rehabilitation inpatients with mild-moderate cognitive impairment. Methods: During their inpatient admission, participants received My Therapy, a programme that can increase the dose of rehabilitation through independent self-practice of exercises, outside of supervised therapy. Outcomes included My Therapy participation, falls, Functional Independence Measure (FIM) and 10-m walk test. Outcomes were compared with those of participants without cognitive impairment from the original My Therapy study (n = 116) using χ2 and independent t-tests. Results: Eight participants with mild-moderate cognitive impairment (mean (standard deviation (SD)) age 89.6 years (4.8); 3 women) were included. All participants completed the My Therapy programme on at least one day of their admission, with no associated falls. Participants had an 8.4 s (SD 5.1) reduction in their 10-m walk test and a 21.5 point (SD 11.1) improvement on FIM scores from admission to discharge. There were no significant between-group differences in feasibility, safety or effectiveness for participants with and without cognitive impairment. Conclusion: This pilot study has shown that including exercise self-management as part of inpatient rehabilitation is feasible, safe and effective for patients with cognitive impairment. Lay Abstract This study aimed to determine whether it was practical, safe and effective for patients in a rehabilitation hospital with memory or thinking problems to participate in a programme called My Therapy. My Therapy aimed to increase the dose of rehabilitation through independent self-practice of exercises, outside of supervised therapy sessions. There were 8 participants in the study and all of them reported completing the My Therapy programme on at least one day of their rehabilitation stay. There were no falls relating to My Therapy participation. Participants improved their walking speed and function during their rehabilitation stay. There were no differences in the results between people with and without memory or thinking problems, in terms of practicality, safety or effectiveness. This study has shown that including exercise self-management as part of rehabilitation is practical, safe and effective for patients with memory or thinking problems.

Abstract Background During the last decade, the use of common-variant array-based single nucleotide polymorphism (SNP) genotyping in the beef and dairy industries has produced an astounding amount of medium-to-low density genomic data. Although low-density assays work well in the context of genomic prediction, they are less useful for detecting and mapping causal variants and the effects of rare variants are not captured. The objective of this project was to maximize the accuracies of genotype imputation from medium- and low-density assays to the marker set obtained by combining two high-density research assays (~ 850,000 SNPs), the Illumina BovineHD and the GGP-F250 assays, which contains a large proportion of rare and potentially functional variants and for which the assay design is described here. This 850 K SNP set is useful for both imputation to sequence-level genotypes and direct downstream analysis. Results We found that a large multi-breed composite imputation reference panel that includes 36,131 samples with either BovineHD and/or GGP-F250 genotypes significantly increased imputation accuracy compared with a within-breed reference panel, particularly at variants with low minor allele frequencies. Individual animal imputation accuracies were maximized when more genetically similar animals were represented in the composite reference panel, particularly with complete 850 K genotypes. The addition of rare variants from the GGP-F250 assay to our composite reference panel significantly increased the imputation accuracy of rare variants that are exclusively present on the BovineHD assay. In addition, we show that an assay marker density of 50 K SNPs balances cost and accuracy for imputation to 850 K. Conclusions Using high-density genotypes on all available individuals in a multi-breed reference panel maximized imputation accuracy for tested cattle populations. Admixed animals or those from breeds with a limited representation in the composite reference panel were still imputed at high accuracy, which is expected to further increase as the reference panel expands. We anticipate that the addition of rare variants from the GGP-F250 assay will increase the accuracy of imputation to sequence level.

Abstract Background Clinical supervision is recommended for allied health professionals for the purpose of supporting them in their professional role, continued professional development and ensuring patient safety and high quality care. The aim of this mixed methods study was to explore allied health professionals’ perceptions about the aspects of clinical supervision that can facilitate effective clinical supervision. Methods Individual semi-structured interviews were conducted on a purposive sample of 38 allied health professionals working in a metropolitan public hospital. Qualitative analysis was completed using an interpretive description approach. To enable triangulation of qualitative data, a quantitative descriptive survey of clinical supervision effectiveness was also conducted using the Manchester Clinical Supervision Scale (MCSS-26). Results Three main themes emerged from qualitative analysis: Allied health professionals reported that clinical supervision was most effective when their professional development was the focus of clinical supervision; the supervisor possessed the skills and attributes required to facilitate a constructive supervisory relationship; and the organisation provided an environment that facilitated this relationship together with their own professional development. Three subthemes also emerged within each of the main themes: the importance of the supervisory relationship; prioritisation of clinical supervision relative to other professional duties; and flexibility of supervision models, processes and approaches to clinical supervision. The mean MCSS-26 score was 79.2 (95%CI 73.7 to 84.3) with scores ranging from 44 to 100. MCSS-26 results converged with the qualitative findings with participants reporting an overall positive experience with clinical supervision. Conclusions The factors identified by allied health professionals that influenced the effectiveness of their clinical supervision were mostly consistent among the professions. However, allied health professionals reported using models of clinical supervision that best suited their profession’s role and learning style. This highlighted the need for flexible approaches to allied health clinical supervision that should be reflected in clinical supervision policies and guidelines. Many of the identified factors that influence the effectiveness of clinical supervision of allied health professionals can be influenced by health organisations.

BackgroundAccess to exercise for cancer survivors is poor despite global recognition of its benefits. Telerehabilitation may overcome barriers to exercise for cancer survivors but is not routinely offered. ObjectiveFollowing the rapid implementation of an exercise-based telerehabilitation program in response to COVID-19, a process evaluation was conducted to understand the impact on patients, staff, and the health service with the aim of informing future program development. MethodsA mixed methods evaluation was completed for a telerehabilitation program for cancer survivors admitted between March and December 2020. Interviews were conducted with patients and staff involved in implementation. Routinely collected hospital data (adverse events, referrals, admissions, wait time, attendance, physical activity, and quality of life) were also assessed. Patients received an 8-week telerehabilitation intervention including one-on-one health coaching via telehealth, online group exercise and education, information portal, and home exercise prescription. Quantitative data were reported descriptively, and qualitative interview data were coded and mapped to the Proctor model for implementation research. ResultsThe telerehabilitation program received 175 new referrals over 8 months. Of those eligible, 123 of 150 (82%) commenced the study. There were no major adverse events. Adherence to health coaching was high (674/843, 80% of scheduled sessions), but participation in online group exercise classes was low (n=36, 29%). Patients improved their self-reported physical activity levels by a median of 110 minutes per week (IQR 90-401) by program completion. Patients were satisfied with telerehabilitation, but clinicians reported a mixed experience of pride in rapid care delivery contrasting with loss of personal connections. The average health service cost per patient was Aus $1104 (US $790). ConclusionsTelerehabilitation is safe, feasible, and improved outcomes for cancer survivors. Learnings from this study may inform the ongoing implementation of cancer telerehabilitation.

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.