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Abstract Background Having a primary care provider is associated with better care experiences and lower care costs. In 2021, INSPIRE-PHC released Primary Care Data Reports - publicly available summaries of administrative billing data about how populations in each of Ontario’s 60 health teams use primary care services. Given the characterization of Canadian primary care systems as ‘in crisis’, publicly available data about primary care at the regional level presented a significant opportunity for knowledge mobilization. An understandable resource could ground the public conversation about primary care access in data. Recognizing the role that lived experience plays in ensuring the public understands research findings, a partnership between patient advisors, Ontario Health Team representatives, researchers, and trainees was established to co-produce public-facing infographics based on primary care data. Methods Evidence-based guidelines for public health infographic creation and elements of transformative action research guided a six-meeting process to engage up to 14 patient advisors, three Ontario Health Team staff and two primary care trainees. Patient advisors were affiliated with a provincial patient-oriented primary health care research group or a Hamilton-based Ontario Health Team. Ninety-minute meetings were conducted virtually, and notes were shared with attendees to ensure they accurately reflected the conversation. Two consultations with Ontario Health Team-affiliated primary care providers provided direction and ensured project outputs aligned with local priorities. Results Project partners shared feedback on draft infographics, audience identification, priority elements from Primary Care Data Reports to include in the infographics, and aesthetic features (e.g., headings, colour scheme, charts). Project partners felt the most important metrics to convey to the public were those that simultaneously reinforced the benefits of primary care on individual health outcomes and health system costs. Conclusions Patient engagement in research is becoming widespread, but co-developing knowledge products with patient and health system partners is less common. Our approach to engaging patients prevented both oversimplification and unnecessary complexity in a public-facing visual about attachment to primary care.

Abstract Background Despite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers. Methods We designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test. Results The dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn’t develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models. Conclusions This methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy. Graphical Abstract

Abstract Salmonella forms biofilms, and persist on food contact surfaces. Once a biofilm is formed cleaning and sanitation protocols may be inadequate for effective removal. This study evaluated attachment characteristics, surface properties, and structure of Salmonella biofilms on food contact surfaces commonly used in the tree-fruit industry. Multi-strain Salmonella biofilms were grown in a Centers for Disease Control and Prevention (CDC) biofilm reactor at 22 ± 2 °C and sampling was conducted at 2, 24 and 96-h. After each incubation period, coupons weregently rinsed and the remaining cells enumerated. Biofilms were analyzed with Laser Scanning Confocal Microscopy (LSCM). Hydrophobicity was evaluated by measuring the contact angles of reference liquids method using a drop tensiometer instrument. Material type and biofilm age significantly influenced attachment and biofilm hydrophobicity (P

Abstract Background Near-peer teaching is a popular pedagogical teaching tool however many existing models fail to demonstrate benefits in summative OSCE performance. The 3-step deconstructed (3-D)skills near-peer model was recently piloted in undergraduate medicine showing short term improvement in formative OSCE performance utilising social constructivist educational principles. This study aims to assess if 3-D skills model teaching affects summative OSCE grades. Methods Seventy-nine third year medical students attended a formative OSCE event at the University of Glasgow receiving an additional 3-minutes per station of either 3-D skills teaching or time-equivalent unguided practice. Students’ summative OSCE results were compared against the year cohort to establish whether there was any difference in time delayed summative OSCE performance. Results 3-D skills and unguided practice cohorts had comparable demographical data and baseline formative OSCE performance. Both the 3-D skill cohort and unguided practice cohort achieved significantly higher median station pass rates at summative OSCEs than the rest of the year. This correlated to one additional station pass in the 3-D skills cohort, which would increase median grade banding from B to A. The improvement in the unguided practice cohort did not achieve educational significance. Conclusion Incorporating the 3-D skills model into a formative OSCE is associated with significantly improved performance at summative OSCEs. This expands on the conflicting literature for formative OSCE sessions which have shown mixed translation to summative performance and suggests merit in institutional investment to improve clinical examination skills.

Abstract Background The purpose of this paper is to report on the process for developing an online RE-AIM evaluation toolkit in partnership with organizations that provide physical activity programming for persons with disabilities. Methods A community-university partnership was established and guided by an integrated knowledge translation approach. The four-step development process included: (1) identify, review, and select knowledge (literature review and two rounds of Delphi consensus-building), (2) adapt knowledge to local context (rating feasibility of outcomes and integration into online platform), (3) assess barriers and facilitators (think-aloud interviews), and (4) select, tailor, implement (collaborative dissemination plan). Results Step 1: Fifteen RE-AIM papers relevant to community programming were identified during the literature review. Two rounds of Delphi refined indicators for the toolkit related to reach, effectiveness, adoption, implementation, and maintenance. Step 2: At least one measure was linked with each indicator. Ten research and community partners participated in assessing the feasibility of measures, resulting in a total of 85 measures. Step 3: Interviews resulted in several recommendations for the online platform and toolkit. Step 4: Project partners developed a dissemination plan, including an information package, webinars, and publications. Discussion This project demonstrates that community and university partners can collaborate to develop a useful, evidence-informed evaluation resource for both audiences. We identified several strategies for partnership when creating a toolkit, including using a set of expectations, engaging research users from the outset, using consensus methods, recruiting users through networks, and mentorship of trainees. The toolkit can be found at et.cdpp.ca. Next steps include disseminating (e.g., through webinars, conferences) and evaluating the toolkit to improve its use for diverse contexts (e.g., universal PA programming).

Abstract Background The Stop Cancer PAIN Trial was a phase III pragmatic stepped wedge cluster randomised controlled trial which compared effectiveness of screening and guidelines with or without implementation strategies for improving pain in adults with cancer attending six Australian outpatient comprehensive cancer centres (n = 688). A system for pain screening was introduced before observation of a ‘control’ phase. Implementation strategies introduced in the ‘intervention’ phase included: (1) audit of adherence to guideline recommendations, with feedback to clinical teams; (2) health professional education via an email-administered ‘spaced education’ module; and (3) a patient education booklet and self-management resource. Selection of strategies was informed by the Capability, Opportunity and Motivation Behaviour (COM-B) Model (Michie et al., 2011) and evidence for each strategy’s stand-alone effectiveness. A consultant physician at each centre supported the intervention as a ‘clinical champion’. However, fidelity to the intervention was limited, and the Trial did not demonstrate effectiveness. This paper reports a sub-study of the Trial which aimed to identify factors inhibiting or enabling fidelity to inform future guideline implementation initiatives. Methods The qualitative sub-study enabled in-depth exploration of factors from the perspectives of personnel at each centre. Clinical champions, clinicians and clinic receptionists were invited to participate in semi-structured interviews. Analysis used a framework method and a largely deductive approach based on the COM-B Model. Results Twenty-four people participated, including 15 physicians, 8 nurses and 1 clinic receptionist. Coding against the COM-B Model identified ‘capability’ to be the most influential component, with ‘opportunity’ and ‘motivation’ playing largely subsidiary roles. Findings suggest that fidelity could have been improved by: considering the readiness for change of each clinical setting; better articulating the intervention’s value proposition; defining clinician roles and responsibilities, addressing perceptions that pain care falls beyond oncology clinicians’ scopes of practice; integrating the intervention within existing systems and processes; promoting patient-clinician partnerships; investing in clinical champions among senior nursing and junior medical personnel, supported by medical leaders; and planning for slow incremental change rather than rapid uptake. Conclusions Future guideline implementation interventions may require a ‘meta-implementation’ approach based on complex systems theory to successfully integrate multiple strategies. Trial registration Registry: Australian New Zealand Clinical Trials Registry; number: ACTRN 12615000064505; data: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspxid=367236&isReview=true .

Abstract Background The Safer Baby Bundle (SBB) aimed to reduce stillbirth rates in Australia through improving pregnancy care across five elements; smoking cessation, fetal growth restriction (FGR), decreased fetal movements (DFM), side sleeping in late pregnancy and decision making around timing of birth. We assessed experiences of women and healthcare professionals (HCPs) with antenatal care practices around the five elements. Methods A pre-post study design using online surveys was employed to assess change in HCPs awareness, knowledge, and frequency of performing recommended practices (22 in total) and women’s experiences of care received related to reducing their chance of stillbirth. Women who had received antenatal care and HCPs (midwives and doctors) at services participating in the SBB implementation program in two Australian states were invited to participate. Surveys were distributed over January to July 2020 (pre) and August to December 2022 (post). Comparison of pre-post responses was undertaken using Fisher’s exact, Pearson’s chi-squared or Wilcoxon rank-sum tests. Results 1,225 women (pre-1096/post-129) and 1,415 HCPs (pre-1148/post-267, ≥ 83% midwives) completed the surveys. The frequency of HCPs performing best practice ‘all the time’ significantly improved post-SBB implementation across all elements including providing advice to women on side sleeping (20.4–79.4%, p

Abstract Background CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to generate similar gene-independent responses to CRISPR-Cas9 targeting (proximity bias), possibly due to Cas9-induced whole chromosome-arm truncations or other genomic structural features and different chromatin accessibility levels. Results We benchmarked eight computational methods, rigorously evaluating their ability to reduce both CN and proximity bias in the two largest publicly available cell-line-based CRISPR-Cas9 screens to date. We also evaluated the capability of each method to preserve data quality and heterogeneity by assessing the extent to which the processed data allows accurate detection of true positive essential genes, established oncogenetic addictions, and known/novel biomarkers of cancer dependency. Our analysis sheds light on the ability of each method to correct biases under different scenarios. AC-Chronos outperforms other methods in correcting both CN and proximity biases when jointly processing multiple screens of models with available CN information, whereas CRISPRcleanR is the top performing method for individual screens or when CN information is not available. In addition, Chronos and AC-Chronos yield a final dataset better able to recapitulate known sets of essential and non-essential genes. Conclusions Overall, our investigation provides guidance for the selection of the most appropriate bias-correction method, based on its strengths, weaknesses and experimental settings.

Abstract Background Leveraging Alzheimer’s disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. Methods We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aβ, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). Results The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. Conclusion These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity.

Abstract Background Ear and tail lesions are prevalent indicators of impaired welfare observed in pig production with different multifactorial causes. Understanding the progression of ear and tail lesions over time is important to implement preventative strategies on commercial pig farms. Therefore, this case study aimed to provide a detailed account of patterns of ear and tail lesions in pigs on a single commercial farm during the grower-finisher period. Case presentation A total of 1,676 12-week old pigs (n = 773 females and n = 903 males, all tail docked) were followed from arrival to the grower facilities until transferred to the finisher stage on a commercial pig farm in Ireland. Pigs were individually weighed and inspected for the severity of fresh ear and tail lesions (score 0–4) on transfer to the first grower (24.9 ± 5.33 kg, 12 weeks of age, n = 1,676 pigs), second grower (33.3 ± 7.04 kg, 14 weeks of age, n = 1,641 pigs), and finisher stage (60.2 ± 7.74 kg, 18 weeks of age, n = 1,626 pigs). Due to the low number of pigs with high scores, ear lesions were classified as no (score 0), mild (score 1), moderate (score 2) and severe (score ≥ 3) and tail lesions were classified as no (score 0), mild (score 1), and moderate-to-severe (score ≥ 2). Ear lesions were more prevalent than tail lesions at each inspection. There were approx. 19% of pigs with ear lesions at all three inspections but no pigs presented with tail lesions at all three inspections. When considering the specific severity categories, we observed 32 different ear lesion score combinations and 15 different tail lesion score combinations across the three inspections. Conclusion The high number of observed patterns of ear and tail lesions suggest large individual variability in lesion progression. Ear lesions were more of an issue than tail lesions and little is known about this health and welfare problem indicating that further research into causes and management strategies is needed.

Abstract Background There is an increasing need to increase simulation-based learning opportunities for vascular surgery residents in endovascular skills training. This study aims to explore the effectiveness of remote expert instructional feedback of endovascular simulation-based education, as a means of increasing training opportunities in this area for vascular surgery residents. Methods A mixed-methods study design was adopted. Twelve vascular surgery residents from Ireland were tasked with completing two endovascular renal artery procedures: one with in-person expert feedback and the other with remote instruction. Participants ranged in experience levels from second year to final year of residency. Following the training activities, interviews and a questionnaire were employed to gather information on the usefulness of remote feedback. Results There was no significant difference reported by participants using a post-event validated questionnaire between remote and in-person feedback. During the interviews, participants expressed mixed feelings about the presence of the educator while practicing, but they eventually saw no limiting factors to their practice when the trainer provided remote feedback. When receiving performance feedback remotely, clear communication and a shared knowledge of the task development are critical to success. Conclusions We believe these findings can inform the design and development of remote learning and assessment of endovascular skills training and ultimately provide increased opportunities for more skills practice for vascular surgical residents.

Abstract Background Playing Tetris is a relatively new concept when considering how to treat or prevent post-traumatic stress symptoms (PTSS). Benefits have been identified regarding how playing the game can influence traumatic memory processing and storage. However, the concept is under-explored and can potentially help populations who are at risk of and are known to experience post-traumatic stress, such as parents of preterm infants in the Neonatal Unit. The aim of the review was to establish if preterm parents playing Tetris was a feasible option to potentially minimise PTSS. Method A scoping review was conducted using PRISMA-ScR guidance. Databases searched were Cinahl, Medline and PsychInfo, over a 20 year period (2003-2023). Titles and abstracts were screened before analysis of full-text articles. A variety of clinical and experimental studies were examined, with differing trauma exposure experienced by participants. Results Thirteen articles were reviewed and four common themes identified. These were memory consolidation, playing Tetris and its effect on intrusive memories (IMs), the effect on the brain and the acceptability as a technique to minimize PTSS in clinical trials. Conclusion Tetris, in theory, is a first-aid intervention and has the potential to minimise the impact of trauma. Based on the findings of the review, Tetris has been effective in other clinical areas and deemed acceptable by participants. Therefore, Tetris is worthy of consideration for use in the population of preterm parents.

Abstract Background Diagnosis can often be recorded in electronic medical records (EMRs) as free-text or using a term with a diagnosis code. Researchers, governments, and agencies, including organisations that deliver incentivised primary care quality improvement programs, frequently utilise coded data only and often ignore free-text entries. Diagnosis data are reported for population healthcare planning including resource allocation for patient care. This study sought to determine if diagnosis counts based on coded diagnosis data only, led to under-reporting of disease prevalence and if so, to what extent for six common or important chronic diseases. Methods This cross-sectional data quality study used de-identified EMR data from 84 general practices in Victoria, Australia. Data represented 456,125 patients who attended one of the general practices three or more times in two years between January 2021 and December 2022. We reviewed the percentage and proportional difference between patient counts of coded diagnosis entries alone and patient counts of clinically validated free-text entries for asthma, chronic kidney disease, chronic obstructive pulmonary disease, dementia, type 1 diabetes and type 2 diabetes. Results Undercounts were evident in all six diagnoses when using coded diagnoses alone (2.57–36.72% undercount), of these, five were statistically significant. Overall, 26.4% of all patient diagnoses had not been coded. There was high variation between practices in recording of coded diagnoses, but coding for type 2 diabetes was well captured by most practices. Conclusion In Australia clinical decision support and the reporting of aggregated patient diagnosis data to government that relies on coded diagnoses can lead to significant underreporting of diagnoses compared to counts that also incorporate clinically validated free-text diagnoses. Diagnosis underreporting can impact on population health, healthcare planning, resource allocation, and patient care. We propose the use of phenotypes derived from clinically validated text entries to enhance the accuracy of diagnosis and disease reporting. There are existing technologies and collaborations from which to build trusted mechanisms to provide greater reliability of general practice EMR data used for secondary purposes.

Abstract Background As many patients are spending their last days in critical care units, it is essential that they receive appropriate end-of -life care. However, cultural differences, ethical dilemmas and preference practices can arise in the intensive care settings during the end of life. Limiting therapy for dying patients in intensive care is a new concept with no legal definition and therefore there may be confusion in interpreting the terms ‘no resuscitation’ and ‘comfort care’ among physicians in Middle East. Therefore, the research question is ‘What helps or hinders effective end-of-life care in adult intensive care units in Middle Eastern countries?’ Methods The authors conducted a comprehensive systematic literature review using five electronic databases. We identified primary studies from Medline, Embase, CINAHL, Psycinfo and Scopus. The team assessed the full-text papers included in the review for quality using the Joanna Briggs Institute checklist (JBI). We completed the literature search on the first of April 2022 and was not limited to a specific period. Results We identified and included nine relevant studies in the review. We identified five main themes as end-of-life care challenges and/or facilitators: organisational structure and management, (mis)understanding of end-of-life care, spirituality and religious practices for the dying, communication about end-of-life care, and the impact of the ICU environment. Conclusions This review has reported challenges and facilitators to providing end-of-life care in ICU and made initial recommendations for improving practice. These are certainly not unique to the Middle East but can be found throughout the international literature. However, the cultural context of Middle East and North Africa countries gives these areas of practice special challenges and opportunities. Further observational research is recommended to confirm or modify the results of this review, and with a view to developing and evaluating comprehensive interventions to promote end-of-life care in ICUs in the Middle East.

Abstract Background Globally, emergency departments (EDs) are overcrowded and unable to meet an ever-increasing demand for care. The aim of this study is to comprehensively review and synthesise literature on potential solutions and challenges throughout the entire health system, focusing on ED patient flow. Methods An umbrella review was conducted to comprehensively summarise and synthesise the available evidence from multiple research syntheses. A comprehensive search strategy was employed in four databases alongside government or organisational websites in March 2023. Gray literature and reports were also searched. Quality was assessed using the JBI critical appraisal checklist for systematic reviews and research syntheses. We summarised and classified findings using qualitative synthesis, the Population-Capacity-Process (PCP) model, and the input/throughput/output (I/T/O) model of ED patient flow and synthesised intervention outcomes based on the Quadruple Aim framework. Results The search strategy yielded 1263 articles, of which 39 were included in the umbrella review. Patient flow interventions were categorised into human factors, management-organisation interventions, and infrastructure and mapped to the relevant component of the patient journey from pre-ED to post-ED interventions. Most interventions had mixed or quadruple nonsignificant outcomes. The majority of interventions for enhancing ED patient flow were primarily related to the 'within-ED' phase of the patient journey. Fewer interventions were identified for the 'post-ED' phase (acute inpatient transfer, subacute inpatient transfer, hospital at home, discharge home, or residential care) and the 'pre-ED' phase. The intervention outcomes were aligned with the aim (QAIM), which aims to improve patient care experience, enhance population health, optimise efficiency, and enhance staff satisfaction. Conclusions This study found that there was a wide range of interventions used to address patient flow, but the effectiveness of these interventions varied, and most interventions were focused on the ED. Interventions for the remainder of the patient journey were largely neglected. The metrics reported were mainly focused on efficiency measures rather than addressing all quadrants of the quadruple aim. Further research is needed to investigate and enhance the effectiveness of interventions outside the ED in improving ED patient flow. It is essential to develop interventions that relate to all three phases of patient flow: pre-ED, within-ED, and post-ED.

Abstract Background Major Depressive Disorder (MDD) is a prevalent psychiatric condition and the largest contributor to disability worldwide. MDD is highly recurrent, yet little is known about the mechanisms that occur following a Major Depressive Episode (MDE) and underlie recurrence. We explored the concept of fear of depression recurrence (FoDR) and its impact on daily functioning among individuals in remission from MDD. Methods 30 participants (83% female; 37% White; Mage = 27.7, SD = 8.96) underwent semi-structured qualitative interviews. The interviews explored participants’ experiences of FoDR including the frequency, severity, content, triggers, and impact of fears and associated coping strategies. We used content analysis to analyze the transcriptions. Results Most participants (73%) reported having FoDR, with varying frequency, severity, and duration of fears. The triggers and content of participants’ fears often mirrored the symptoms (e.g., low mood, anhedonia) and consequences (e.g., job loss, social withdrawal) endured during past MDEs. Some participants reported a minimal impact of FoDR on daily functioning, whereas others reported a positive (e.g., personal growth) or negative (e.g., increased anxiety) influence. Limitations Our sample size did not allow for explorations of differences in FoDR across unique MDD subtypes or sociocultural factors. Conclusions The concept of FoDR may present a window into understanding the unique cognitive and behavioural changes that occur following MDD remission and underlie depression recurrence. Future research should aim to identify underlying individual differences and characteristics of the disorder that may influence the presence and impact of FoDR. Finally, a FoDR measure should be developed so that associations between FoDR and recurrence risk, depressive symptoms, and other indices of functioning can be determined.

Abstract Background Operating rooms (ORs) are one of the costliest units in a hospital, therefore the cumulative consequences of any kind of inefficiency in OR management lead to a significant loss of revenue for the hospital, staff dissatisfaction, and patient care disruption. One of the possible solutions to improving OR efficiency is knowing a reliable estimate of the duration of operations. The literature suggests that the current methods used in hospitals, e.g., a surgeon’s estimate for the given surgery or taking the average of only five previous records of the same procedure, have room for improvement. Methods We used over 4 years of elective surgery records (n = 52,171) from one of the major metropolitan hospitals in Australia. We developed robust Machine Learning (ML) approaches to provide a more accurate prediction of operation duration, especially in the absence of surgeon’s estimation. Individual patient characteristics and historic surgery information attributed to medical records were used to train predictive models. A wide range of algorithms such as Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were tested for predicting operation duration. Results The results show that the XGBoost model provided statistically significantly less error than other compared ML models. The XGBoost model also reduced the total absolute error by 6854 min (i.e., about 114 h) compared to the current hospital methods. Conclusion The results indicate the potential of using ML methods for reaching a more accurate estimation of operation duration compared to current methods used in the hospital. In addition, using a set of realistic features in the ML models that are available at the point of OR scheduling enabled the potential deployment of the proposed approach.

Abstract Contraceptive use has substantial implications for women’s reproductive health, motivating research on the most effective approaches to minimize inequalities in access. When women prefer to limit or delay fertility but are not using contraception, this potentially reflects demand for contraception that is not being satisfied. Current literature emphasizes a nuanced integration of supply and demand factors to better understand this gap. In this research, we examine the interconnectedness of supply and demand factors both conceptually and methodologically by augmenting existing measures of local supply with a demand-side factor—community-level preferences for contraceptive methods. Using novel data from Performance Monitoring for Action (PMA) in seven sub-Saharan African countries, we test whether the available supply of locally preferred methods at nearby service delivery points (SDP) explains variation in women’s uptake of contraception beyond the more typical measure of contraceptive stockouts. Findings from logistic regression analyses (N = 32,282) suggest that demand and supply can be understood as tightly interconnected factors which are directly affected by local social preferences. The odds of women using modern contraception increase significantly when locally preferred methods are available, and this is true even after controlling for the availability of methods in general. The new measure tested in this research centers women and their specific desires in a manner consistent with the promotion of contraceptives as an important human right.

Abstract Background Breastfeeding has long been associated with numerous benefits for both mothers and infants. While some observational studies have explored the relationship between breastfeeding and mental health outcomes in mothers and children, a systematic review of the available evidence is lacking. The purpose of this study is to systematically evaluate the association between breastfeeding and mental health disorders in mothers and children. Methods We systematically searched MEDLINE and EMBASE from inception to June 2, 2023. The inclusion criteria consisted of all studies evaluating links between breastfeeding and development of mental health disorders in children and mothers. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) while grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. A random-effects meta-analysis was used if possible, to estimate the odds ratio for the association between breastfeeding and mental health outcomes. The Mantel–Haenszel method was utilised for pooling ORs across studies. Study heterogeneity was assessed using the I 2 statistic. Results Our review identified twenty-one original study. Of these, 18 focused on the association between breastfeeding and child health, assessing depressive disorders, schizophrenia, anxiety disorders, eating disorders and borderline personality disorder. Three studies evaluated the associations between breastfeeding and maternal mental health disorders. Three studies looking at outcomes in children showed no significant association between breastfeeding and occurrence of schizophrenia later in life (OR 0.98; 95% CI 0.57–1.71; I 2 = 29%). For depressive disorders (5 studies) and anxiety disorders (3 studies), we found conflicting evidence with some studies showing a small protective effect while others found no effect. The GRADE certainty for all these findings was very low due to multiple limitations. Three studies looking at association between breastfeeding and maternal mental health, were too heterogeneous to draw any firm conclusions. Conclusions We found limited evidence to support a protective association between breastfeeding and the development of mental health disorders in children later in life. The data regarding the association between breastfeeding and maternal mental health beyond the postnatal period is also limited. The methodological limitations of the published literature prevent definitive conclusions, and further research is needed to better understand the relationship between breastfeeding and mental health in mothers and children.

Abstract Background The COVID-19 pandemic disrupted the normality of daily life for many children, their families, and schools, resulting in heightened levels of anxiety, depression, social isolation, and loneliness among young people. An integrated public health model of interventions is needed to address the problem and to safeguard the mental health and wellbeing of children. The Triple P – Positive Parenting Program is one system of parenting support with a strong evidence-base and wide international reach. When implemented as a public health approach, Triple P has demonstrated population level positive effects on child wellbeing. This study will be the first large-scale, multi-site randomised controlled trial of a newly developed, low-intensity variant of Triple P, a school-based seminar series, as a response to the impacts of the pandemic. Methods The evaluation will employ an Incomplete Batched Stepped Wedge Cluster Randomised Trial Design. At least 300 Australian primary schools, from South Australia, Queensland, and Victoria will be recruited and randomised in three batches. Within each batch, schools will be randomly assigned to either start the intervention immediately or start in six weeks. Parents will be recruited from participating schools. The Triple P seminar series includes three seminars titled: “The Power of Positive Parenting”, “Helping Your Child to Manage Anxiety”, and “Keeping your Child Safe from Bullying”. Parents will complete measures about child wellbeing, parenting, parenting self-regulation and other key intervention targets at baseline, six weeks after baseline, and 12 weeks after baseline. Intervention effectiveness will be evaluated with a Multilevel Piecewise Latent Growth Curve Modelling approach. Data collection is currently underway, and the current phase of the project is anticipated to be completed in January 2024. Discussion The findings from this study will extend the current knowledge of the effects of evidence-based parenting support delivered through brief, universally offered, low intensity, school-based parenting seminars in a post pandemic world. Trial registration The trial is registered at the Australian New Zealand Clinical Trials Registry (Trial Registration Number: ACTRN12623000852651).

Abstract Objective To develop a consumer and community involvement (CCI) strategy for the Women’s Health Research, Translation and Impact Network (WHRTN), an initiative of the Australian Health Research Alliance (AHRA). Type of program A national network, comprising representatives from 14 nationally-accredited research translation centres that aims to embed CCI at a systems level, to improve equity and health outcomes across women’s health. Methods A CCI Sub-Committee of WHRTN was established, chaired by a Consumer Advisor/Advocate. This committee invited both internal and external Consumer Advisor/Advocates to participate in a workshop, to guide the development of WHRTN’s CCI Strategy in women’s health research. Results A CCI Strategy document was written with input from workshop attendees and leading academics in women’s health and has now been implemented into WHRTN, informing all aspect of the Network’s programs and activities. Discussion Broad and early consumer involvement can facilitate meaningful partnerships between researchers and community, and enable genuine consumer contributions to research across strategy development, priority setting and undertaking research. Appropriate finances and time need to be allocated for CCI, with training in CCI a key enabler for its effective implementation.

Abstract Background Mixing pigs at weaning can compromise pig welfare and growth. Therefore, grouping littermates together may allow a diet nutrient and energy density reduction during the nursery period to reduce feed cost without affecting slaughter weight. This study investigated the combined effect of mixing and reducing dietary energy and nutrient density on growth performance, body lesions (BL), and behaviour in pigs from weaning to slaughter. Results Forty-eight litters [554 pigs, 11–12 pigs/litter; Danish Duroc × (Large White × Landrace)] were included in the trial. At 28 days of age, pigs were weaned and housed in nursery rooms in litter groups (INTACT, n = 24) or mixed with other litters and grouped by weight to reduce within-pen pig weight variation (MIXED, n = 24). A dietary regimen meeting pigs’ nutritional requirements (CON) and a low-density dietary regimen (LOW; -10% energy and protein) completed a 2 × 2 factorial arrangement (Mixing x Diet, n = 12). On day 74 of age, pigs moved to the grower-finisher accommodation without further mixing and all pigs received the CON dietary regimen. Mixing increased FCR by 4.0% during the nursery period (p = 0.003). Nursery pigs fed LOW experienced a growth retardation which was maintained until slaughter (-2.6 kg slaughter weight; p = 0.025). Initial differences in the coefficient of variation (CV) between MIXED (10.4%) and INTACT (17.6%; p

Abstract Objective Few clinical prediction models are available to clinicians to predict the recovery of patients with post-collision neck pain and associated disorders. We aimed to develop evidence-based clinical prediction models to predict (1) self-reported recovery and (2) insurance claim closure from neck pain and associated disorders (NAD) caused or aggravated by a traffic collision. Methods The selection of potential predictors was informed by a systematic review of the literature. We used Cox regression to build models in an incident cohort of Saskatchewan adults (n = 4923). The models were internally validated using bootstrapping and replicated in participants from a randomized controlled trial conducted in Ontario (n = 340). We used C-statistics to describe predictive ability. Results Participants from both cohorts (Saskatchewan and Ontario) were similar at baseline. Our prediction model for self-reported recovery included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity and headache intensity (C = 0.643; 95% CI 0.634–0.653). The prediction model for claim closure included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity, headache intensity and depressive symptoms (C = 0.637; 95% CI 0.629–0.648). Conclusions We developed prediction models for the recovery and claim closure of NAD caused or aggravated by a traffic collision. Future research needs to focus on improving the predictive ability of the models.

Abstract Introduction Sickle cell disease (SCD) in pregnancy is associated with worse maternal and neonatal outcomes. There is limited available data describing the burden and outcomes of critically ill obstetric patients affected by SCD in low-income settings. Objectives We aimed to define SCD burden and impact on mortality in critically-ill obstetric patients admitted to an urban referral hospital in Sierra Leone. We hypothesized that SCD burden is high and independently associated with increased mortality. Methods We performed a registry-based cross-sectional study from March 2020 to December 2021 in the high-dependency unit (HDU) of Princess Christian Maternity Hospital PCMH, Freetown. Primary endpoints were the proportion of patients identified in the SCD group and HDU mortality. Secondary endpoints included frequency of maternal direct obstetric complications (MDOCs) and the maternal early obstetric warning score (MEOWS). Results Out of a total of 497 patients, 25 (5.5%) qualified to be included in the SCD group. MEOWS on admission was not different between patients with and without SCD and SCD patients had also less frequently reported MDOCs. Yet, crude HDU mortality in the SCD group was 36%, compared to 9.5% in the non SCD group (P

Abstract Objective To investigate the management of subfertility and infertility among Aboriginal and Torres Strait Islander females attending Australian general practice. Methods Cross-sectional study of 1,258,581 women (18–49 years) attending general practice between January 2011 and June 2019, utilising data from NPS MedicineWise MedicineInsight, a national general practice database in Australia. Results The prevalence of subfertility/infertility encounters was lower for Aboriginal and Torres Strait Islander females (12.37 per 1,000) than for non-Indigenous females (16.62 per 1,000). Aboriginal and Torres Strait Islander females with a subfertility/infertility encounter were younger and more likely to live outside Major cities and in areas of socioeconomic disadvantage than non-Indigenous females. Rates of prescribed infertility medications were not different between groups, however Aboriginal and Torres Strait Islander females were more likely to receive a pelvic ultrasound (24.30% vs. 19.90%); tests for luteinizing hormone (31.89% vs. 25.65%); testosterone (14.93% vs. 9.96%) and; glycated haemoglobin (HbA1c) (6.32% vs. 3.41%),but less likely to receive an anti-müllerian hormone test (2.78% vs. 7.04%). Conclusions Lower encounter rates for infertility/subfertility among Aboriginal and Torres Strait Islander peoples may indicate access issues, preferred use of Aboriginal community-controlled health centres or younger average age at first birth and thus less age-related infertility. Implications for public health Future efforts should focus on maximising the inclusiveness of infertility surveillance. There is also a need for further research into the experiences of and preferences for infertility care and associated barriers among Aboriginal and Torres Strait Islander people.

Abstract Almost 30% of live births in England and Wales occur late preterm or early term (LPET) and are associated with increased risks of adverse health outcomes throughout the lifespan. However, very little is known about the decision-making processes concerning planned LPET births or the involvement of parents in these. This aim of this paper is to review the evidence on parental involvement in obstetric decision-making in general, to consider what can be extrapolated to decisions about LPET delivery, and to suggest directions for further research. A comprehensive, narrative review of relevant literature was conducted using Medline, MIDIRS, PsycInfo and CINAHL databases. Appropriate search terms were combined with Boolean operators to ensure the following broad areas were included: obstetric decision-making, parental involvement, late preterm and early term birth, and mode of delivery. This review suggests that parents’ preferences with respect to their inclusion in decision-making vary. Most mothers prefer sharing decision-making with their clinicians and up to half are dissatisfied with the extent of their involvement. Clinicians’ opinions on the limits of parental involvement, especially where the safety of mother or baby is potentially compromised, are highly influential in the obstetric decision-making process. Other important factors include contextual factors (such as the nature of the issue under discussion and the presence or absence of relevant medical indications for a requested intervention), demographic and other individual characteristics (such as ethnicity and parity), the quality of communication; and the information provided to parents. This review highlights the overarching need to explore how decisions about potential LPET delivery may be reached in order to maximise the satisfaction of mothers and fathers with their involvement in the decision-making process whilst simultaneously enabling clinicians both to minimise the number of LPET births and to optimise the wellbeing of women and babies.

Abstract Background Across the European Union (EU), efforts are being made to achieve modernisation and harmonisation of meat inspection (MI) code systems. Lung lesions were prioritised as important animal based measures at slaughter, but existing standardized protocols are difficult to implement for routine MI. This study aimed to compare the informative value and feasibility of simplified lung lesion scoring systems to inform future codes for routine post mortem MI. Results Data on lung lesions in finisher pigs were collected at slaughter targeting 83 Irish pig farms, with 201 batches assessed, comprising 31,655 pairs of lungs. Lungs were scored for cranioventral pulmonary consolidations (CVPC) and pleurisy lesions using detailed scoring systems, which were considered the gold standard. Using the data collected, scenarios for possible simplified scoring systems to record CVPC (n = 4) and pleurisy (n = 4) lesions were defined. The measurable outcomes were the prevalence and (if possible) severity scoring at batch level for CVPC and pleurisy. An arbitrary threshold was set to the upper quartile (i.e., the top 25% of batches with high prevalence/severity of CVPC or pleurisy, n = 50). Each pair of measurable outcomes was compared by calculating Spearman rank correlations and assessing if batches above the threshold for one measurable outcome were also above it for their pairwise comparison. All scenarios showed perfect agreement (k = 1) when compared among themselves and the gold standard for the prevalence of CVPC. The agreement among severity outcomes and the gold standard showed moderate to perfect agreement (k = [0.66, 1]). The changes in ranking were negligible for all measurable outcomes of pleurisy for scenarios 1, 2 and 3 when compared with the gold standard (rs ≥ 0.98), but these changes amounted to 50% for scenario 4. Conclusions The best simplified CVPC scoring system is to simply count the number of lung lobes affected excluding the intermediate lobe, which provides the best trade-off between value of information and feasibility, by incorporating information on CVPC prevalence and severity. While for pleurisy evaluation, scenario 3 is recommended. This simplified scoring system provides information on the prevalence of cranial and moderate and severe dorsocaudal pleurisy. Further validation of the scoring systems at slaughter and by private veterinarians and farmers is needed.

Abstract Background Virtual patients provide a safe way to simulate authentic clinical practice. Twine is an open-source software that can be used to create intricate virtual patient games, including elements like non-linear free text history taking and time-related changes to the game’s narrative. We evaluated the incorporation of Twine virtual patient games into a diabetes acute care online learning package for undergraduate medical students at the University of Glassgow, Scotland. Methods Three games were developed using Twine, Wacom Intuous Pro, Autodesk SketchBook, Camtasia Studio, and simulated patients. Online material included three VP games, eight microlectures, and a single best answer multiple choice question quiz. The games were evaluated at Kirkpatrick Level 1 with an acceptability and usability questionnaire. The entire online package was evaluated at Kirkpatrick Level 2 with pre- and post-course multiple choice and confidence questions, with statistical analysis performed using paired t-tests. Results 122 of approximately 270 eligible students provided information on resource utilisation, with 96% of these students using at least one online resource. 68% of students who returned surveys used at least one VP game. 73 students provided feedback on the VP games they had played, with the majority of median responses being “agree” on positive usability and acceptability statements. The online resources were associated with a mean multiple choice score increase from 4.37 out of 10 to 7.96 out of 10 (p

Abstract Background Based on findings primarily using self-report measures, physical activity has been recommended to reduce disability in old age. Collecting objective measures of total daily physical activity in community-dwelling older adults is uncommon, but might enhance the understanding of the relationship of physical activity and disability. We examined whether greater total daily physical activity was associated with less report of disability in the elderly. Methods Data were from the Rush Memory and Aging Project, a longitudinal prospective cohort study of common, age-related, chronic conditions. Total daily physical activity was measured in community-dwelling participants with an average age of 82 using actigraphy for approximately 9 days. Disability was measured via self-reported basic activities of daily living (ADL). The odds ratio and 95% Confidence Interval (CI) were determined for the baseline association of total daily physical activity and ADL disability using a logistic regression model adjusted for age, education level, gender and self-report physical activity. In participants without initial report of ADL disability, the hazard ratio and 95% CI were determined for the relationship of baseline total daily physical activity and the development of ADL disability using a discrete time Cox proportional hazard model adjusted for demographics and self-report physical activity. Results In 870 participants, the mean total daily physical activity was 2. 9 × 105 counts/day (range in 105 counts/day = 0.16, 13. 6) and the mean hours/week of self-reported physical activity was 3.2 (SD = 3.6). At baseline, 718 (82.5%) participants reported being independent in all ADLs. At baseline, total daily physical activity was protective against disability (OR per 105 counts/day difference = 0.55; 95% CI = 0.47, 0.65). Of the participants without baseline disability, 584 were followed for 3.4 years on average. Each 105 counts/day additional total daily physical activity was associated with reduced hazard of developing disability by 25% (HR = 0.75, 95% CI = 0.66, 0.84). The results were unchanged after controlling for important covariates including cognition, depressive symptoms, and chronic health conditions. Conclusions Greater total daily physical activity is independently associated with less disability even after controlling for self-reported physical activity.

Abstract Background The objective of this study was to test the hypothesis that cognitive function is negatively associated with temporal discounting in old age. Methods Participants were 388 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging in the Chicago metropolitan area. Temporal discounting was measured using standard questions in which participants were asked to choose between an immediate, smaller payment and a delayed, larger one. Cognition was measured using a detailed battery including 19 tests. The association between cognition and temporal discounting was examined via mixed models adjusted for age, sex, education, income, and the number of chronic medical conditions. Results Descriptive data revealed a consistent pattern whereby older persons with lower cognitive function were more likely to discount greater but delayed rewards compared to those with higher cognitive function. Further, in a mixed effect model adjusted for age, sex, education, income, and chronic medical conditions, global cognitive function was negatively associated with temporal discounting (estimate = −0.45, SE = 0.18, p = 0.015), such that a person with lower cognition exhibited greater discounting. Finally, in subsequent models examining domain specific associations, perceptual speed and visuospatial abilities were associated with temporal discounting, but episodic memory, semantic memory and working memory were not. Conclusion Among older persons without dementia, a lower level of cognitive function is associated with greater temporal discounting. These findings have implications regarding the ability of older persons to make decisions that involve delayed rewards but maximize well-being.

Abstract Background Recent research has begun to recognize the important influence of literacy levels and how they affect health and wellbeing, especially in older adults. Our study focuses on health and financial literacy, two domains of literacy which previous research has suggested may be significantly related to health and wellbeing. Our study examines the relation of health and financial literacy with health promoting behaviors and health status among community-based older persons. Methods We conducted a cross-sectional study using data from the Rush Memory and Aging Project, a community-based cohort study of aging in northeastern Illinois. The study consisted of 556 older persons without dementia, each determined by a clinical evaluation. Health and financial literacy were measured using a series of questions designed to assess the ability to understand and process health and financial information, concepts, and numeracy; the two scores were averaged to yield a total literacy score. Health promoting behaviors, including engagement in cognitive, physical, and social activities, were assessed using self report measures. Indicators of heath status, including cognition (global cognition and five specific cognitive abilities), functional status (basic and instrumental activities of daily living, mobility disability), and mental health (depressive symptoms, loneliness) were assessed. Results In a series of regression models adjusted for age, sex, and education, higher total literacy scores were associated with more frequent participation in health promoting behaviors, including cognitive, physical and social activities (all p values Conclusions Health and financial literacy are associated with more frequent engagement in health promoting behaviors and better health status in older persons without dementia.

Abstract Background Plant biotechnology can be leveraged to produce food, fuel, medicine, and materials. Standardized methods advocated by the synthetic biology community can accelerate the plant design cycle, ultimately making plant engineering more widely accessible to bioengineers who can contribute diverse creative input to the design process. Results This paper presents work done largely by undergraduate students participating in the 2010 International Genetically Engineered Machines (iGEM) competition. Described here is a framework for engineering the model plant Arabidopsis thaliana with standardized, BioBrick compatible vectors and parts available through the Registry of Standard Biological Parts (http://www.partsregistry.org). This system was used to engineer a proof-of-concept plant that exogenously expresses the taste-inverting protein miraculin. Conclusions Our work is intended to encourage future iGEM teams and other synthetic biologists to use plants as a genetic chassis. Our workflow simplifies the use of standardized parts in plant systems, allowing the construction and expression of heterologous genes in plants within the timeframe allotted for typical iGEM projects.

Abstract Background Emerging data from younger and middle-aged persons suggest that cognitive ability is negatively associated with risk aversion, but this association has not been studied among older persons who are at high risk of experiencing loss of cognitive function. Methods Using data from 369 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the correlates of risk aversion and tested the hypothesis that cognition is negatively associated with risk aversion. Global cognition and five specific cognitive abilities were measured via detailed cognitive testing, and risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing; potential gamble gains ranged from $21.79 to $151.19 with the gain amounts varied randomly over questions. We first examined the bivariate associations of age, education, sex, income and cognition with risk aversion. Next, we examined the associations between cognition and risk aversion via mixed models adjusted for age, sex, education, and income. Finally, we conducted sensitivity analyses to ensure that our results were not driven by persons with preclinical cognitive impairment. Results In bivariate analyses, sex, education, income and global cognition were associated with risk aversion. However, in a mixed effect model, only sex (estimate = -1.49, standard error (SE) = 0.39, p < 0.001) and global cognitive function (estimate = -1.05, standard error (SE) = 0.34, p < 0.003) were significantly inversely associated with risk aversion. Thus, a lower level of global cognitive function and female sex were associated with greater risk aversion. Moreover, performance on four out of the five cognitive domains was negatively related to risk aversion (i.e., semantic memory, episodic memory, working memory, and perceptual speed); performance on visuospatial abilities was not. Conclusion A lower level of cognitive ability and female sex are associated with greater risk aversion in advanced age.

Abstract Background FeFe-hydrogenases are the most active class of H2-producing enzymes known in nature and may have important applications in clean H2 energy production. Many potential uses are currently complicated by a crucial weakness: the active sites of all known FeFe-hydrogenases are irreversibly inactivated by O2. Results We have developed a synthetic metabolic pathway in E. coli that links FeFe-hydrogenase activity to the production of the essential amino acid cysteine. Our design includes a complementary host strain whose endogenous redox pool is insulated from the synthetic metabolic pathway. Host viability on a selective medium requires hydrogenase expression, and moderate O2 levels eliminate growth. This pathway forms the basis for a genetic selection for O2 tolerance. Genetically selected hydrogenases did not show improved stability in O2 and in many cases had lost H2 production activity. The isolated mutations cluster significantly on charged surface residues, suggesting the evolution of binding surfaces that may accelerate hydrogenase electron transfer. Conclusions Rational design can optimize a fully heterologous three-component pathway to provide an essential metabolic flux while remaining insulated from the endogenous redox pool. We have developed a number of convenient in vivo assays to aid in the engineering of synthetic H2 metabolism. Our results also indicate a H2-independent redox activity in three different FeFe-hydrogenases, with implications for the future directed evolution of H2-activating catalysts.

Abstract Background Being alone, as measured by less frequent social interactions, has been reported to be associated with a more rapid rate of motor decline in older persons. We tested the hypothesis that feeling alone is associated with the rate of motor decline in community-dwelling older persons. Methods At baseline, loneliness was assessed with a 5-item scale in 985 persons without dementia participating in the Rush Memory and Aging Project, a longitudinal community-based cohort study. Annual detailed assessment of 9 measures of muscle strength and 9 motor performances were summarized in a composite measure of global motor function. Results Linear mixed-effects models which controlled for age, sex and education, showed that the level of loneliness at baseline was associated with the rate of motor decline (Estimate, -0.016; S.E. 0.006, p = 0.005). For each 1-point higher level of loneliness at baseline, motor decline was 40% more rapid; this effect was similar to the rate of motor decline observed in an average participant 4 years older at baseline. Furthermore, this amount of motor decline per year was associated with about a 50% increased risk of death. When terms for both feeling alone (loneliness) and being alone were considered together in a single model, both were relatively independent predictors of motor decline. The association between loneliness and motor decline persisted even after controlling for depressive symptoms, cognition, physical and cognitive activities, chronic conditions, as well as baseline disability or a history of stroke or Parkinson's disease. Conclusions Among community-dwelling older persons, both feeling alone and being alone are associated with more rapid motor decline, underscoring the importance of psychosocial factors and motor decline in old age.

Abstract Background The engineering of metabolism holds tremendous promise for the production of desirable metabolites, particularly alternative fuels and other highly reduced molecules. Engineering approaches must redirect the transfer of chemical reducing equivalents, preventing these electrons from being lost to general cellular metabolism. This is especially the case for high energy electrons stored in iron-sulfur clusters within proteins, which are readily transferred when two such clusters are brought in close proximity. Iron sulfur proteins therefore require mechanisms to ensure interaction between proper partners, analogous to many signal transduction proteins. While there has been progress in the isolation of engineered metabolic pathways in recent years, the design of insulated electron metabolism circuits in vivo has not been pursued. Results Here we show that a synthetic hydrogen-producing electron transfer circuit in Escherichia coli can be insulated from existing cellular metabolism via multiple approaches, in many cases improving the function of the pathway. Our circuit is composed of heterologously expressed [Fe-Fe]-hydrogenase, ferredoxin, and pyruvate-ferredoxin oxidoreductase (PFOR), allowing the production of hydrogen gas to be coupled to the breakdown of glucose. We show that this synthetic pathway can be insulated through the deletion of competing reactions, rational engineering of protein interaction surfaces, direct protein fusion of interacting partners, and co-localization of pathway components on heterologous protein scaffolds. Conclusions Through the construction and characterization of a synthetic metabolic circuit in vivo, we demonstrate a novel system that allows for predictable engineering of an insulated electron transfer pathway. The development of this system demonstrates working principles for the optimization of engineered pathways for alternative energy production, as well as for understanding how electron transfer between proteins is controlled.

Abstract Background The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. Methods We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. Results After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. Conclusions This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

Abstract Loss of function progranulin (GRN) mutations are a major autosomal dominant cause of frontotemporal dementia (FTD). Patients with FTD due to GRN mutations (FTD-GRN) develop frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A) and exhibit elevated levels of lysosomal proteins and storage material in frontal cortex, perhaps indicating lysosomal dysfunction as a mechanism of disease. To investigate whether patients with sporadic FTLD exhibit similar signs of lysosomal dysfunction, we compared lysosomal protein levels, transcript levels, and storage material in patients with FTD-GRN or sporadic FTLD-TDP type A. We analyzed samples from frontal cortex, a degenerated brain region, and occipital cortex, a relatively spared brain region. In frontal cortex, patients with sporadic FTLD-TDP type A exhibited similar increases in lysosomal protein levels, transcript levels, and storage material as patients with FTD-GRN. In occipital cortex of both patient groups, most lysosomal measures did not differ from controls. Frontal cortex from a transgenic mouse model of TDP-opathy had similar increases in cathepsin D and lysosomal storage material, showing that TDP-opathy and neurodegeneration can drive these changes independently of progranulin. To investigate these changes in additional FTLD subtypes, we analyzed frontal cortical samples from patients with sporadic FTLD-TDP type C or Pick’s disease, an FTLD-tau subtype. All sporadic FTLD groups had similar increases in cathepsin D activity, lysosomal membrane proteins, and storage material as FTD-GRN patients. However, patients with FTLD-TDP type C or Pick’s disease did not have similar increases in lysosomal transcripts as patients with FTD-GRN or sporadic FTLD-TDP type A. Based on these data, accumulation of lysosomal proteins and storage material may be a common aspect of end-stage FTLD. However, the unique changes in gene expression in patients with FTD-GRN or sporadic FTLD-TDP type A may indicate distinct underlying lysosomal changes among FTLD subtypes.

Abstract Background People over the age of 70 carry the greatest burden of chronic disease, disability and health care use. Participation in physical activity is crucial for health, and walking accounts for much of the physical activity undertaken by sedentary individuals. Pedometers are a useful motivational tool to encourage increased walking and they are cheap and easy to use. The aim of this pilot study was to evaluate the feasibility of the use of pedometers plus a theory-based intervention to assist sedentary older women to accumulate increasing amounts of physical activity, mainly through walking. Methods Female participants over the age of 70 were recruited from primary care and randomised to receive either pedometer plus a theory-based intervention or a theory-based intervention alone. The theory-based intervention consisted of motivational techniques, goal-setting, barrier identification and self-monitoring with pedometers and daily diaries. The pedometer group were further randomised to one of three target groups: a 10%, 15% or 20% monthly increase in step count to assess the achievability and acceptability of a range of targets. The primary outcome was change in daily activity levels measured by accelerometry. Secondary outcome measures were lower limb function, health related quality of life, anxiety and depression. Results 54 participants were recruited into the study, with an average age of 76. There were 9 drop outs, 45 completing the study. All participants in the pedometer group found the pedometers easy to use and there was good compliance with diary keeping (96% in the pedometer group and 83% in the theory-based intervention alone group). There was a strong correlation (0.78) between accelerometry and pedometer step counts i.e. indicating that walking was the main physical activity amongst participants. There was a greater increase in activity (accelerometry) amongst those in the 20% target pedometer group compared to the other groups, although not reaching statistical significance (p = 0.192). Conclusion We have demonstrated that it is feasible to use pedometers and provide theory-based advice to community dwelling sedentary older women to increase physical activity levels and a larger study is planned to investigate this further.

Abstract Background Initially developed in the intensive care unit (ICU) at St. Joseph’s Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. Methods From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. Results From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. Conclusions The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Abstract Despite the increased efficiency of sequencing technologies and the development of reduced-representation sequencing (RRS) approaches allowing high-throughput sequencing (HTS) of multiplexed samples, the per-sample genotyping cost remains the most limiting factor in the context of large-scale studies. For example, in the context of genomic selection (GS), breeders need genome-wide markers to predict the breeding value of large cohorts of progenies, requiring the genotyping of thousands candidates. Here, we introduce 3D-GBS, an optimized GBS procedure, to provide an ultra-high-throughput and ultra-low-cost genotyping solution for species with small to medium-sized genome and illustrate its use in soybean. Using a combination of three restriction enzymes (PstI/NsiI/MspI), the portion of the genome that is captured was reduced fourfold (compared to a “standard” ApeKI-based protocol) while reducing the number of markers by only 40%. By better focusing the sequencing effort on limited set of restriction fragments, fourfold more samples can be genotyped at the same minimal depth of coverage. This GBS protocol also resulted in a lower proportion of missing data and provided a more uniform distribution of SNPs across the genome. Moreover, we investigated the optimal number of reads per sample needed to obtain an adequate number of markers for GS and QTL mapping (500–1000 markers per biparental cross). This optimization allows sequencing costs to be decreased by ~ 92% and ~ 86% for GS and QTL mapping studies, respectively, compared to previously published work. Overall, 3D-GBS represents a unique and affordable solution for applications requiring extremely high-throughput genotyping where cost remains the most limiting factor.

Abstract Background One of the most pressing issues in our society is the provision of proper care and treatment for the growing global health challenge of ageing. Assistive Technology and Telecare (ATT) is a key component in facilitation of safer, longer, and independent living for people with dementia (PwD) and has the potential to extend valuable care and support for caregivers globally. The objective of this study was to identify promotors and barriers to implementation and adoption of ATT for PwD and their informal (family and friends) and formal (healthcare professionals) caregivers. Methods Five databases Medline (Ovid), CINAHL, Web of Science, APA PsycINFO and EMBASE were searched. PRISMA guidelines have been used to guide all processes and results. Retrieved studies were qualitative, mixed-method and quantitative, screened using Rayyan and overall quality assessed using Critical Appraisal Skills Programme (CASP) and Mixed Methods Assessment Tool (MMAT). Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria and assigned within categories of high, moderate, or low. NVivo was used for synthesis and analysis of article content. A narrative synthesis combines the study findings. Results Thirty studies (7 quantitative, 19 qualitative and 4 mixed methods) met the inclusion criteria. Identified primary promotors for the implementation and adoption of ATT were: personalized training and co-designed solutions, safety for the PwD, involvement of all relevant stakeholders, ease of use and support, and cultural relevance. Main barriers for the implementation and adoption of ATT included: unintended adverse consequences, timing and disease progress, technology anxiety, system failures, digital divide, and lack of access to or knowledge of available ATT. Conclusion The most crucial elements for the adoption of ATT in the future will be a focus on co-design, improved involvement of relevant stakeholders, and the adaptability (tailoring related to context) of ATT solutions over time (disease process).

Abstract Background Women living with metastatic breast cancer (MBC) are at risk of significantly impaired quality of life (QOL), symptom burden, distress and fear of progression, and unmet needs, yet they face barriers to accessing evidence-based psychosocial treatments. Our group therefore developed Finding My Way-Advanced (FMW-A), a web-based self-guided psychosocial program for women with MBC. This study aims to assess its efficacy in improving mental and other QOL domains, distress, fear of progression, unmet needs, and health service utilisation. Methods The multi-site randomised controlled trial (RCT) will enrol 370 Australian participants. Eligible participants are adult (18 years +) women diagnosed with MBC, with a life expectancy of 6 months or more, with sufficient English-language literacy to provide informed consent. Participants will be identified, screened and referred from one of 10 Australian sites, or via self-referral in response to advertisements. Participants complete four online questionnaires: prior to accessing their program (‘baseline’), 6 weeks later (‘post-intervention’), then 3 months and 6 months post-intervention. Consenting participants will be randomised to either FMW-A (intervention), or Breast Cancer Network Australia’s (BCNA) online/app resource My Journey (minimal intervention attention-control). This is a single-blind study, with randomisation computer-generated and stratified by site. FMW-A is a 6-module program addressing some of the most common issues experienced by women with MBC, with BCNA control resources integrated within the ‘resources’ section. All modules are immediately accessible, with an additional booster module released 10 weeks later. The primary outcome is mental QOL; statistical criteria for superiority is defined as a 4-point difference between groups at post-treatment. Secondary outcomes include other QOL domains, distress, fear of progression, health service use, intervention adherence, and user satisfaction. Discussion This will be the first adequately powered RCT of a self-directed online intervention for women with MBC. If efficacious, FMW-A will help address two national key priorities for management of MBC – enhancing QOL and reducing symptom burden. FMW-A has the potential to address unmet needs and overcome access barriers for this overlooked population, while reducing health system burden. Trial registration The study was registered prospectively with the ANZCTR on 29/10/2021. Trial ID ACTRN12621001482853p. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382714&isReview=true

Abstract Background Rapid magnetic stimulation (RMS) of the phrenic nerves may serve to attenuate diaphragm atrophy during mechanical ventilation. With different coil shapes and stimulation location, inspiratory responses and side-effects may differ. This study aimed to compare the inspiratory and sensory responses of three different RMS-coils either used bilaterally on the neck or on the chest, and to determine if ventilation over 10 min can be achieved without muscle fatigue and coils overheating. Methods Healthy participants underwent bilateral anterior 1-s RMS on the neck (RMSBAMPS) (N = 14) with three different pairs of magnetic coils (parabolic, D-shape, butterfly) at 15, 20, 25 and 30 Hz stimulator-frequency and 20% stimulator-output with + 10% increments. The D-shape coil with individual optimal stimulation settings was then used to ventilate participants (N = 11) for up to 10 min. Anterior RMS on the chest (RMSaMS) (N = 8) was conducted on an optional visit. Airflow was assessed via pneumotach and transdiaphragmatic pressure via oesophageal and gastric balloon catheters. Perception of air hunger, pain, discomfort and paresthesia were measured with a numerical scale. Results Inspiration was induced via RMSBAMPS in 86% of participants with all coils and via RMSaMS in only one participant with the parabolic coil. All coils produced similar inspiratory and sensory responses during RMSBAMPS with the butterfly coil needing higher stimulator-output, which resulted in significantly larger discomfort ratings at maximal inspiratory responses. Ten of 11 participants achieved 10 min of ventilation without decreases in minute ventilation (15.7 ± 4.6 L/min). Conclusions RMSBAMPS was more effective than RMSaMS, and could temporarily ventilate humans seemingly without development of muscular fatigue. Trial registration This study was registered on clinicaltrials.gov (NCT04176744).

Abstract Background The COVID-19 pandemic has significantly impacted the delivery of diabetes in pregnancy care and general maternity care. This study aimed to explore the experiences and acceptability of telehealth use in diabetes in pregnancy care during the COVID-19 pandemic, from the perspectives of pregnant women and their clinicians. The secondary aim was to explore the experiences of pregnant women receiving general maternity care via telehealth during the COVID-19 pandemic. Methods In-depth qualitative semi-structured interviews were undertaken and analysed via thematic inductive approaches. The Nonadoption, Abandonment, and Challenges to the Scale-Up, Spread, and Sustainability of Health and Care Technologies Framework (NASSS) was applied. Results Eigthteen interviews were conducted with culturally and linguistically diverse pregnant women and 4 clinicians (endocrinologists and dietitians). All interviewees were satisfied with telehealth as a positive alternative to face-to-face consultations for diabetes care during the COVID-19 pandemic. Numerous benefits of delivering diabetes care via telehealth were discussed and themes centred around greater access to care, economic benefits and improved safety. Most barriers concerned the adopters (clinicians), yet, feasible and realistic suggestions to overcome barriers were voiced. The scope for technology adaptation and ongoing embedment into routine diabetes care was described. Overall, a hybrid flexible delivery model, predominantly consisting of telephone consultations, with some face-to-face consultations for initial diabetes appointments was recommended for future care. The use of telehealth in replacement of face-to-face appointments for general maternity care was perceived as reducing care quality. Conclusion In this study, telehealth was viewed as acceptable to women and clinicians for diabetes in pregnancy care, supporting the ongoing delivery of a hybrid service model of telehealth and face-to-face care. These findings provide valuable information to improve diabetes in pregnancy services to meet the needs of women during the COVID-19 pandemic and beyond.

Abstract Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer’s disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASO SNCA could be therapeutic in a mouse model of AD. The efficacy of the ASO SNCA was measured via immunocytochemistry, RT-qPCR and western blotting. To assess spatial learning and memory, ASO SNCA or PBS-injected APP and non-transgenic (NTG) mice, and separate groups of SNCA-null mice, were tested on the Barnes circular maze. Hippocampal slice electrophysiology and transcriptomic profiling were used to explore synaptic function and differential gene expression between groups. Reduction of SNCA transcripts alleviated cognitive deficits in male transgenic animals, but surprisingly, not in females. To determine the functional cause of this differential effect, we assessed memory function in SNCA-null mice. Learning and memory were intact in male mice but impaired in female animals, revealing that the role of αSyn on cognitive function is sex-specific. Transcriptional analyses identified a differentially expressed gene network centered around EGR1, a central modulator of learning and memory, in the hippocampi of SNCA-null mice. Thus, these novel results demonstrate that the function of αSyn on memory differs between male and female brains.