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Objective: Providing current, evidence-based information to cancer survivors is critical for informed decision making. People diagnosed with a rare cancer report higher unmet information needs compared to common cancer survivors. However, interventions providing informational support for rare cancers are limited. Therefore, the aims of this systematic review were to identify and synthesise interventions decreasing survivors' information needs and/or improving satisfaction with information, and to explore potential components to be included in an intervention for rare cancer survivors. Methods: Searches were conducted in PubMed, CINAHL, Embase, PsycINFO and the Cochrane Library. Studies reporting an intervention targeting information needs and/or patient satisfaction with information in survivors of any cancer type were included. Data were extracted, a quality assessment performed and findings were synthesised. Results: A total of 7012 studies were identified and 34 were included in the review. Five studies targeted patients with a rare cancer type; the remaining studies included common cancer survivors. Interventions varied in relation to the mode of information provision, timing of intervention delivery, and the intervention provider. The most promising interventions included face-to-face communication and written material and were delivered by a nurse. All rare cancer studies were designed around a web-based program, but none of them improved outcomes. Conclusions: Interventions targeting information needs and/or patient satisfaction with information in rare cancer survivors are lacking. Future studies should focus on this underserved group, and successful aspects of interventions for common cancer survivors should be considered for inclusion when designing an intervention for rare cancer survivors. [ABSTRACT FROM AUTHOR]

Purpose: There are several ways to include "disability" in research studies, which can be confusing or overwhelming for researchers, community members, and students. The aim of this paper is to share conceptualizations of disability and how to ask about "disability" in research studies. The paper provides a general introduction and brief analysis of the methodological approaches which can be used. Methods: We used reviews of the literature and extensive discussions to identify key articles, books, websites, and reports that provide guidance and examples of asking about disability in research. Results: Four primary approaches to asking study participants about disability were identified. For each of these, we provide background information, key points about the ways to use the approach including tools that have been developed, and example studies. A comparison table provides a high-level overview of similarities and differences in approaches. Other approaches and tools were also identified and are briefly described. Conclusion: Researchers involved in disability and rehabilitation research should be aware that there is not one best or singular way to ask about disability when conducting research. The approach or approaches chosen for a particular study need to match the purpose of the study. It is important that researchers take time to carefully consider their options and choose the best fit for their study. IMPLICATIONS FOR REHABILITATION: There are several different ways to ask about disability and functioning when conducting research that aims to include a disability component or focus. Researchers need to carefully select the best option(s) for their study. Whenever possible, researchers should use more than one approach and should allow for more than one type of disability or impairment to be selected. Researchers often require training to understand how to include disability in research. Allow adequate time and resources for training research team members so that the tools are implemented correctly. [ABSTRACT FROM AUTHOR]

This paper advances knowledge around the intersection of death, loss, and leisure travel. Our phenomenological study revealed the lived experiences of seven senior travelers who had traveled internationally following the death of a loved one(s). We employed the 'MeBox' method to help uncover new layers of meaning that are not always easy to put into words. The findings of our study provide new insights into notions of leisure by identifying overseas leisure travel within a liminal space in which feelings of loss and acceptance, and the creation of new perspectives, are experienced following the death of a loved one(s). Our findings challenge the destructive nature of human loss following death of a loved one(s). Instead, the experience of international travel appeared to influence the social, material, and existential life of senior travelers after the death of a loved one(s), transforming leisure into a personally meaningful experience for them. [ABSTRACT FROM AUTHOR]

This paper describes the use of mural-making as part of the knowledge mobilization activities of an international research partnership project. The mural depicts the technical and academic activities of people with disabilities in a university setting as meaningful action in inclusive research processes. The main objective of this 30-meter mural painting on a wall in the University of Bamenda was to demonstrate that inclusive research could encourage the inclusion and participation of people with disabilities in all areas of academic and professional activities of the university. A mural-making protocol was developed by the faculty and implemented by the team. It included the collection, analysis, and understanding of data on inclusion; design of drawings and the mural; wall preparation; plotting; and execution of the actual mural. The brightly colored mural now draws attention to inclusion, provides a vision of hopefulness, and complements the narrative character of inclusive education and research on campus. [ABSTRACT FROM AUTHOR]

Recognizing the inequities in developmental screening and services for children in immigrant families, a pediatric primary care clinic in partnership with a community-based early childhood program co-created a bicultural, bilingual early childhood developmental (ECD) family navigator program in Seattle, Washington. The primary aim of this study is to explore caregivers' perspectives about this program. Twenty-seven caregivers of young children participated in semi-structured interviews that were thematically analyzed. Three key themes were identified: 1) sharing language and culture, 2) facilitating accessibility, and 3) promoting development. Caregivers valued linguistic and cultural concordance between the navigator and the family, the navigator's approach to screening to improve accessibility and reduce barriers, and the focus on supporting early childhood development. Understanding caregivers' experience with the ECD family navigator development program and the aspects they value, informs clinic-based approaches to ensure families of diverse language and cultural backgrounds have accessible development screening and connection to services. [ABSTRACT FROM AUTHOR]

Purpose: To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery. Methods: This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling. Results: Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65–0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86–1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75–1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02–18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively. Conclusion: Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting. [ABSTRACT FROM AUTHOR]

Motivation: Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses. Implementation: We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later. General features: The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence. Availability: The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) with commissural alignment aims to limit the risk of coronary occlusion and maintain good coronary access. However, due to coronary origin eccentricity within the coronary cusp, coronary-commissural overlap (CCO) may still occur. TAVI using coronary alignment, rather than commissural alignment, may further improve coronary access. To compare rates of CCO after TAVI using commissural versus coronary alignment methodology. Cardiac CT scans from 102 patients with severe (tricuspid) aortic stenosis referred for TAVI were analysed. Native cusp asymmetry and coronary eccentricity were defined and used to simulate TAVI using commissural versus coronary alignment. Rates of optimal coronary alignment (< 10° from cusp centre) and severe misalignment (< 15° from coronary-commissural overlap) were compared. Additionally, the impact of valve misalignment during implantation was assessed. The native right coronary artery (RCA) origin was 15.8° (9.5 to 24°) closer to the right coronary cusp/non-coronary cusp (RCC-NCC) commissure than the centre of the right coronary cusp. The native left coronary artery (LCA) origin was 4.5° (0 to 11.5°) closer to the left coronary cusp/non-coronary cusp (LCC-NCC) commissure than the centre of the left coronary cusp (p < 0.01). Compared to commissural alignment, coronary alignment doubled the proportion of optimally-aligned RCAs (62/102 [60.8%] vs. 31/102 [30.4%]; p < 0.001), without a significant change in optimal LCA alignment (62/102 [60.8% vs. 74/102 [72.6%]; p = 0.07). There were no cases of severe misalignment with either strategy. Simulating 15° of valve misalignment resulted in severe RCA compromise risk in 7/102 (6.9%) of commissural alignment cases, compared to none using coronary alignment. Fluoroscopic projection was similar with both approaches. Coronary alignment resulted in a 2-fold increase of optimal TAVI positioning relative to the RCA ostium when compared to commissural alignment without impacting the LCA. Use of coronary alignment rather than commissural alignment may improve coronary access after TAVI and is less sensitive to valve rotational error, particularly for the right coronary artery. [ABSTRACT FROM AUTHOR]

Scholars have called for more critical considerations of social justice and tourism that align with the tenets, values, and practices for sustainability, transformation, and social change. The aim of this research was to map and critically assess the status of refugee-related research in tourism, particularly with regards to the extent to which it adopts, or extends, a social justice-oriented agenda. A systematic literature review of existing studies was conducted. Content analysis assessed three aspects of 37 studies, namely, (1) the topics covered, (2) the extent to which the research aligns with social justice research practices, and (3) the extent to which the research furthers the social justice agenda for transformation. The review revealed a body of work that does not demonstrate social justice research practices; mostly because the refugee-related research topics of focus do not exhibit a social justice-oriented agenda. Our review illustrated that existing tourism research tends to frame refugees negatively and as a threat to destinations, and neglect critical considerations of epistemologies, reflexivity, and research processes. We conclude by highlighting alternative approaches that could contribute to a social justice-oriented agenda, using tourism as a bridge for creating change within structures, discourses, and practices in refugee-related research. [ABSTRACT FROM AUTHOR]

Introduction Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. Methods SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. Results Participants were 81% Hispanic, with a mean (standard deviation [SD]) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p  = .015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two + smokers: 0.30 µg/m3 vs. One: 0.12 µg/m3 and Zero: 0.15 µg/m3; p  = .230). Conclusions Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. Implications This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure SHS exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects. [ABSTRACT FROM AUTHOR]

The focus of this project is to take advantage of the large NMR chemical shift anisotropy of 19F to determine the orientation of fluorine labeled biomolecules in situ in oriented biological systems such as muscle. The difficulty with a single fluorine atom is that the orientation determined from a chemical shift is not singlevalued in the case of a fully anisotropic chemical shift tensor. The utility of a labeling approach with two fluorine labels in a fixed molecular framework where one of the labels has an axially symmetric chemical shift anisotropy such as a CF3 group and the other has a fully asymmetric chemical shift anisotropy such as 5-fluorotryptophan is evaluated. The result is that the orientation of the label can be determined straightforwardly from a single one-dimensional 19F NMR spectrum. The potential applications are widespread and not limited to biological applications. [ABSTRACT FROM AUTHOR]

Background: Cancer patients have increased morbidity and mortality from COVID‐19, but may respond poorly to vaccination. The Evaluation of COVID‐19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS‐CoV‐2 community‐transmission setting, allows determination of vaccine response with minimal interference from infection. Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID‐19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre‐second vaccine dose and at 1, 3 (primary endpoint), and 6 months post‐second dose. SARS‐CoV‐2 anti‐spike‐RBD (S‐RBD) and anti‐nucleocapsid IgG antibodies were measured. Results: Ninety‐six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID‐19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p =.12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose. Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS‐CoV‐2 infection amplifies S‐RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID‐naïve population in studying vaccine immunogenicity. [ABSTRACT FROM AUTHOR]

Patients leave ED for a variety of reasons and at all stages of care. In Australian law, clinicians and health services owe a duty of care to people presenting to the ED for care, even if they have not yet entered a treatment space. There is also a positive duty to warn patients of material risks associated with their condition, proposed treatment(s), reasonable alternative treatment options and the likely effect of their healthcare decisions, including refusing treatment. This extends to a decision to leave the ED before care is completed. The form of that warning may vary based on what is known about the patient's condition and the associated risks at the time. Specific documentation of warnings given is essential. [ABSTRACT FROM AUTHOR]

We reviewed Australian mental health legislation to determine what obligations it places on psychiatrists to facilitate second opinions for compulsory patients who request them. Only four jurisdictions—Australian Capital Territory, Queensland, Victoria, and Western Australia—have legislated for 'patient-initiated' second opinions. Within these four regimes, there is variation in important aspects of the second opinion process, and there is a general absence of direction given to the second opinion providers. Based on research showing the variability of second opinion provision under New Zealand mental health legislation, we argue that this absence is likely to result in significant variation in the quality and depth of second opinions provided in Australia. We argue that New South Wales, the Northern Territory, South Australia, and Tasmania should consider formal provision for patient-initiated second opinions in their mental health legislation. We believe that such legislation ought to be aware of the barriers patients may face in accessing second opinions, and avoid exacerbating these barriers as Queensland's legislation appears to. Also, we argue that research on current practice in Australia should be conducted to better understand the effects of legislation on second opinions, and to help determine what amounts to best practice. [ABSTRACT FROM AUTHOR]

To navigate our complex social world, it is crucial to deploy multiple learning strategies, such as learning from directly experiencing action outcomes or from observing other people's behavior. Despite the prevalence of experiential and observational learning in humans and other social animals, it remains unclear how people favor one strategy over the other depending on the environment, and how individuals vary in their strategy use. Here, we describe an arbitration mechanism in which the prediction errors associated with each learning strategy influence their weight over behavior. We designed an online behavioral task to test our computational model, and found that while a substantial proportion of participants relied on the proposed arbitration mechanism, there was some meaningful heterogeneity in how people solved this task. Four other groups were identified: those who used a fixed mixture between the two strategies, those who relied on a single strategy and non-learners with irrelevant strategies. Furthermore, groups were found to differ on key behavioral signatures, and on transdiagnostic symptom dimensions, in particular autism traits and anxiety. Together, these results demonstrate how large heterogeneous datasets and computational methods can be leveraged to better characterize individual differences. People learn by observing others and from personal experience, but which strategy they favor varies. Here, the authors show that while some people dynamically arbitrate and switch to the strategy that is most reliable, others preferentially use one or a fixed mixture of strategies. [ABSTRACT FROM AUTHOR]

Background: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced. Methods: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables. Results: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0–3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures. Conclusions: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop ANcam, a novel method for identifying acanthosis nigricans (AN) using a smartphone camera and computer-aided color analysis for noninvasive screening of people with impaired glucose tolerance (IGT). Research Design and Methods: Adult and juvenile participants with or without diagnosed type 2 diabetes were recruited in Trinidad and Tobago. After obtaining informed consent, participants' history, demographics, anthropometrics, and A1C were collected and recorded. Three subject matter experts independently graded pictures of the posterior neck and upper back using the ANcam smartphone application and Burke methods. A correlation matrix investigated 25 color channels for association with hyperpigmentation, and the diagnostic thresholds were determined with a receiver operating characteristic curve analysis. Results: For the 227 participants with captured images and A1C values, the cyan/magenta/yellow/black (CMYK) model color channel CMYK_K was best correlated with IGT at an A1C cutoff of 5.7% (39 mmol/mol) (R = 0.45, P <0.001). With high predictive accuracy (area under the curve = 0.854), the cutoff of 7.67 CMYK_K units was chosen, with a sensitivity of 81.1% and a specificity of 70.3%. ANcam had low interrater variance (F = 1.99, P = 0.137) compared with Burke grading (F = 105.71, P <0.001). ANcam detected hyperpigmentation on the neck at double the self-reported frequency. Elevated BMI was 2.9 (95% CI 1.9–4.3) times more likely, elevated blood pressure was 1.7 (95% CI 1.2–2.4) times more likely, and greater waist-to-hip ratio was 2.3 (95% CI 1.4–3.6) times more likely with AN present. Conclusion: ANcam offers a sensitive, reproducible, and user-friendly IGT screening tool to any smartphone user that performs well with most skin tones and lighting conditions. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is frequently diagnosed among Canadian women. While targeted therapies are available for most BC patients; treatment resistance is common and novel therapeutic targets are of interest. Thyroid hormones (TH) bound to thyroid hormone receptors (THR) influence cell proliferation and differentiation; they are also involved in the growth and development of normal breast tissue. Evidence suggests that THRβ is a tumor suppressor in various solid tumors. Purpose: This narrative review discusses retrospective studies regarding the clinical relevance of THRβ as a potential prognostic biomarker and therapeutic target in BC. Methods: We consulted with an information specialist to develop a search strategy to find all literature related to THRα expression as a potential prognostic and therapeutic biomarker in breast cancer. The primary search was developed for Medline and translated to Embase. The searches were conducted on the Ovid platform on 18 August 2023. Results: Across seven retrospective studies identified, several have shown an association between higher THRβ1 expression with a lower risk of BC recurrence and with longer overall survival. Conclusions: Some evidence suggests that THRβ expression is associated with a lower risk of BC recurrence and death. Validation of THRβ as an independent prognostic biomarker and possible predictive biomarker of response to endocrine therapy and/or chemotherapy is of interest. Given that THRβ is upstream of the AKT/PI3K pathway, its potential as a predictive biomarker of response to AKT inhibitors and/or PI3K inhibitors may also be of value. Finally, the potential re-purposing of THRβ agonists as anti-cancer agents warrants investigation. [ABSTRACT FROM AUTHOR]

by Siu Loon Hoe. CRC Press is an imprint of Taylor & Francis Group, LLC. 2023 141 p. ISBN: 9781032112534By Tom CockburnReported by Author [Extracted from the article]

Objectives: To investigate the effect of the COVID‐19 pandemic on prostate cancer incidence, prevalence, and mortality in England. Patients and Methods: With the approval of NHS England and using the OpenSAFELY‐TPP dataset of 24 million patients, we undertook a cohort study of men diagnosed with prostate cancer. We visualised monthly rates in prostate cancer incidence, prevalence, and mortality per 100 000 adult men from January 2015 to July 2023. To assess the effect of the pandemic, we used generalised linear models and the pre‐pandemic data to predict the expected rates from March 2020 as if the pandemic had not occurred. The 95% confidence intervals (CIs) of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results: In 2020, there was a drop in recorded incidence by 4772 (31%) cases (15 550 vs 20 322; 95% CI 19 241–21 403). In 2021, the incidence started to recover, and the drop was 3148 cases (18%, 17 950 vs 21 098; 95% CI 19 740–22 456). By 2022, the incidence returned to the levels that would be expected. During the pandemic, the age at diagnosis shifted towards older men. In 2020, the average age was 71.6 (95% CI 71.5–71.8) years, in 2021 it was 71.8 (95% CI 71.7–72.0) years as compared to 71.3 (95% CI 71.1–71.4) years in 2019. Conclusions: Given that our dataset represents 40% of the population, we estimate that proportionally the pandemic led to 20 000 missed prostate cancer diagnoses in England alone. The increase in incidence recorded in 2023 was not enough to account for the missed cases. The prevalence of prostate cancer remained lower throughout the pandemic than expected. As the recovery efforts continue, healthcare should focus on finding the men who were affected. The research should focus on investigating the potential harms to men diagnosed at older age. [ABSTRACT FROM AUTHOR]

Background: Organophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans. Methods: We recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray–Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders. Results: OP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6. Conclusion: In support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans. [ABSTRACT FROM AUTHOR]

This article outlines a novel approach for career readiness which embeds a global engagement trip within a social entrepreneurship course. Utilizing an empathy driven approach, the instructional innovation exposes students to social impact and innovation in an entrepreneurial setting, provides an opportunity for rich engagements with social and micro-entrepreneurs, and facilitates connection with self and others. Reflexive assignments and dialogues are integrated throughout the instructional innovation allowing students to identify and reflect on their aspirations and intentions for creating societal impact in their career journeys. Participation in this experience has resulted in outcomes related to career goals, including new plans for building social impact into work and renewed social entrepreneurial intentions. Instructions, exercises, and evidence of their effectiveness are provided. [ABSTRACT FROM AUTHOR]

Background and Aims: To determine the level of diagnostic agreement between remote and face‐to‐face consultation in assessing shoulder complaints. Methods: A retrospective service evaluation with three groups of patient data; those assessed only face‐to‐face (group 1), remotely then face‐to‐face (group 2), remotely only (group 3). Patient data were extracted from 6 secondary care shoulder Advanced Physiotherapy Practitioner's (APPs) records, covering six sites. Three‐hundred‐and‐fifty‐nine sets of patient data were included in the final evaluation. The main outcome measure was the percentage of agreement between diagnosis at initial and follow‐up consultation, when assessed by APPs across the three groups. A Pearson χ2 test was used to assess the relationship between the method of consultation and the level of diagnostic agreement. Diagnoses were categorized as either the same, similar, or different by an independent APP. Secondary outcome measures investigated whether age or the length of time between appointments had any effect in determining the level of diagnostic concordance. Results: There was exact agreement of 77.05% and 85.52% for groups 1 and 3, respectively, compared with 34.93% for patient data in group 2. Similar clinical impressions across both initial and follow‐up were seen 16.39% of the time in group 1, 7.24% of the time in group 3, and 36.99% in group 2. Lastly, the percentage of times a diagnosis was changed between initial and review appointments occurred in only 6.56% of group 1 contacts, 7.24% of group 3 contacts, but 28.08% of the time in group 2. Conclusion: There was a large mismatch in the diagnosis of musculoskeletal shoulder complaints, when patients are initially assessed remotely and then followed‐up in‐person. This has implications for the future provision of shoulder assessment in physiotherapy. [ABSTRACT FROM AUTHOR]

The value and uncertainty associated with choice alternatives constitute critical features relevant for decisions. However, the manner in which reward and risk representations are temporally organized in the brain remains elusive. Here we leverage the spatiotemporal precision of intracranial electroencephalography, along with a simple card game designed to elicit the unfolding computation of a set of reward and risk variables, to uncover this temporal organization. Reward outcome representations across wide-spread regions follow a sequential order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We further highlight the role of the anterior insula in generalizing between reward prediction error and risk prediction error codes. Together our results emphasize the importance of neural dynamics for understanding value-based decisions under uncertainty. It is unclear how reward and risk are temporally organized in the human brain. Here, the authors demonstrate both sequential and parallel encoding of decision variables, and the role of anterior insula in reward- and risk-prediction error. [ABSTRACT FROM AUTHOR]

CD11c+ atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here, we identified candidate transcription factors associated with the ABC population based on a human tonsillar B cell single-cell dataset. We identified CD11c+ B cells in mice with a similar transcriptomic signature to human ABCs, and using an optimized CRISPR-Cas9 knockdown screen, we observed that loss of zinc finger E-box binding homeobox 2 (Zeb2) impaired ABC formation. Furthermore, ZEB2 haplo-insufficient Mowat-Wilson syndrome (MWS) patients have decreased circulating ABCs in the blood. In Cd23Cre/+Zeb2fl/fl mice with impaired ABC formation, ABCs were dispensable for efficient humoral responses after Plasmodium sporozoite immunization but were required to control recrudescent blood-stage malaria. Immune phenotyping revealed that ABCs drive optimal T follicular helper (TFH) cell formation and germinal center (GC) responses and they reside at the red/white pulp border, likely permitting better access to pathogen antigens for presentation. Collectively, our study shows that ABC formation is dependent on Zeb2, and these cells can limit recrudescent infection by sustaining GC reactions. Editor's summary: CD11c+ atypical B cells (ABCs) have been linked to chronic infections, like malaria and HIV, and autoimmune disorders, but little is known about their development. Gao et al. identified zinc finger E-box binding homeobox 2 (Zeb2) as a key transcription factor for ABC formation through analysis of human tonsillar B cells and ZEB2 haplo-insufficient individuals with Mowat-Wilson syndrome, with validation in mouse models of Plasmodium vaccination or infection. ABCs could facilitate the presentation of parasite antigens, which likely aids T follicular helper cell activation and the maintenance of germinal center (GC) reactions. These findings highlight the role of Zeb2 in ABC development and their contribution to GC responses. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Background: Examining lung cancer (LC) cases in Virginia (VA) is essential due to its significant public health implications. By studying demographic, environmental, and socioeconomic variables, this paper aims to provide insights into the underlying drivers of LC prevalence in the state adjusted for spatial associations at the zipcode level. Methods: We model the available VA zipcode-level LC counts via (spatial) Poisson and negative binomial regression models, taking into account missing covariate data, zipcode-level spatial association and allow for overdispersion. Under latent Gaussian Markov Random Field (GMRF) assumptions, our Bayesian hierarchical model powered by Integrated Nested Laplace Approximation (INLA) considers simultaneous (spatial) imputation of all missing covariates through elegant prediction. The spatial random effect across zip codes follows a Conditional Autoregressive (CAR) prior. Results: Zip codes with elevated smoking indices demonstrated a corresponding increase in LC counts, underscoring the well-established connection between smoking and LC. Additionally, we observed a notable correlation between higher Social Deprivation Index (SDI) scores and increased LC counts, aligning with the prevalent pattern of heightened LC prevalence in regions characterized by lower income and education levels. On the demographic level, our findings indicated higher LC counts in zip codes with larger White and Black populations (with Whites having higher prevalence than Blacks), lower counts in zip codes with higher Hispanic populations (compared to non-Hispanics), and higher prevalence among women compared to men. Furthermore, zip codes with a larger population of elderly people (age ≥ 65 years) exhibited higher LC prevalence, consistent with established national patterns. Conclusions: This comprehensive analysis contributes to our understanding of the complex interplay of demographic and socioeconomic factors influencing LC disparities in VA at the zip code level, providing valuable information for targeted public health interventions and resource allocation. Implementation code is available at GitHub. [ABSTRACT FROM AUTHOR]

We show how to reduce the computational time of the practical implementation of the Raviart-Thomas mixed method for second-order elliptic problems. The implementation takes advantage of a recent result which states that certain local subspaces of the vector unknown can be eliminated from the equations by transforming them into stabilization functions; see the paper published online in JJIAM on August 10, 2023. We describe in detail the new implementation (in MATLAB and a laptop with Intel(R) Core (TM) i7-8700 processor which has six cores and hyperthreading) and present numerical results showing 10 to 20% reduction in the computational time for the Raviart-Thomas method of index k , with k ranging from 1 to 20, applied to a model problem. We show how to reduce the computational time of the practical implementation of the Raviart-Thomas mixed method for second-order elliptic problems. The implementation takes advantage of a recent result which states that certain local subspaces of the vector unknown can be eliminated from the equations by transforming them into stabilization functions; see the paper published online in JJIAM on August 10, 2023. We describe in detail the new implementation (in MATLAB and a laptop with Intel(R) Core (TM) i7-8700 processor which has six cores and hyperthreading) and present numerical results showing 10 to 20% reduction in the computational time for the Raviart-Thomas method of index , with ranging from 1 to 20, applied to a model problem. [ABSTRACT FROM AUTHOR]

Background Paraquat dichloride is currently among the most widely used commercial herbicides in the USA. In the present study, we provide epidemiological assessment of ambient paraquat exposure and Parkinson's disease (PD) risk in a population-based study of PD in agricultural regions of Central California. Methods Based on 829 PD patients and 824 community controls, we assessed associations between ambient paraquat dichloride exposure and PD. We estimated residential and workplace proximity to commercial agricultural applications in three California counties since 1974 using the CA pesticide use reporting (PUR) data and land use maps. We evaluated any, duration and average intensity [pounds (0.45 kilograms) per acre per year] of exposure for paraquat in four time windows. Results Ambient paraquat exposure assessed at both residence and workplace was associated with PD, based on several different exposure measures. The PD patients both lived and worked near agricultural facilities applying greater amounts of the herbicide than community controls. For workplace proximity to commercial applications since 1974, working near paraquat applications every year in the window [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.46, 3.19] and a higher average intensity of exposure [per 10 pounds (4.54 kilograms), OR = 2.08, 95% CI = 1.31, 3.38] were both associated with an increased odds of PD. Similar associations were observed for residential proximity (duration: OR = 1.91, 95% CI = 1.30, 2.83; average intensity: OR = 1.72, 95% CI = 0.99, 3.04). Risk estimates were comparable for men and women, and the strongest odds were observed for those diagnosed at ≤60 years of age. Conclusion This study provides further indication that paraquat dichloride exposure increases the risk of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Autosomal recessive polycystic kidney disease is an early onset inherited hepatorenal disorder affecting around 1 in 20,000 births with no approved specific therapies. The disease is almost always caused by variations in the polycystic kidney and hepatic disease 1 gene, which encodes fibrocystin (FC), a very large, single‐pass transmembrane glycoprotein found in primary cilia, urine and urinary exosomes. By comparison to proteins involved in autosomal dominant PKD, our structural and molecular understanding of FC has lagged far behind such that there are no published experimentally determined structures of any part of the protein. Bioinformatics analyses predict that the ectodomain contains a long chain of immunoglobulin‐like plexin‐transcription factor domains, a protective antigen 14 domain, a tandem G8‐TMEM2 homology region and a sperm protein, enterokinase and agrin domain. Here we review current knowledge on the molecular function of the protein from a structural perspective. [ABSTRACT FROM AUTHOR]

Disability is very common and yet not well understood within sub-Saharan African countries. There has been growing attention to the use of research evidence to improve social inclusion of persons living with disabilities. This article reports on a process that can be used to monitor and evaluate evidence databases to encourage improvements in website and content accessibility for people with disabilities. We examined five evidence communities' online databases by: (1) assessing the accessibility of these website databases; and (2) assessing the resources within these websites. Finally, we aimed to provide feedback from the evaluation to these evidence databases. We carried out a cross-sectional study of the online evidence databases using the Web Content Accessibility Guidelines - a universal standard for web content accessibility assessment. We assessed access to the databases using a purposive sample of 25 resources within them. Resources are meant to improve practice, policy and decision making for all, including people with disabilities. They include systematic reviews, reports and articles. Accessibility is being able to obtain, understand and use resources; addressing barriers that could hinder this is important. Even though these evidence databases are considered as enabling inclusion and diversity within the evidence ecosystem, their contents are not fully accessible to people with disabilities, and they only partially met the recommendations of the Web Content Accessibility Guidelines. [ABSTRACT FROM AUTHOR]

The Tsitsa River catchment is a complex social-ecological system (cSES) in a rural area of the Eastern Cape Province of South Africa and the site of the Tsitsa Project (TP); a multi-stakeholder, transdisciplinary landscape restoration project aiming to improve sustainable livelihoods and ecological infrastructure. We investigated transformation mechanisms in a framing of multidimensional linkages, including the recognition of differentiated scales and levels. Linkages were analysed through the development of two vignettes: 1) a citizen technician employed to monitor sediment loads in rivers to inform landscape restoration activities (local scale); and 2) a senior government official responsible for (regional scale) operational and on-the-ground restoration initiatives. Vignette data were generated during a workshop, from TP researcher reflexivity, and interviews with the TP Catchment Coordinator and vignette subjects. Data were analysed and presented: i) as a heuristic diagram, ii) through a narrative, and iii) as a matrix table. Each analysis incorporated a different conceptualisation of scale in relation to four social processes related to transformative change: learning, agency, power and structure. Transformation is demonstrated and leverage points and areas of intractability for promoting and constraining future transformation towards social-ecological sustainability, were identified respectively. Further, we suggest that an understanding of transformative processes was enriched and nuanced by combining a triad of complementary analytical exercises. These allowed a focus on unique stories and contexts, but also the identification of generalisable patterns and mechanisms. [ABSTRACT FROM AUTHOR]

The importance of collaborative approaches to governing social-ecological systems (SES) towards more transformative outcomes is now widely acknowledged. Theoretical and meth- odological frameworks to enable such collaborations are being developed across a range of disciplines. Transdisciplinary approaches are emerging as a key enabler of potentially trans- formative collaborations in SES, particularly where these are characterized by 'multiple multi- ples' (e.g. multiple scales, knowledge systems, etc.). A typical approach to studying complex collaborative initiatives across a range of contexts is comparative case study research, often relying on researchers embedded in cases. In this approach, qualitative case studies are coded using predetermined variables (based on ecological, social, and social-ecological features of cases) to enable comparison and cross-case analysis. In our experience, the process of coding qualitative cases into a quantitative analysis framework can be hampered by what we term 'sticky variables', i.e. variables which are difficult to code for reasons related to aspects of the intrinsic complexity of social-ecological systems. Based on cases from a range of geographic locations across the Global North and South, we identify sticky variables, and elucidate the reasons for their 'stickiness'. We propose several ways of working with and learning from sticky variables, and we reflect on theoretical, methodological and reflexive aspects of transdisciplinary research on collaborations. Moreover, we suggest that sticky variables might be 'flags' for interesting underlying factors that influence collaboration. We conclude by drawing out recommendations for researchers and practitioners confronted with the complexities and nuances of collaborations in social-ecological systems around the world. [ABSTRACT FROM AUTHOR]

Sustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable, just and equitable futures. This paper synthesises insights from the development of a community of practice on social-ecological systems (SES) research in southern Africa over the past decade, linked to the international Programme on Ecosystem Change and Society (PECS). This community consists of a network of researchers who carry out place-based SES research in the southern African region. They interact through various cross-cutting working groups and also host a variety of public colloquia and student and practitioner training events. Known as the Southern African Program on Ecosystem Change and Society (SAPECS), its core objectives are to: (1) derive new approaches and empirical insights on SES dynamics in the southern African context; (2) have a tangible impact by mainstreaming knowledge into policy and practice; and (3) grow the community of practice engaged in SES research and governance, including researchers, students and practitioners. This paper reflects on experiences in building the SAPECS community, with the aim of supporting the development of similar networks elsewhere in the world, particularly in the Global South. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy is often described as a pivotal life stage for women, where regular contact with health professionals may play an important role in lifestyle awareness. This study explored the knowledge, practices, and beliefs of health professionals and pregnant women regarding physical activity and weight management during the antenatal period. Methods: A qualitative study was undertaken in southeastern Australia using individual interviews. Recruitment sought women of gestation >12 weeks, experiencing an uncomplicated pregnancy (n = 6), and antenatal health professionals including midwives (n = 4) and an obstetrician (n = 1). Data were analysed using Interpretive Phenomenological Analysis. Results: Three major themes emerged: (1) women rely on multiple sources of pregnancy-related healthy lifestyle information; (2) discussions around healthy lifestyle behaviours are low priority and often inconsistent; and (3) lifestyle-related topics perceived as sensitive make some conversations and actions difficult. Conclusions: Pregnant women expressed gaps in lifestyle-related knowledge and education being provided by health professionals. In turn, health professionals expressed difficulty discussing sensitive topics such as weight with pregnant women and had limited knowledge of pregnancy-specific physical activity guidelines. The themes generated by this study may form the foundation for further research to inform clinical policy and practice regarding advice in antenatal care. [ABSTRACT FROM AUTHOR]

This paper identifies a new discourse about tourism, that of final wish making. The website communications of charitable foundations whose dedicated purpose is to grant final wishes for adults with a terminal illness and their families were examined using critical discourse analysis. Specifically, the aim of this study was to understand how these charitable organisations construct, communicate and mediate meanings around terminal illness and travel for these individuals. Our study found that, promoted as a final wish in one's life, tourism is framed as a transformational concept that is beneficial in the imminent time before death, as a legacy for life, and after death. Our analysis indicated implications around the memory-making potential of tourism and the differential power relations between final wish organisers and vulnerable individuals with a terminal illness. The paper calls for further research exploring the marginalisation of the terminally ill through tourism, but equally the potential of tourism to include the most vulnerable tourists in their final days. [ABSTRACT FROM AUTHOR]

Every day in EDs, clinicians are faced with situations where they need to decide whether to detain a patient for assessment and treatment. For patients who meet the relevant criteria, provisions of mental health legislation can be used. For other patients, clinicians often rely on so‐called 'duty of care'. This article briefly explores this complex area of law, including the relevant legislation, common law principles and grey areas. It also proposes an approach to decision‐making in this area. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate‐specific membrane antigen (PSMA)‐based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. Materials and Methods: This was a cross‐sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18F‐DCFPyL‐PSMA‐PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. Results: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy‐eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44–14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. Conclusions: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18F‐DCFPyL‐PET/CT. pT3b disease was associated with 4.31‐fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles. [ABSTRACT FROM AUTHOR]

Vaccination strategies in mice inducing high numbers of memory CD8+ T cells specific to a single epitope are able to provide sterilizing protection against infection with Plasmodium sporozoites. We have recently found that Plasmodium-specific CD8+ T cells cluster around sporozoite-infected hepatocytes but whether such clusters are important in elimination of the parasite remains incompletely understood. Here, we used our previously generated data in which we employed intravital microscopy to longitudinally image 32 green fluorescent protein (GFP)-expressing Plasmodium yoelii parasites in livers of mice that had received activated Plasmodium-specific CD8+ T cells after sporozoite infection. We found significant heterogeneity in the dynamics of the normalized GFP signal from the parasites (termed 'vitality index' or VI) that was weakly correlated with the number of T cells near the parasite. We also found that a simple model assuming mass-action, additive killing by T cells well describes the VI dynamics for most parasites and predicts a highly variable killing efficacy by individual T cells. Given our estimated median per capita kill rate of k = 0.031/h we predict that a single T cell is typically incapable of killing a parasite within the 48 h lifespan of the liver stage in mice. Stochastic simulations of T cell clustering and killing of the liver stage also suggested that: (i) three or more T cells per infected hepatocyte are required to ensure sterilizing protection; (ii) both variability in killing efficacy of individual T cells and resistance to killing by individual parasites may contribute to the observed variability in VI decline, and (iii) the stable VI of some clustered parasites cannot be explained by measurement noise. Taken together, our analysis for the first time provides estimates of efficiency at which individual CD8+ T cells eliminate intracellular parasitic infection in vivo. [ABSTRACT FROM AUTHOR]