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Despite consensus guidelines, most patients with early-stage triple-negative (TN) and HER2-positive (HER2+) breast cancer do not see a medical oncologist prior to surgery and do not receive neoadjuvant chemotherapy (NAC). To understand barriers to care, we aimed to characterize the relationship between geography (region of residence and cancer centre proximity) and receipt of a pre-treatment medical oncology consultation and NAC for patients with TN and HER2+ breast cancer. Using linked administrative datasets in Ontario, Canada, we performed a retrospective population-based analysis of women diagnosed with stage I–III TN or HER2+ breast cancer from 2012 to 2020. The outcomes were a pre-treatment medical oncology consultation and the initiation of NAC. We created choropleth maps to assess the distribution of the outcomes and cancer centres across census divisions. To assess the relationship between distance to the nearest cancer centre and outcomes, we performed multivariable regression analyses adjusted for relevant factors, including tumour extent and nodal status. Of 14,647 patients, 29.9% received a pre-treatment medical oncology consultation and 77.7% received NAC. Mapping demonstrated high interregional variability, ranging across census divisions from 12.5% to 64.3% for medical oncology consultation and from 8.8% to 64.3% for NAC. In the full cohort, compared to a distance of ≤5 km from the nearest cancer centre, only 10–25 km was significantly associated with lower odds of NAC (OR 0.83, 95% CI 0.70–0.99). Greater distances were not associated with pre-treatment medical oncology consultation. The interregional variability in medical oncology consultation and NAC for patients with TN and HER2+ breast cancer suggests that regional and/or provider practice patterns underlie discrepancies in the referral for and receipt of NAC. These findings can inform interventions to improve equitable access to NAC for eligible patients.

The COVID-19 pandemic has precipitated profound global transformations, and in the Philippines, Emergency Remote Learning (ERT) emerged as a vital response to address the educational needs of students during this crisis. While existing research has extensively examined the challenges faced by parents during ERT, limited attention was devoted to understanding the unique experiences of parents of children with intellectual disabilities (ID) and hearing impairments (HI). Using a qualitative descriptive case study within interpretative paradigm, this study aims to fill this gap by exploring the challenges encountered and coping strategies employed by 15 parents in the Philippines who have children with ID and HI. Findings illuminate the multifaceted challenges faced by parents, encompassing their roles as caregivers and facilitators of their children’s education. Moreover, it reveals the support mechanisms available to these parents, while also highlighting the pressing need for additional assistance to better meet the complex needs of these children. The research also identifies the most effective strategies employed by parents to navigate the challenges of remote learning. The results serve as a critical resource for parents, educators, and policymakers, providing a roadmap for enhancing the support system for families with children who have ID and HI, particularly during times of crisis.

Abstract Background Sleep apnea syndrome, characterized by recurrent cessation (apnea) or reduction (hypopnea) of breathing during sleep, is a major risk factor for postoperative respiratory depression. Challenges in sleep apnea assessment have led to the proposal of alternative metrics derived from oxyhemoglobin saturation (SpO2), such as oxygen desaturation index (ODI) and percentage of cumulative sleep time spent with SpO2 below 90% (CT90), as predictors of postoperative respiratory depression. However, their performance has been limited with area under the curve of 0.60 for ODI and 0.59 for CT90. Our objective was to propose novel features from preoperative overnight SpO2 which are correlated with sleep apnea severity and predictive of postoperative respiratory depression. Methods Preoperative SpO2 signals from 235 surgical patients were retrospectively analyzed to derive seven features to characterize the sleep apnea severity. The features included entropy and standard deviation of SpO2 signal; below average burden characterizing the area under the average SpO2; average, standard deviation, and entropy of desaturation burdens; and overall nocturnal desaturation burden. The association between the extracted features and sleep apnea severity was assessed using Pearson correlation analysis. Logistic regression was employed to evaluate the predictive performance of the features in identifying postoperative respiratory depression. Results Our findings indicated a similar performance of the proposed features to the conventional apnea–hypopnea index (AHI) for assessing sleep apnea severity, with average area under the curve ranging from 0.77 to 0.81. Notably, entropy and standard deviation of overnight SpO2 signal and below average burden showed comparable predictive capability to AHI but with minimal computational requirements and individuals’ burden, making them promising for screening purposes. Our sex-based analysis revealed that compared to entropy and standard deviation, below average burden exhibited higher sensitivity in detecting respiratory depression in women than men. Conclusion This study underscores the potential of preoperative SpO2 features as alternative metrics to AHI in predicting postoperative respiratory.

Abstract Background Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. Methods Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. Results Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. Conclusion Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients’ and recruiters’ experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups.

Abstract Although patients experiencing food insecurity commonly screen positive for a myriad of social determinants of health (SDOH) needs and chronic medical conditions influenced by diet, few studies have investigated associations within both uninsured and food insecure populations. We screened patients for food insecurity using the USDA six-item short form between October 2021 and April 2022. We then evaluated associations of food security status with nine separate SDOH needs and eight chronic medical conditions. In this cross-sectional study, of the 190 patients seen at a student-run free clinic serving patients without health insurance, 135 (71%) completed the SDOH survey. We identified chronic medical conditions via retrospective chart review and analyzed associations using multivariable logistic regressions adjusted for age and sex. Uninsured participants experiencing food insecurity (n = 22,16.3%) requested more support for: medications (adjusted odds ratio [AOR] = 7.28; 95% Confidence Interval [95% CI] = 2.33–23.2); p-value [P] =

Objective:. The objective of this study was to measure potential associations between surgeon sex and number of days alive and at home (DAH). Background:. Patients treated by female surgeons appear to have lower rates of mortality, complications, readmissions, and healthcare costs when compared with male surgeons. DAH is a validated measure, shown to better capture the patient experience of postoperative recovery. Methods:. We conducted a retrospective study of adults (≥18 years of age) undergoing common surgeries between January 01, 2007 and December 31, 2019 in Ontario, Canada. The outcome measures were the number of DAH within 30-, 90-, and 365-days. The data was summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results:. During the study period, 1,165,711 individuals were included, of which 61.9% (N = 721,575) were female. Those managed by a female surgeon experienced a higher mean number of DAH when compared with male surgeons at 365 days (351.7 vs. 342.1 days; P < 0.001) and at each earlier time point. This remained consistent following adjustment for covariates, with patients of female surgeons experiencing a higher number of DAH at all time points, including at 365 days (343.2 [339.5–347.1] vs. 339.4 [335.9–343.0] days). Multivariable regression modeling revealed that patients of male surgeons had a significantly lower number of DAH versus female surgeons. Conclusions:. Patients of female surgeons experienced a higher number of DAH when compared with those treated by male surgeons at all time points. More time spent at home after surgery may in turn lower costs of care, resource utilization, and potentially improve quality of life. Further studies are needed to examine these findings across other care contexts.

Safe drinking water availability is a concern in Haiti. Public systems have limited coverage and reliability. Private wells and local water sources are often of unknown or poor quality. Public health events, such as the 2010 cholera outbreak, demonstrate vulnerability to water contamination. To address these concerns, a drinking water laboratory was established at the Campus Henri Christophe in Limonade, a branch of the State University of Haiti, to meet water testing demands from local clients such as for-profit kiosks, institutions, industries, and municipal water systems. This study assessed the financial viability of a university-based drinking water laboratory in Haiti by calculating Internal Rate of Return and Net Present Value. Sensitivity analysis was used to identify the range of conditions under which laboratory revenues would cover operating costs. To achieve an acceptable profitability level, the laboratory must perform microbiological testing for routine monitoring samples and test an average of five samples per day. Price-based incentives for new clients have relatively small impacts on profitability. Finally, international and Haitian inflation cause some variation in profitability. These economic factors will be among the key drivers of laboratory operation costs. The results underscore the main factors that must be considered to make the laboratory successful and the importance of strategic marketing for laboratory managers to encourage clients to regularly test drinking water and emphasize microbiological testing.

Objective and Approach To address the opioid crisis within the Red River Métis (RRM) Community, understanding opioid use is crucial to empower regional health authorities to adapt health programs, services, and policies to meet their unique needs effectively. The investigation utilized focus groups with a Community-Based Participatory Research and Collective Consensual Data Analytics Procedure (CBPR/CCDAP) approach. Additionally, a population-based retrospective cross-sectional study for fiscal years 2006/07–2018/19 was conducted using administrative data from a population research data repository. Rates of prescription opioid dispensing (RPOD) and mean morphine equivalents (MEQ) were compared between RRM and all other Manitobans (AOM) aged 10 years or older. Results The rate of prescription opioid dispensing and MEQ/person were found to be consistently higher among RRM compared to AOM in each study year (p < 0.001). While the RPOD declined among AOM over the study period, it did not change among RRM. Key findings revealed RRM were concerned about how opioids impacted their communities, and felt the need for increased addiction treatment resources, including Red River Métis culture-specific programs. Conclusion The evidence demonstrates higher RPOD and MEQ among RRM compared to AOM, suggesting elevated risk of opioid-related harms. Focus group feedback reinforces the need for tailored interventions. Implications Future policies and programs targeting the opioid crisis should prioritize the unique needs of populations like the RRM, requiring tailored, culturally appropriate interventions for effective crisis management.

Objective and Approach The study investigates attitudes of Red River Métis (RRM) Citizens towards existing mental health services to assess satisfaction levels and enhance support and accessibility. Employing a Community-Based Participatory Research and Collective Consensual Data Analytic Procedure (CBPR/CCDAP) framework, a survey was conducted during health consultations in 2022 and 2023. It explored participant perspectives on existing programming, service availability, and future needs. Analysis of participant responses, stratified by demographics, offers insights into mental health attitudes among the RRM Community. Results A total of 144 RRM Citizens participated in the survey, reporting "addiction," "trauma," and "stress" as primary causes of mental health issues. Presently, only 20% (n = 29) utilize mental health services, with over 40% (n = 58) expressing dissatisfaction with available services. Moreover, more than 90% (n = 130) of Citizens emphasized “an urgent need for additional mental health services tailored to the RRM Community”. Common barriers to accessing mental health services included lack of awareness and financial constraints. Conclusion The study highlights RRM Citizens’ dissatisfaction with existing services and inadequate awareness of available mental health services and their protocols, presenting significant barriers to accessing services. Further investigations are warranted to determine whether these challenges stem from communication discrepancies, service inadequacies, or a combination of both factors. Implications Findings from the study inform the development of distinctions-based mental health services for the Red River Métis Community, enhancing access, engagement, and policy development to address mental health disparities.

Abstract Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 participants in the International COVID Sleep Study-II (ICOSS-II) were used. Method-Self and Method-MCTQ were compared. Method-Self involved a single question about average nightly sleep duration (HSDself), while Method-MCTQ estimated HSD from reported sleep times on workdays (HSDMCTQwork) and free days (HSDMCTQfree). Sleep quality was evaluated using a Likert scale and the Insomnia Severity Index (ISI) to explore its influence on estimation bias. HSDself was on average 42.41 ± 67.42 min lower than HSDMCTQweek, with an agreement range within ± 133 min. The bias and agreement range between methods increased with poorer SQ. HSDMCTQwork showed less bias and better agreement with HSDself compared to HSDMCTQfree. Sleep duration irregularity was − 43.35 ± 78.26 min on average. Subjective sleep quality predicted a significant proportion of variance in HSDself and estimation bias. The two methods showed very poor agreement and a significant systematic bias, both worsening with poorer SQ. Method-MCTQ considered sleep intervals without adjusting for SQ issues such as wakefulness after sleep onset but accounted for sleep irregularity and sleeping in on free days, while Method-Self reflected respondents’ interpretation of their sleep, focusing on their sleep on workdays. Including an SQ-related question in surveys may help bidirectionally adjust the possible bias and enhance the accuracy of sleep-health studies.

Abstract Background Dentists serve a crucial role in managing treatment complications for patients with head and neck cancer, including post-radiation caries and oral infection. To date, dental services for head and neck cancer patients in Ontario, Canada have not been well characterized and considerable disparities in allocation, availability, and funding are thought to exist. The current study aims to describe and assess the provision of dental services for head and neck cancer patients in Ontario. Methods A mixed methods scoping assessment was conducted. A purposive sample of dentist-in-chiefs at each of Ontario’s 9 designated head and neck cancer centres (tertiary centres which meet provincially-set quality and safety standards) was invited to participate. Participants completed a 36-item online survey and 60-minute semi-structured interview which explored perceptions of dental services for head and neck cancer patients at their respective centres, including strengths, gaps, and inequities. If a centre did not have a dentist-in-chief, an alternative stakeholder who was knowledgeable on that centre’s dental services participated instead. Thematic analysis of the interview data was completed using a mixed deductive-inductive approach. Results Survey questionnaires were completed at 7 of 9 designated centres. A publicly funded dental clinic was present at 5 centres, but only 2 centres provided automatic dental assessment for all patients. Survey data from 2 centres were not captured due to these centres’ lack of active dental services. Qualitative interviews were conducted at 9 of 9 designated centres and elicited 3 themes: (1) lack of financial resources; (2) heterogeneity in dentistry care provision; and (3) gaps in the continuity of care. Participants noted concerning under-resourcing and limitations/restrictions in funding for dental services across Ontario, resulting in worse health outcomes for vulnerable patients. Extensive advocacy efforts by champions of dental services who have sought to mitigate current disparities in dentistry care were also described. Conclusions Inequities exist in the provision of dental services for head and neck cancer patients in Ontario. Data from the current study will broaden the foundation for evidence-based decision-making on the allocation and funding of dental services by government health care agencies.

There is a 17-year gap between the publication of research which proves an intervention is efficacious and effective and the implementation of that same intervention into practice [1]. In behavioral health, only 14% of successful interventions are integrated into actual practice [2]. As such, Implementation Science is envisioned to address the research to practice gap. This research methodology becomes important as it looks to investigate how to get interventions to become embedded in practice and de-implement unproven or disproven interventions that may be harmful and/or ineffective for patients. The aim of this commentary is to raise awareness of health sciences librarians/information specialists about this research arena and encourage health sciences librarians to envision how they could be involved in implementation science projects and teams or even use implementation science in their practice.

Background Functional neurological disorder (FND) is a heterogeneous condition; severe forms can be disabling. Multidisciplinary treatment and rehabilitation are recommended for severe FND, but there remains a lack of evidence for its efficacy and lack of understanding of the predictors and components of recovery.Methods We report clinical outcome data for an inpatient cohort with severe FND. Clinical Global Impression Improvement with treatment is the primary outcome measure. Admission and discharge measures (Euroqol quality of life measures, Beck Depression Inventory, Spielberger Trait Anxiety Inventory, Cambridge Depersonalisation Scale, Illness Perception Questionnaire (Revised) and Functional Mobility Scale) are reported as secondary outcomes.Results We describe an FND cohort (n=52) with chronic illness (mean symptom duration 9.7 years). At admission, there were clinically relevant levels of depression, anxiety and depersonalisation derealisation. At the time of discharge, most (43/52) patients’ global condition had improved. Measures of mobility, depression and quality of life also significantly improved while at discharge, symptoms were experienced as more understandable and less distressing than at admission. An admission measure of patient confidence in treatment was predictive of eventual clinical outcome.Conclusions The most frequent outcome of inpatient rehabilitation is global improvement, even when symptoms are chronic and severe, reflected in measurable changes in both physical and psychological functioning. Significant levels of depersonalisation derealisation seen in this patient group suggest that routine enquiry into such experiences could help personalise FND treatment approaches. Patient confidence in treatment is key in determining clinical outcomes.

Segmental arterial mediolysis (SAM) is a rare, noninflammatory, nonatherosclerotic condition that occurs commonly in mesenteric vessels. There are no known predisposing risk factors to the development of SAM. We present a case of a 67-year-old woman who presented with abdominal pain 2 days following discharge after an elective endovascular abdominal aortic intervention. Repeat imaging 2 days after readmission showed the presence of multiple new aneurysms involving the mesenteric vasculature. She underwent attempted endovascular embolization of the largest aneurysm. The postmortem and histopathologic examinations confirmed the diagnosis of SAM.

Autism is a developmental condition that affects motor skill development. There is a lack of comprehensive research exploring the potential benefits of extended reality (XR) technologies, including virtual reality (VR) and augmented reality (AR), for improving motor skills in autistic children. This systematic literature review (SLR) addresses this research gap by investigating XR-based interventions targeting motor skill development in autistic children. The SLR analysed 15 primary studies published between 2012 and 2024, examining the use of VR and AR to improve motor skill development in autistic children. The interventions ranged from one session to 12 weeks, lasting 12 to 45 minutes, and targeted various body movements. XR platforms and devices used included VR headsets, motion capture systems, and exercise bikes. Recurrent neural networks, dynamic difficulty adjustment, and behaviour trees were employed to enhance intervention dynamics and extract valuable insights from collected data. The results suggest that using XR interventions has significant potential to improve physical activity levels and motor skills development among autistic children. However, the research designs varied, with only one study including their intervention framework’s generalisation and maintenance phases. This study offers an encouraging avenue for future research and intervention design in this field.

Abstract Background Despite that stakeholder participation in evidence synthesis could result in more useful outcomes, there are few examples of processes that actively involve them in synthesis work. Techniques are needed that engage diverse stakeholders as equal partners in knowledge co-production. The aims of this paper are to describe an innovative participatory process of synthesising a large body of academic research products and compare the findings of the participatory process against two traditional approaches to synthesis: a rapid review and a structured review. Methods First, a rapid synthesis of all research outputs (n = 86) was conducted by researchers with in-depth knowledge of the collaboration’s research. Second, a team of researchers and service providers conducted a structured synthesis of seventy-eight peer-reviewed articles and reports generated by the collaboration. Fifty-five publications were brought forward for further synthesis in part three, a facilitated participatory synthesis. Finally, we explored the value added by the participatory method by comparing findings generated across the three synthesis approaches. Results Twelve researchers and 11 service providers/policy partners—8 self-identified as Aboriginal and/or Torres Strait Islander—participated in two facilitated workshops (totalling 4 h). Workshop activities engaged participants in reviewing publication summaries, identifying key findings, and evoked review, discussion and refinement. The process explicitly linked experiential knowledge to citations of academic research, clearly connecting the two knowledge types. In comparing the findings generated across all three methods we found mostly consistencies; the few discrepancies did not contradict but gave deeper insights into statements created by the other methods. The participatory synthesis generated the most, detailed, and unique findings, and contextual insights about the relevance of the key messages for practice. Conclusion The participatory synthesis engaged stakeholders with diverse backgrounds and skillsets in synthesising a large body of evidence in a relatively short time. The participatory approach produced findings comparable to traditional synthesis methods while extending knowledge and identifying lessons most relevant for the participants who, ultimately, are the end users of the research. This process will interest other large-scale research collaborations seeking to engage stakeholders in evidence synthesis.

Sports organizations are complex. In addition to the actual coaching of athletes, many utilize a myriad of different administrative and sport science departments or areas of expertise to aid in the achievement of success. Examples include sports administration, nutrition, strength and conditioning, sport psychology, counseling, athletic training, to name a few. Consequently, there are many voices within the organization, and communication and effectiveness may be affected by silos, fear of voicing opinions, or other chal¬lenges that come from the stresses and rigors of athletic competition. Anecdotally, we have noticed the often-informal introduction of an individual into some sports organizations and teams to help support the overall organization and its personnel. This individual does not necessarily have decision-making pow¬ers, but serves as a conduit of information, a supporter, and an advisor to all parties. To date, a specific title for this position has not been formally recognized, nor have its roles or responsibilities been defined. There¬fore, the purpose of this conceptual article is to propose a name for this position, which we have termed Athletic Consul (AC). Further, we outline why such a position is valuable, its fit within an athletic program, the roles and responsibilities of the position, and why it is necessary for such this position be formalized.

Abstract Background Red River Métis families need access to meaningful and appropriate resources when their children are sick. At the invitation of the Manitoba Métis Federation (MMF) to partner in this research, our aim was to understand Red River Métis parents’ experiences and preferences for seeking child health information when their child is acutely ill, to inform the adaptation of existing parent resources. Methods A qualitative descriptive approach underpinned by a participatory paradigm guided this study. Semi-structured interviews were conducted with 19 Red River Métis parents and Elders via Zoom or telephone. An inductive thematic analysis approach was used to explore patterns and themes across the data. Results Analysis generated four themes: (1) We’re here too; (2) We are not all the same; (3) Finding trustworthy information; and (4) Information needs to be widely available. Red River Métis pride was prominent in the results. Parents provided tangible ways to modify existing parent resources, including adding information on how to access Elders, healers and/or traditional medicines and showing different family structures, transport, living situations, Métis names, and incorporating Métis languages. While most parents reported looking for child health information online, they also stressed the need to provide multiple options, including information sheets, recognizing that parents seek information in different contexts. Parents also emphasized the importance of accessible, safe spaces to find child health information, including local schools, community centres, healthcare organizations and the MMF. Conclusion There is a lack of child health information created specifically for Red River Métis families. The development of this information can support their information needs and preferences and the ongoing efforts to revitalize Red River Métis culture and language. Study findings will inform the adaptation and dissemination of existing child health resources to ensure they reflect Red River Métis parents’ information needs and preferences. This research is a critical step in addressing an identified need for Red River Métis families to have culturally relevant and meaningful child health resources, and in the pursuit of equitable care for all children in Canada. Trial Registration N/A.

Abstract Background Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. Methods Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. Results Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (β = −0.056 and −0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). Conclusions Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets?the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20?1.51?kg; 6?9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n?=?4), a 22J (joules) impact (n?=?4), or a 27J impact (n?=?4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24?h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.

Abstract Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.

Efforts to measure and regulate groundwaters and irrigators are notoriously ineffective. The starting point of this article, therefore, is to question the continued faith in techno-managerial solutions to groundwater depletion. We discuss the potential of the conceptual vocabulary of ‘care’ to complement, refresh and expand ways of talking about and doing groundwater governance. Mobilizing a diverse range of examples from places where pressures on aquifers are particularly acute, we do this by exploring what care entails in everyday practices of groundwater use and management. We show that foregrounding care nuances and sometimes challenges stories of users unavoidably depleting aquifers when given the chance and means to do so. Irrigators may display concern about the longer-term sustainability of the aquifers on which their livelihoods depend, even when their own pumping practices are unsustainable. In spite of pressures to intensify and individualize, farmers sometimes do hold on to or creatively develop collective rules to fairly share groundwater and use it sustainably, complementing strategies to make do with what is available with investments in conservation and recharge. Attention to care, moreover, highlights the ongoing processes of tinkering that governing groundwater always entails. The ability to tinker hinges on intimate and often embodied knowledge of a watery place. Accepting the care involved in governing groundwater, our analysis therefore concludes, prompts a re-consideration of what is and who has water expertise, with important implications for the role of ‘outside’ experts. More than a new theory, we propose embracing care as an analytical sensibility, with the study of practices of care serving as one promising way to widen the conceptual and political space for understanding and doing human-groundwater relations.

BackgroundIn patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy.MethodsThe phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination.ResultsBetween June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation.ConclusionThe study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study.Clinical trial registrationclinicaltrials.gov, ID NCT04050228.

Abstract Background The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets. Methods LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry. Results Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n‐fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; −8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF. Conclusions DDD involves a significant upregulation of various TNFSF members, with tissue‐specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.

Abstract Background Shortness of breath occurs in 10%–70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients' severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. Methods Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests. Results For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer‐specific stress. Conclusions Clinicians can use the information provided in this study to identify high‐risk patients and develop individualized interventions.

**Background:** The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. **Methods:** A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. **Results:** Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. **Conclusion:** This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

Abstract Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

Abstract Background Movement behaviours (physical activity, sedentary behaviour, and sleep) are important for pre-school children’s health and development. Currently, no tools with appropriate content validity exist that concurrently capture these movement behaviours in young children. The aim of this study was to co-design and assess the content validity of a novel tool to concurrently measure movement behaviours in pre-school aged children (aged 3–4 years). Methods We followed four distinct steps to develop and assess the content validity of Movement Measurement in the Early Years (MoveMEY): (1) We conducted an extensive literature search, to identify pre-existing proxy measurement tools (questionnaires and diaries) to inform the design of a novel tool, which aimed to effectively capture movement behaviour guidelines of pre-school aged children. (2) We facilitated focus group discussions with parents and carers of pre-school aged children (n = 11) and (3) a qualitative survey with free text responses was completed by topic relevant researchers (n = 6), to co-design the measurement tool. (4) We assessed the content validity of the developed tool, MoveMEY, through interviews with parents of pre-school aged children (n = 12) following piloting of the tool. Results We developed an initial version of MoveMEY based on the format of an existing questionnaire and by mapping the content of questions to the guidelines. Co-design of MoveMEY resulted in changes to the format (e.g. short questionnaire to a seven-day diary) and content (e.g. inclusion of ‘general information’ questions on illness, disabilities and sleep disturbances; question on screen time before bed). Content validity assessment demonstrated that the items of MoveMEY were relevant and comprehensive for the assessment of children’s movement behaviours. MoveMEY was felt to be comprehensible, however, parental suggestions were implemented to finalise and improve MoveMEY (e.g. adding examples to questions aiming to detect moderate to vigorous physical activity). Conclusion MoveMEY is the first co-designed measurement tool that has relevance for assessing the movement behaviour guidelines of pre-school aged children. Parent/carer and topic relevant researcher involvement throughout the development process resulted in a seven-day daily reported activity diary that is comprehensive of children’s movement behaviours and comprehensible to parents and carers.

Historically, water utilities have relied on tried-and-true practices in the design and operation of their infrastructure, tapping new resources and expanding networks as needed. However, as the effects of climate change and/or urbanization increasingly impact both water supply and demand, utilities need new, holistic planning and management approaches. Integrated planning approaches must account for changing policies, technological progress, and unique, setting-specific operating conditions. Based on this notion, an international web seminar with faculty, researchers, and students from nine universities across five continents was conducted. In the 3-month seminar, participants were split into groups and tasked with developing future-proof, sustainable water management solutions for fictitious settings with unique resource availability, climate change predictions, demographic, and socioeconomic constraints. The goal of the seminar was to combine participants’ unique perspectives to tackle challenges in developing future water infrastructure, while forming lasting relationships. Water management concepts became more daring or “out-of-the-box” as the seminar progressed. Most groups opted for a holistic approach, optimizing existing infrastructure, integrating decentralized water management, furthering digitization, and fostering the adoption of innovative policy and planning strategies. To gauge their impact on the evolution of ideas, group dynamics and communication were observed throughout the seminar. As a result, the findings serve not only as a compendium of ideas and concepts for holistic design in the water sector, but also facilitate international collaboration, improve communication in cross-cultural teams or guide the development of training programs in water management for researchers, professional engineers, or water utilities.

Unprecedented plastic production has resulted in over six billion tons of harmful waste. Certain insect taxa emerge as potential agents of plastic biodegradation. Through a comprehensive manual and bibliometric literature analysis, this review analyses and consolidates the growing literature related to insect-mediated plastic breakdown. Over 23 insect species, representing Coleoptera, Lepidoptera, and 4 other orders, have been identified for their capacity to consume plastic polymers. Natural and synthetic polymers exhibit high-level similarities in molecular structure and properties. Thus, in conjunction with comparative genomics studies, we link plastic-degrading enzymatic capabilities observed in certain insects to the exaptation of endogenous enzymes originally evolved for digesting lignin, cellulose, beeswax, keratin and chitin from their native dietary substrates. Further clarification is necessary to distinguish mineralisation from physicochemical fragmentation and to differentiate microbiome-mediated degradation from direct enzymatic reactions by insects. A bibliometric analysis of the exponentially growing body of literature showed that leading research is emerging from China and the USA. Analogies between natural and synthetic polymer’s degradation pathways will inform engineering robust enzymes for practical plastic bioremediation applications. By aggregating, analysing, and interpreting published insights, this review consolidates our mechanistic understanding of insects as a potential natural solution to the escalating plastic waste crisis.

Abstract Background The severity of sleep-disordered breathing is known to worsen postoperatively and is associated with increased cardio-pulmonary complications and increased resource implications. In the general population, the semi-upright position has been used in the management of OSA. We hypothesized that the use of a semi-upright position versus a non-elevated position will reduce postoperative worsening of OSA in patients undergoing non-cardiac surgeries. Methods This study was conducted as a prospective randomized controlled trial of perioperative patients, undergoing elective non-cardiac inpatient surgeries. Patients underwent a preoperative sleep study using a portable polysomnography device. Patients with OSA (apnea hypopnea index (AHI) > 5 events/hr), underwent a sleep study on postoperative night 2 (N2) after being randomized into an intervention group (Group I): semi-upright position (30 to 45 degrees incline), or a control group (Group C) (zero degrees from horizontal). The primary outcome was postoperative AHI on N2. The secondary outcomes were obstructive apnea index (OAI), central apnea index (CAI), hypopnea index (HI), obstructive apnea hypopnea index (OAHI) and oxygenation parameters. Results Thirty-five patients were included. Twenty-one patients were assigned to the Group 1 (females-14 (67%); mean age 65 ± 12) while there were fourteen patients in the Group C (females-5 (36%); mean age 63 ± 10). The semi-upright position resulted in a significant reduction in OAI in the intervention arm (Group C vs Group I postop AHI: 16.6 ± 19.0 vs 8.6 ± 11.2 events/hr; overall p = 0.01), but there were no significant differences in the overall AHI or other parameters between the two groups. Subgroup analysis of patients with “supine related OSA” revealed a decreasing trend in postoperative AHI with semi-upright position, but the sample size was too small to evaluate statistical significance. Conclusion In patients with newly diagnosed OSA, the semi-upright position resulted in improvement in obstructive apneas, but not the overall AHI. Trial registration This trial was retrospectively registered in clinicaltrials.gov NCT02152202 on 02/06/2014.

Abstract This study aimed to examine the difference in therapy satisfaction between lesbian, gay, and bisexual + (LGB +) individuals and heterosexual individuals, and to identify the association between therapy satisfaction and the perception of knowledge and attitudes of their last therapist among the LGB + participants. Through an exploratory design with a comparative group, 125 LGB + and 75 heterosexual participants were recruited online by availability. Results indicate that the participants’ sexual orientation has no significant relation on therapy satisfaction. However, there was a significant positive association between satisfaction with therapy and the LGB + participants’ perception that their therapist demonstrated knowledge and positive attitudes. This research highlights the importance for continuous education and curriculum efforts on LGB + issues.

IntroductionDepression is one of the most common yet underdiagnosed perinatal complications and our understanding of its pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants (e.g., biological, behavioral, environmental, social) and interactions among determinants of perinatal depression and the quality of methods applied.MethodsFour databases (i.e., PubMed, CINAHL, APA PsycInfo, Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, depression was examined in a specific subpopulation evidenced to have psychological consequences due to situational stressors (e.g., fetal/infant loss, neonatal intensive care unit admission), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias.ResultsOf the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 32% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias.ConclusionsFuture research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.

Oil palm plantations growing on peat soil are associated with high soil CO2 emissions. Oil palm plantations are set up with regular spatial patterns consisting of different surface management microforms: bare soil harvest paths, frond piles, cover plants and drainage ditches. Currently, there is limited understanding about the extent that this spatial variation impacts soil carbon losses, in part due to the challenges of partitioning peat oxidation from total soil respiration. We explored this spatial variation by measuring total soil respiration (Rtot), root density and environmental variables at 210 locations. Measurements were taken along transects going from the base of oil palms into the different microforms. Rtot was partitioned into root respiration (Ra) and heterotrophic respiration (Rh) using two different methods: (i) a “distance from palm” method (which utilizes the fluxes taken from soil with minimal root density) and (ii) a “linear regression” method (which models root density and Rtot, using the regression intercept for Rh). Here, the distance from palm partitioning method gave higher Rh estimates than the linear regression method. Rh varied significantly between the different palms used in the assessment but did not show significant spatial variation aside from this. Rtot and Ra were highest next to the palm and decreased with increasing distance from the palm. Rtot and Ra also showed significant spatial variation between the different surface management microforms, with each giving significantly higher fluxes below the frond piles near the drainage ditches than from below the frond piles near the cover plants. Area-weighted upscaling gave plantation best estimates of Rtot, Rh, Ra of 0.158 ± 0.016, and 0.130 ± 0.036 and 0.029 ± 0.030 g CO2-C m−2 h−1, respectively. We conclude that spatial patterns impact root density, Ra and Rtot fluxes but not Rh fluxes.

ABSTRACTResilience has become increasingly popular in sustainability research and practice as a way to describe change. Within this discourse, the notion of resilience as the capacity of people, practices and processes, to persist, adapt or transform is particularly salient. The ability to bounce back from shock (persistence) or to take adaptive measures to cope with change are most commonly attributed to resilience, but at the same time, there is a strong push for a transformation agenda from various social and environmental movements. How capacities for resilience are enacted and performed through social practices remains relatively underexplored and there is potential for more dialogue and learning across disciplinary traditions. In this article, we outline the ‘Resilience Capacities Framework’ as a way to a) explicitly address questions of agency in how resilience capacities are enacted and b) account for the dynamic interactions between pathways of persistence, adaptation and transformation. Our starting point is to conceptualise future pathways as co-evolved, whereby social and ecological relationships are shaped through processes of selection, variation and retention, enacted in everyday practices. Drawing on theories of bricolage and structuration, we elaborate on the role of actors as bricoleurs, consciously and non-consciously shaping socio-ecological relationships and pathways of change. Informed by cases of rural change from mountain areas, we explore the extent to which an approach focusing on agency and bricolage can illuminate how the enactment of resilience capacities shapes intersecting pathways of change.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Background Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date. Aims To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. Method Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198. Results Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication). Conclusions The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Abstract Background Knowledge of pathogenic variants in cancer‐predisposing genes is important when making breast cancer treatment decisions, but genetic testing is not universal and criteria must be met to qualify for genetic testing. The objective of this study was to evaluate the pathogenic variant yield for nine cancer predisposition genes by testing criteria, singly and in combination. Methods Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four centers in Toronto, Canada. Participants completed a demographics and family history questionnaire and clinical characteristics were collected from medical charts. Genetic testing was done for BRCA1, BRCA2, PALB2, ATM, CHEK2, BRIP1, RAD51D, RECQL, and TP53. Pathogenic variant frequencies were calculated according to five criteria (age ≤ 50, triple‐negative breast cancer, family history, bilateral breast cancer, or Jewish ethnicity). Results Of the 1006 women studied, 100 women (9.9%) were found to have a pathogenic variant in one of the nine genes tested. The highest prevalence of pathogenic variants was found in women with triple‐negative breast cancer (23%). Of the 100 pathogenic variants detected, 78 were detected in women diagnosed at age 50 or less. A total of 96% of the mutations were identified with three criteria (age of diagnosis, family history, and triple‐negative status). Conclusions Genetic testing criteria for women with breast cancer should include women with triple‐negative breast cancer, regardless of age. All women aged 50 years or below at time of breast cancer diagnosis should be offered genetic testing.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.

This paper is concerned with how water prospectors, well diggers, and irrigation farmers come to know groundwater. Drawing on cases from Tanzania and Zimbabwe, the paper shows that much knowledge is derived from the close encounters with groundwater that occur through hard physical work, mediated by the use of lowcost tools and technologies. In this paper we show how this knowledge is embedded in everyday livelihoods, landscapes, and moral ecological rationalities. Through empirical material of such close encounters with groundwater, we make two interrelated points. Firstly, we draw attention to the importance of embodied forms of knowledge in shaping engagements with groundwater. Frequent close physical interactions with groundwater generate rich and intimate understandings of the changing quality and quantity of water flows. These understandings become primary ways in which people in communities know water, which is lively and sometimes invisible. Secondly, we argue that, though apparently mundane, reliant on low-cost technology, and highly localised, these encounters significantly shape broader socio-natural relationships in emerging groundwater economies. Amongst other examples, our data show groundwater prospectors monitoring the depth of borehole drilling in a shared aquifer in an attempt to ensure equitable access for different users. In concluding the paper, we reflect on the extent to which the knowledge and relationships formed through close physical encounters with groundwater have the potential to shape trajectories of groundwater management.

Abstract Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18–99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p

Obstructive sleep apnea (OSA), a common sleep disorder, poses significant challenges in perioperative management due to its complexity and multifactorial nature. With a global prevalence of approximately 22.6%, OSA often remains undiagnosed, and increases the risk of cardiac and respiratory postoperative complications. Preoperative screening has become essential in many institutions to identify patients at increased risk, and experts recommend proceeding with surgery in the absence of severe symptoms, albeit with heightened postoperative monitoring. Anesthetic and sedative agents exacerbate upper airway collapsibility and depress central respiratory activity, complicating intraoperative management, especially with neuromuscular blockade use. Additionally, OSA patients are particularly prone to opioid-induced respiratory depression, given their increased sensitivity to opioids and heightened pain perception. Thus, regional anesthesia and multimodal analgesia are strongly advocated to reduce perioperative complication risks. Postoperative care for OSA patients necessitates vigilant monitoring and tailored management strategies, such as supplemental oxygen and Positive Airway Pressure therapy, to minimize cardiorespiratory complications. Health care institutions are increasingly focusing on enhanced monitoring and resource allocation for patient safety. However, the rising prevalence of OSA, heterogeneity in disease severity, and lack of evidence for the efficacy of costly perioperative measures pose challenges. The development of effective screening and monitoring algorithms, alongside reliable risk predictors, is crucial for identifying OSA patients needing extended postoperative care. This review emphasizes a multidimensional approach in managing OSA patients throughout the perioperative period, aiming to optimize patient outcomes and minimize adverse outcomes.

Traumatic brain injury (TBI) is associated with an increased risk of developing Parkinson’s disease (PD), though the exact mechanisms remain unclear. TBI triggers acute neuroinflammation and catecholamine dysfunction post-injury, both implicated in PD pathophysiology. The long-term impact on these pathways following TBI, however, remains uncertain. In this study, male Sprague-Dawley rats underwent sham surgery or Marmarou’s impact acceleration model to induce varying TBI severities: single mild TBI (mTBI), repetitive mild TBI (rmTBI), or moderate–severe TBI (msTBI). At 12 months post-injury, astrocyte reactivity (GFAP) and microglial levels (IBA1) were assessed in the striatum (STR), substantia nigra (SN), and prefrontal cortex (PFC) using immunohistochemistry. Key enzymes and receptors involved in catecholaminergic transmission were measured via Western blot within the same regions. Minimal changes in these markers were observed, regardless of initial injury severity. Following mTBI, elevated protein levels of dopamine D1 receptors (DRD1) were noted in the PFC, while msTBI resulted in increased alpha-2A adrenoceptors (ADRA2A) in the STR and decreased dopamine beta-hydroxylase (DβH) in the SN. Neuroinflammatory changes were subtle, with a reduced number of GFAP+ cells in the SN following msTBI. However, considering the potential for neurodegenerative outcomes to manifest decades after injury, longer post-injury intervals may be necessary to observe PD-relevant alterations within these systems.

Abstract Mechanisms related to sub‐seabed fluid flow processes are complex and inadequately understood. Petrophysical properties, availability of gases, topography, stress directions, and various geological parameters determine the location and intensity of leakage which change over time. From tens of seafloor pockmarks mapped along Vestnesa Ridge on the west‐Svalbard margin, only six show persistent present‐day seepage activity in sonar data. To investigate the causes of such restricted gas seepage, we conducted a study of anisotropy within the conduit feeding one of these active pockmarks (i.e., Lunde Pockmark). Lunde is ∼400–500 m in diameter, and atop a ∼300–400 m wide seismic chimney structure. We study seismic anisotropy using converted S‐wave data from 22 ocean‐bottom seismometers (OBSs) located in and around the pockmark. We investigate differences in symmetry plane directions in anisotropic media using null energy symmetries in transverse components. Subsurface stress distribution affects fault/fracture orientations and seismic anisotropy, and we use S‐wave and high‐resolution 3D seismic data to infer stress regimes in and around the active seep site and study the effect of stresses on seepage. We observe the occurrence of changes in dominant fault/fracture and horizontal stress orientations in and around Lunde Pockmark and conclude minimum (NE‐SW) and maximum (SE‐NW) horizontal stress directions. Our analysis indicates a potential correlation between hydrofractures and horizontal stresses, with up to a ∼32% higher probability of alignment of hydrofractures and faults perpendicular to the inferred minimum horizontal stress direction beneath the Lunde Pockmark area.

Abstract Introduction Achieving sustained HIV viral suppression is a key strategy to optimize the health and wellbeing of those living with HIV. Sub‐optimal adherence to antiretroviral therapy (ART) in adolescents and young people living with HIV (AYPLHIV) in Southern Africa, due to a range of social and contextual factors, including poor mental health, has presented a substantial challenge to meeting targets aimed towards improving treatment outcomes and reducing transmission. With the increasing availability of viral load (VL) testing in Southern Africa, there is an opportunity to better understand the relationship between VL literacy, wellbeing and adherence among adolescents. Methods We conducted qualitative interviews with 45 AYPLHIV aged 10–24 years in three districts (urban, peri‐urban and rural) in Zimbabwe between March and August 2021. The sample was purposively selected to represent a range of experiences related to HIV status disclosure, gender, marital status and treatment experience. Separate workshops were conducted with 18 healthcare workers (HCWs) and 20 caregivers to better understand existing support mechanisms to AYPLHIV accessing ART. We used thematic analysis to examine adolescent VL literacy, treatment support networks, experiences of clinic interactions, VL testing procedures and barriers to adherence. Results VL literacy was consistently under‐developed among participants. Comprehension of phrases commonly heard during clinic visits, such as TND (target not detected) and “high” and “low” VL, were better understood by older participants. VL testing was predominantly understood as a clinical procedure that enables HCWs to monitor treatment adherence. Absent throughout the interviews were descriptions of how viral suppression improves health and quality of life, likely fosters wellbeing and enhances self‐esteem, enables participation in education and social activities, and eliminates the risk of onward transmission. Conclusions It is imperative that we reconsider how routine VL monitoring is communicated to and understood by AYPLHIV. Reframing ART, including VL test results, in terms of the psychosocial benefits that viral suppression can generate is likely to be crucial to motivating AYPLHIV to maintain optimal treatment engagement and develop self‐management approaches as they move into adulthood. Access to accurate information tailored to individual concerns and circumstances can support AYPLHIV to achieve wellbeing.

ObjectiveAlterations in regional neurometabolite levels as well as impaired neurodevelopmental outcomes have previously been observed in children who are HIV-exposed uninfected (CHEU). However, little is known about how neurometabolite profiles may relate to their developmental impairment. This study aimed to compare neurometabolite concentrations in school-aged CHEU and children who are HIV-unexposed (CHU) and to explore associations of neurometabolite profiles with functional neurodevelopment in the context of perinatal HIV exposure.MethodsWe used 3 T single voxel proton magnetic resonance spectroscopy (1H-MRS) to quantify absolute and relative neurometabolites in the parietal gray and parietal white matter in school-aged CHEU and aged- and community-matched CHU. Functional neurodevelopmental outcomes were assessed using the early learning outcome measure (ELOM) tool at 6 years of age.ResultsOur study included 152 school-aged children (50% males), 110 CHEU and 42 CHU, with an average age of 74 months at the neuroimaging visit. In an adjusted multiple linear regression analysis, significantly lower glutamate (Glu) concentrations were found in CHEU as compared to CHU in the parietal gray matter (absolute Glu, p = 0.046; Glu/total creatine (Cr+PCr) ratios, p = 0.035) and lower total choline to creatine ratios (GPC+PCh/Cr+PCr) in the parietal white matter (p = 0.039). Using factor analysis and adjusted logistic regression analysis, a parietal gray matter Glu and myo-inositol (Ins) dominated factor was associated with HIV exposure status in both unadjusted (OR 0.55, 95% CI 0.17–0.45, p = 0.013) and adjusted analyses (OR 0.59, 95% CI 0.35–0.94, p = 0.031). With Ins as one of the dominating metabolites, this neurometabolic factor was similar to that found at the age of two years. Furthermore, this factor was also found to be correlated with ELOM scores of gross motor development in CHEU (Pearson’s r = −0.48, p = 0.044). In addition, in CHEU, there was a significant association between Ins/Cr+PCr ratios in the parietal white matter and ELOM scores of fine motor coordination and visual motor integration in CHEU (Pearson’s r = 0.51, p = 0.032).ConclusionReduced Glu concentrations in the parietal gray matter may suggest regional alterations in excitatory glutamatergic transmission pathways in the context of perinatal HIV and/or antiretroviral therapy (ART) exposure, while reduced Cho ratios in the parietal white matter suggest regional myelin loss. Identified associations between neurometabolite profiles and gross and fine motor developmental outcomes in CHEU are suggestive of a neurometabolic mechanism that may underlie impaired motor neurodevelopmental outcomes observed in CHEU.

Abstract Background Chronic low back pain, a leading contributor to disease burden worldwide, is often caused by intervertebral disc (IVD) degeneration. Modic changes (MCs) are MRI signal intensity changes due to lesions in vertebral bone marrow adjacent to degenerated IVDs. Only a few studies described the histopathological changes associated with MC to date. MC type 1 is suggested to be associated with bone marrow infiltration of fibrovascular tissue, type 2 with fatty infiltration, and type 3 with bone sclerosis in humans. Methods This study investigated whether the dog can be a valuable animal model to research MCs, by examining the prevalence, imaging, and histological characteristics of lumbar MCs in dogs (340 dogs, 2496 spinal segments). Results Logistic regression analysis indicated that the presence of lumbosacral MCs was associated with age and disc herniation (annulus fibrosis protrusion and/or nucleus pulposus extrusion). According to MRI analysis, MCs were mostly detected at the lumbosacral junction in dogs. Most signal intensity changes represented MC type 3, while previous spinal surgery seemed to predispose for the development of MC type 1 and 2. Histological analysis (16 dogs, 39 spinal segments) indicated that IVDs with MCs showed more histopathological abnormalities in the endplate and vertebral bone marrow than IVDs without MCs. Mostly chondroid proliferation in the bone marrow was encountered, while the histologic anomalies described in humans associated with MCs, such as fibrovascular or fatty infiltration, were scarcely detected. Conclusions Dogs spontaneously develop MCs, but may exhibit other pathological processes or more chronic bone marrow pathologies than humans with MCs. Therefore, more research is needed to determine the translatability of the MCs encountered in dog low‐back‐pain patients.

Abstract Background Lineage‐tracing experiments have established that the central region of the mature intervertebral disc, the nucleus pulposus (NP), develops from the embryonic structure called “the notochord”. However, changes in the cells derived from the notochord which form the NP (i.e., notochordal cells [NCs]), in terms of their phenotype and functional identity from early developmental stages to skeletal maturation are less understood. These key issues require further investigation to better comprehend the role of NCs in homeostasis and degeneration as well as their potential for regeneration. Progress in utilizing NCs is currently hampered due to poor consistency and lack of consensus methodology for in vitro NC extraction, manipulation, and characterization. Methods Here, an international group has come together to provide key recommendations and methodologies for NC isolation within key species, numeration, in vitro manipulation and culture, and characterization. Results Recommeded protocols are provided for isolation and culture of NCs. Experimental testing provided recommended methodology for numeration of NCs. The issues of cryopreservation are demonstrated, and a pannel of immunohistochemical markers are provided to inform NC characterization. Conclusions Together we hope this article provides a road map for in vitro studies of NCs to support advances in research into NC physiology and their potential in regenerative therapies.