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Vocal communication depends on distinguishing self-generated vocalizations from other sounds. Vocal motor corollary discharge (CD) signals are thought to support this ability by adaptively suppressing auditory cortical responses to auditory feedback. One challenge is that vocalizations, especially those produced during courtship and other social interactions, are accompanied by other movements and are emitted during a state of heightened arousal, factors that could potentially modulate auditory cortical activity. Here, we monitor auditory cortical activity, ultrasonic vocalizations (USVs), and other non-vocal courtship behaviors in a head-fixed male mouse while he interacts with a female mouse. This approach reveals a vocalization-specific signature in the auditory cortex that suppresses the activity of USV playback-excited neurons, emerges before vocal onset, and scales with USV band power. Notably, this vocal modulatory signature is also present in the auditory cortex of congenitally deaf mice, revealing an adaptive vocal CD signal that manifests independently of auditory feedback or auditory experience., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Women sex workers face substantial health inequities due to structural barriers including criminalisation and stigma. Stigma has been associated with HIV-related inequities among marginalised populations, however, we know less about the impacts of sex work-specific occupational stigma on HIV/sexually transmitted infection (STI) risk among women sex workers. Given these research gaps and the disproportionate burden of stigma faced by sex workers, we evaluated the association between sex work occupational stigma and recent inconsistent condom use with clients, over an 8-year period (2014-2022)., Methods: Baseline and semiannual questionnaire data from a prospective, community-based cohort of sex workers in Vancouver, Canada from September 2014 to February 2022 were used. We employed complete-case bivariate and multivariate logistic regression analysis using generalised estimating equations to analyse the relationship between sex work occupational stigma and inconsistent condom use for vaginal/anal sex with clients in the past 6 months., Results: Among 574 participants, the cumulative prevalence of inconsistent condom use by clients and sex work occupational stigma in the last 6 months was 32.1% (n=184) and 59.9% (n=344), respectively, over the 8-year period. In adjusted multivariable analysis, exposure to sex work occupational stigma was associated with almost twofold increased odds of recent inconsistent condom use with clients (adjusted OR 1.93, 95% CI 1.23 to 3.03) over the 8-year period., Conclusion: Multilevel interventions addressing the role of occupational stigma are needed for HIV and STI prevention efforts, including scale-up of sex worker-led/delivered sexual health services and structural changes to decriminalise and destigmatise sex work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Since the beginning of the COVID-19 pandemic, COVID-19 risk mitigation measures have expanded to include increased rules and surveillance in supportive housing. Yet, in the context of the dual public health emergencies of COVID-19 and the unregulated drug toxicity crisis, we have not evaluated the unintended health and social consequences of such measures, especially on criminalized women. In order to address this dearth of evidence, our aim was to assess the association between increased housing rules and surveillance during COVID-19 and (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal among women sex workers who use drugs in Vancouver, BC., Methods: This study is nested within An Evaluation of Sex Workers Health Access (AESHA), a community-based prospective cohort of women sex workers in Metro Vancouver (2010-present). Using cross-sectional data collected during the first year of COVID-19 (April 2020-2021), we developed separate multivariable logistic regression confounder models to examine the independent associations between experiencing increased housing rules and surveillance during COVID-19 on (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal in the last 6 months., Results: Amongst 166 participants, 10.8% reported experiencing a recent non-fatal overdose and 31.3% recently administered naloxone for overdose reversal. 56.6% reported experiencing increased rules and surveillance within their housing during COVID-19. The prevalence of non-fatal overdose and administering naloxone was significantly elevated among those exposed to increased housing rules and surveillance during COVID-19 versus those who were unexposed (83.3% vs. 52.1%; 75.0% vs. 48.2%, respectively). In separate multivariate confounder models, exposure to increased housing rules and surveillance during COVID-19 was independently associated with increased odds of administering naloxone [AOR: 3.66, CI: 1.63-8.21], and marginally associated with non-fatal overdose [AOR: 3.49, CI: 0.92-13.27]., Conclusion: Efforts to prioritize the right to safe, adequate and affordable housing must avoid reinforcing an overly coercive reliance on surveillance measures which, while often well-intended, can negatively shape residents' well-being. Furthermore, public health responses to pandemics must include criminalized populations so that measures do not exacerbate overdose risk. Implementation of a regulated drug supply is recommended, alongside housing policies that promote residents' rights, safety, and health., (© 2024. The Author(s).)

Introduction: The tobacco industry has a long history of circumventing regulations to present their products, inaccurately, as less harmful. Greenwashing (portraying a product as natural/eco-friendly) is increasingly used by tobacco companies and may mislead consumers to believe that certain cigarettes are less harmful than others. This study assesses the effect of some common greenwashing tactics on consumer product perceptions., Methods: We conducted an online experiment with 1,504 participants ages 18-29, randomized to view a cigarette ad manipulated for presence/absence of a combination of 4 different greenwashing techniques: greenwashed ad text, greenwashed ad imagery, recycled paper ad background, and image of greenwashed cigarette pack. Participants rated perceived absolute harm, relative harm to other cigarettes, absolute addictiveness, relative addictiveness, and relative nicotine content., Results: Participants who viewed ads containing greenwashed text were more likely to have inaccurate perceptions about absolute harm (AOR=1.72), relative harm (AOR=3.92), relative addictiveness (AOR=2.93) and nicotine content (AOR=2.08). Participants who viewed ads containing greenwashed imagery were more likely to have inaccurate perceptions of relative harm (AOR=1.55), absolute addictiveness (AOR=1.72), relative addictiveness (AOR=1.60) and nicotine content (AOR=1.48). Forty-two percent of those who saw an ad with all greenwashed features believed the product was less harmful than other cigarettes vs. 2% of those who saw an ad without greenwashed features., Conclusions: We found greenwashed text and imagery produced inaccurate risk perceptions. More active U.S. Food & Drug Administration (FDA) enforcement against such greenwashing and new FDA rulemaking to prohibit unnecessary imagery in tobacco advertising and establish plain packaging requirements would help protect consumers and public health., Implications: These findings provide evidence that greenwashing tactics used by the tobacco industry increase inaccurate product risk perceptions. These tactics could be a way for the industry to make implicit modified risk claims, despite applicable U.S. Family Smoking Prevention and Tobacco Control Act prohibitions. Findings from this study support the need for prohibitions on these tactics, and the potential for such prohibitions to help protect public health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction and Hypothesis: Many patients develop bladder symptoms after radical hysterectomy. This study compared urinary outcomes following radical hysterectomy based on trial of void (TOV) timing (pre-discharge TOV versus post-discharge TOV)., Methods: A retrospective non-inferiority study of patients at two academic tertiary referral centers who underwent radical hysterectomy between January 2010 and January 2020 was carried out. Patients were stratified according to timing of postoperative TOV: either pre-discharge or post-discharge from the hospital. Short-term urinary outcomes (including passing TOV, representation with retention) and long-term de novo urinary dysfunction (defined as irritative voiding symptoms, urgency, frequency, nocturia, stress or urgency incontinence, neurogenic bladder, and/or urinary retention) were extracted from the medical record. We hypothesized that the proportion of patients who failed pre-discharge TOV would be within a 15% non-inferiority margin of post-discharge TOV., Results: A total of 198 patients underwent radical hysterectomy for cervical (118 out of 198; 59.6%), uterine (36 out of 198; 18.2%), and ovarian (29 out of 198; 14.6%) cancer. One hundred and nineteen patients (119 out of 198, 60.1%) underwent pre-discharge TOV, of whom 14 out of 119 (11.8%) failed. Of the post-discharge TOV patients (79 out of 198, 39.9%), 5 out of 79 (6.3%) failed. The proportion of patients who failed a pre-discharge TOV was within the non-inferiority margin (5.4% difference, p = 0.23). A greater proportion of patients in the post-discharge TOV group developed long-term de novo urinary dysfunction (27.2% difference, p = 0.005). Median time to diagnosis of de novo urinary dysfunction was 0.5 years (range 0-9) in the pre-discharge TOV group versus 1.0 year (range 0-6) in the post-discharge TOV group (p > 0.05)., Conclusions: In this study, pre-discharge TOV had non-inferior short-term outcomes and improved long-term outcomes., (© 2024. The International Urogynecological Association.)

Counterfactual theories propose that people's capacity for causal judgment depends on their ability to consider alternative possibilities: The lightning strike caused the forest fire because had it not struck, the forest fire would not have ensued. To accommodate a variety of psychological effects on causal judgment, a range of recent accounts have proposed that people probabilistically sample counterfactual alternatives from which they compute a graded measure of causal strength. While such models successfully describe the influence of the statistical normality (i.e., the base rate) of the candidate and alternate causes on causal judgments, we show that they make further untested predictions about how normality influences people's confidence in their causal judgments. In a large (N = 3,020) sample of participants in a causal judgment task, we found that normality indeed influences people's confidence in their causal judgments and that these influences were predicted by a counterfactual sampling model in which people are more confident in a causal relationship when the effect of the cause is less variable among imagined counterfactual possibilities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: The coronavirus (COVID-19) pandemic resulted in the rapid implementation of remote consultations to maintain musculoskeletal physiotherapy services. However, little is known about UK musculoskeletal physiotherapists' experiences of providing services during the COVID-19 pandemic., Objectives: To explore musculoskeletal physiotherapists' experiences of using remote consultations in one area of England during the COVID-19 pandemic., Design: Qualitative study using hermeneutic phenomenology based on the approach of Gadamer., Methods: Semi-structured interviews with twelve musculoskeletal physiotherapists were conducted online using Microsoft Teams. Data were analysed using frameworks based on the philosophical concepts of Gadamer's hermeneutics., Findings: Musculoskeletal physiotherapists' experience of using remote consultations during the COVID-19 pandemic was framed by three concepts: therapeutic relationship, transformational change, and uncertainty. These concepts are underpinned by four main themes capturing their experiences: (1) Disconnection: Difficulties building a rapport and reduced non-verbal communication affected building an effective therapeutic relationship, (2) Necessity: Transformation of services to remote consultations was positive, although technology and connectivity issues had a negative impact, (3) Loss of control: Diagnostic uncertainty, being unprepared, and experience affected physiotherapists' clinical practice, (4) Protection: Peer support and the use of technology facilitated a feeling of protection for physiotherapists., Conclusion: The findings of this study contribute to a better understanding of musculoskeletal physiotherapists' experience of using remote consultations during the COVID-19 pandemic. Implications for practice include the need to provide training for all musculoskeletal physiotherapists and undergraduates to enable the effective delivery of remote physiotherapy. Furthermore, digital infrastructure should be optimised to support future delivery of remote musculoskeletal physiotherapy services., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets., Competing Interests: Conflict of interest: M.D.J. Neilly reports lecture honoraria from Bristol-Myers Squibb, outside the submitted work. J. Pearson reports lecture honoraria from Bristol-Myers Squibb, outside the submitted work. A.W. Thu reports lecture honoraria from Bristol-Myers Squibb, outside the submitted work. C. MacRae reports lecture honoraria from Bristol-Myers Squibb, outside the submitted work. K.G. Blyth reports grants or contracts from Rocket Medical, and RS Oncology, outside the submitted work; Lecture honoraria from Bristol-Myers Squibb, outside the submitted work., (Copyright ©ERS 2024.)

Introduction: Varenicline helps people who smoke quit at rates 2-3 times greater than placebo. Currently in the U.S., varenicline is not available over the counter (OTC). In this study, we assessed the safety and efficacy of 1mg and 0.5mg varenicline as an OTC medication for smoking cessation in comparison to placebo., Methods: This randomized, double-blind, placebo-controlled study was performed at two clinical sites in the United States of n=313 people. The treatment period was 12 weeks. During the COVID pandemic, the protocol was modified to allow remote participation; verification of smoking status was via breath carbon monoxide levels for in-person visits and mailed urine cotinine kits for the remote participants., Results: There was no difference in biologically confirmed continuous abstinence by condition between Weeks 8-12; however, the odds of biologically confirmed point prevalence abstinence were higher for those in the 1mg b.i.d. condition than for those in the placebo condition at Week 12 (OR 3.39; 95% CI 1.49, 7.71), and were higher for those assigned to the 1.0mg b.i.d. condition than the 0.5mg b.i.d. condition at Week 12 (OR 2.37; 95% CI 1.11, 5.05). Adverse events were modest, and as expected (vivid dreams and nausea in the medication conditions)., Conclusions: The results are suggestive that varenicline is safe and effective as an OTC medication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The aim of this study was to compare past 12-month use of cigarette smoking cessation aids (e.g., Food and Drug Administration (FDA)-approved cessation products or e-cigarettes for smoking cessation) among people with substance use problems (PWSUPs) who currently smoke to people without substance use problems (SUPs) who currently smoke cigarettes in a nationally representative US sample., Methods: We used the Population Assessment of Tobacco and Health (PATH) Wave 6 Study [n = 30,516]. Our sample comprised adult (18+) established cigarette smokers (100+ lifetime-sticks with daily/non-daily use) [n = 5,895]. The independent variable was SUP status (no, moderate, and high). The dependent variables were past-year use of: nicotine replacement therapies (NRTs), cessation medications [i.e., varenicline or bupropion], or e-cigarettes [for cigarette cessation and reduction]. Weighted multivariable logistic regression models for each dependent variable examined the associations between SUP status and each cessation aid, adjusting for cigarette dependence, daily cigarette smoking, and demographic factors., Results: Among people who smoke, a higher proportion of respondents with high SUP severity used NRTs, cessation medications, and e-cigarettes for cigarette cessation, respectively (12.3%, 8.4%, 15.7%), compared to those with no/low SUP severity (9.8%, 6.0%, 8.9%). In the multivariable models, respondents with high SUPs had 63% (95% CI:1.16-2.29) higher odds of using e-cigarettes for cessation than those without SUPs. No significant differences were seen between high (vs. no/low SUPs) in the past-year use of NRTs and cessation medications., Conclusion: Our findings indicate that cigarette smokers with high SUPs had higher odds of using e-cigarettes for cessation and reduction compared to smokers without SUPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Terms such as 'natural', 'organic' and 'tobacco and water' on cigarette packs may communicate misleading reduced harm messages to consumers. This study describes sales volume and price for brands that used these misleading descriptors in the USA by year, brand and state., Methods: The data come from Information Resources Incorporated sales data collected in 44 US states from January 2018 to January 2023. Trained coders used Universal Product Codes, purchased packs and internet searches to identify cigarettes sold with 'natural', 'organic' and 'tobacco and water' on packs. We report cigarette pack unit sales counts (sales volume) and average price per pack by year, as well as per cent year-over-year change in sales volume and price and annual market share by descriptor terms., Results: Overall, pack sales volume decreased year-over-year from 2019 to 2022. Sales volume for packs with 'natural', 'tobacco and water' and 'organic' decreased less than overall; in some cases, they increased. In 2022, packs with 'natural' accounted for the greatest share of cigarette unit sales (5.42% or 33 605 036 packs), followed by 'tobacco and water' (2.25% or 12 959 905 packs) and 'organic' (0.53% or 4 614 592 packs). Natural American Spirit (NAS) and Winston accounted for most sales with 'natural' and 'tobacco and water'; NAS accounted for nearly all sales with 'organic'. Packs with 'natural', 'tobacco and water' or 'organic' made up the largest portion of sales in western (Oregon, Idaho, California, Colorado and Washington) and northeastern (Vermont, Massachusetts and New Hampshire) US states., Conclusion: Brands using 'natural', 'tobacco and water' and 'organic' on packs increased their market share between 2019 and 2022; in some states, market share was over 10% in 2022. Our findings emphasise the importance of regulating these terms and continually monitoring their population impact., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Globally, the COVID-19 pandemic upended healthcare services and created economic vulnerability for many. Criminalization of sex work meant sex workers were largely ineligible for Canada's government-based financial pandemic relief, the Canadian Emergency Response Benefit. Sex workers' loss of income and inability to access financial support services during the pandemic resulted in many unable to pay rent or mortgage, and in need of assistance with basic needs items including food. Little is known about the unique experiences of sex workers who faced challenges in accessing food during the pandemic and its impact on healthcare access. Thus, we aimed to identify the association between pandemic-related challenges accessing food and primary healthcare among sex workers., Methods: Prospective data were drawn from a cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers' Health Access, AESHA; 2010-present). Data were collected via questionnaires administered bi-annually from October 2020-August 2021. We used univariate and multivariable logistic regression with generalized estimating equations to assess the association between pandemic-related challenges accessing food and challenges accessing primary healthcare over the study period., Results: Of 170 participants, 41% experienced pandemic-related challenges in accessing food and 26% reported challenges accessing healthcare. Median age was 45 years (IQR:36-53), 56% were of Indigenous ancestry, 86% experienced intimate partner violence in the last six months, and 62% reported non-injection substance use in the last six months. Experiencing pandemic-related challenges accessing food was positively associated with challenges accessing primary healthcare (Adjusted Odds Ratio: 1.99, 95% Confidence Interval: 1.02-3.88) after adjustment for confounders., Conclusions: Findings provide insight about the potential role community-based healthcare delivery settings (e.g., community clinics) can play in ameliorating access to basic needs such as food among those who are highly marginalized. Future pandemic response efforts should also take the most marginalized populations' needs into consideration by establishing strategies to ensure continuity of essential services providing food and other basic needs. Lastly, policies are needed establishing basic income support and improve access to food resources for marginalized women in times of crisis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A factor constraining the elimination of dog-mediated human rabies is limited information on the size and spatial distribution of free-roaming dog populations (FRDPs). The aim of this study was to develop a statistical model to predict the size of free-roaming dog populations and the spatial distribution of free-roaming dogs in urban areas of Nepal, based on real-world dog census data from the Himalayan Animal Rescue Trust (HART) and Animal Nepal. Candidate explanatory variables included proximity to roads, building density, specific building types, human population density and normalised difference vegetation index (NDVI). A multivariable Poisson point process model was developed to estimate dog population size in four study locations in urban Nepal, with building density and distance from nearest retail food establishment or lodgings as explanatory variables. The proposed model accurately predicted, within a 95 % confidence interval, the surveyed FRDP size and spatial distribution for all four study locations. This model is proposed for further testing and refinement in other locations as a decision-support tool alongside observational dog population size estimates, to inform dog health and public health initiatives including rabies elimination efforts to support the 'zero by 30' global mission., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Former Associate Editor, Spatial and Spatio-temporal Epidemiology (Mark Stevenson), (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Breakfast is often cited as the most important meal of the day and vital for students' academic functioning at school. Although much research has linked students' breakfast consumption to better achievement, there has been debate about why and how breakfast has academic benefits. The present study of 648 Australian high school students investigated (a) the role of breakfast consumption and breakfast quality in students' self-reported motivation and their achievement in a science test, (b) the role of motivation in mediating the link between breakfast consumption and quality and students' achievement, and (c) the extent to which breakfast consumption effects are moderated by the quality of breakfast (e.g., more vegetables, fruit, dairy/protein, wholegrains, cereals, water; less sugary drinks, processed meat, fast take-away, unhealthy snack foods). Findings indicated that beyond the effects of personal, home, and classroom factors, breakfast consumption predicted higher adaptive motivation (p < .05), breakfast quality predicted lower maladaptive motivation (p < .05), and in turn, students' adaptive (positively, p < .01) and maladaptive (negatively, p < .01) motivation predicted their achievement. Moreover, adaptive motivation significantly mediated the relationship between breakfast consumption and achievement (p < .05). The effect of breakfast consumption was moderated by the quality of breakfast such that consuming a high-quality breakfast in the morning was associated with the highest levels of adaptive motivation (p < .01) and achievement (p < .05) later in the day. Findings have implications for educational practice and policy seeking to promote a healthy start to the school day to optimize students' motivation and achievement., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Intravenous administration of interleukin (IL)-31 in healthy dogs has been used as a model to assess antipruritic drugs. However, there is no known in-depth characterisation of pruritic behaviours, and the repeatability of the IL-31-induced pruritus in the individual dogs is currently unknown., Objectives: To evaluate the immediate/delayed pruritus responses and the pruritic behaviours observed in the IL-31-induced pruritic model in healthy dogs after repeated IL-31 injections., Animals: Fifteen healthy laboratory beagles., Methods: All dogs were video-recorded for 270 min after two intravenous recombinant IL-31 injections (1.75 μg/kg) and vehicle (phosphate-buffered saline, control) injections, respectively; interventions were randomised and performed with a 2 week wash-out period. Two blinded investigators reviewed the pruritic behaviours of all video recordings., Results: Both canine IL-31 (IL-31&#95;01, IL-31&#95;02) injections significantly increased pruritic seconds and categorical minutes ('YES'/'NO' behaviour per discrete 1 min interval) in healthy dogs compared with both vehicle groups (Vehicle&#95;01, Vehicle&#95;02). The second intravenous canine IL-31 (IL-31&#95;02) administered 14 days after the first IL-31 injection induced a significant increase in pruritic seconds (p = 0.021) and not pruritic categorical minutes (p = 0.231). An increase in pruritic seconds was observed in both IL-31 groups in the first 30 min post-administration, while there was no significant difference between IL-31 and vehicle groups., Conclusions and Clinical Relevance: In conclusion, intravenous IL-31 reproducibly induces itch responses in dogs. Future evaluations of the canine IL-31 pruritic model should assess total pruritic behaviours in seconds rather than using a biased 'YES/NO' behaviour per 1 min scoring system., (© 2023 ESVD and ACVD.)

Introduction: Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however, there is limited guidance for clinicians to follow regarding the most appropriate management options. The objective of this scoping review is to understand and map the extent of evidence in relation to the factors that relate to the outcome of non-pharmacological interventions on MSK condition-related fatigue across the lifespan., Methods and Analysis: This scoping review will include evidence relating to people of all ages living with chronic MSK conditions who have been offered a non-pharmacological intervention with either the intention or effect of reducing fatigue and its impact. Databases including AMED, PsycINFO, CINAHLPlus, MEDLINE, EMBASE and Scopus will be searched for peer-reviewed primary research studies published after 1 January 2007 in English language. These findings will be used to identify factors associated with successful interventions and to map gaps in knowledge., Ethics and Dissemination: Ethical approval was not required for this review. Findings will be disseminated by journal publications, conference presentations and by communicating with relevant healthcare and charity organisations., Competing Interests: Competing interests: PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this project. There are no competing interests in this project., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Mental rotation tasks are frequently used as standard measures of mental imagery. However, aphantasia research has brought such use into question. Here, we assessed a large group of individuals who lack visual imagery (aphantasia) on two mental rotation tasks: a three-dimensional block-shape, and a human manikin rotation task. In both tasks, those with aphantasia had slower, but more accurate responses than controls. Both groups demonstrated classic linear increases in response time and error-rate as functions of angular disparity. In the three-dimensional block-shape rotation task, a within-group speed-accuracy trade-off was found in controls, whereas faster individuals in the aphantasia group were also more accurate. Control participants generally favoured using object-based mental rotation strategies, whereas those with aphantasia favoured analytic strategies. These results suggest that visual imagery is not crucial for successful performance in classical mental rotation tasks, as alternative strategies can be effectively utilised in the absence of holistic mental representations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Māori., Methods: Crude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000-2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040., Results: Between 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10 - 80 ) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50-79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Māori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Māori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Māori)., Conclusion: The age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Māori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Māori. However, with the ageing of the population in Aotearoa New Zealand, and for Māori, CRC in the elderly will continue to dominate case numbers., (© 2024. The Author(s).)

The inability to visualise was given the name aphantasia in 2015 by Zeman and colleagues. In 2018 we published research showing that fifteen individuals who self-identified as having aphantasia also demonstrated a lack of sensory visual imagery when undergoing the binocular rivalry imagery paradigm, suggesting more than just a metacognitive difference. Here we update these findings with over fifty participants with aphantasia and show that there is evidence for a lack of sensory imagery in aphantasia. How the binocular rivalry paradigm scores relate to the vividness of visual imagery questionnaire (VVIQ) and how aphantasia can be confirmed is discussed., (Copyright © 2024. Published by Elsevier B.V.)

Cognitive neuroscience research on mental imagery has largely focused on the visual imagery modality in unimodal task contexts. Recent studies have uncovered striking individual differences in visual imagery capacity, with some individuals reporting a subjective absence of conscious visual imagery ability altogether ("aphantasia"). However, naturalistic mental imagery is often multi-sensory, and preliminary findings suggest that many individuals with aphantasia also report a subjective lack of mental imagery in other sensory domains (such as auditory or olfactory imagery). In this paper, we perform a series of cluster analyses on the multi-sensory imagery questionnaire scores of two large groups of aphantasic subjects, defining latent sub-groups in this sample population. We demonstrate that aphantasia is a heterogenous phenomenon characterised by dominant sub-groups of individuals with visual aphantasia (those who report selective visual imagery absence) and multi-sensory aphantasia (those who report an inability to generate conscious mental imagery in any sensory modality). We replicate our findings in a second large sample and show that more unique aphantasia sub-types also exist, such as individuals with selectively preserved mental imagery in only one sensory modality (e.g. intact auditory imagery). We outline the implications of our findings for network theories of mental imagery, discussing how unique aphantasia aetiologies with distinct self-report patterns might reveal alterations to various levels of the sensory processing hierarchy implicated in mental imagery., Competing Interests: Declaration of Interests The author(s) declared that there were no conflicts of interest with respect to the authorship or the publication of this article., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

An experimental study was conducted on how polymer density affects the transport and fate of microplastics in aquatic flows. For the first time, polypropylene (PP), polyethylene (PE), polymethyl methacrylate (PMMA), polyetheretherketone (PEEK), and polyvinyl chloride (PVC) were chemically stained and tested using solute transport techniques and velocities found among rivers in the natural environment (0.016 - 0.361 m/s). The movement of 3D-polymers with densities ranging from 0.9 - 1.4 g/cm³ was quantified in a laboratory flume scaled to simulate open-channel flows in fluvial systems. Except for PP, in most conditions microplastics exhibited similar transport characteristics to solutes regardless of density and established solute transport models were successfully implemented to predict their transport and fate. Mass recoveries and ADE routing model demonstrated microplastic deposition and resuspension was associated with polymer density below critical velocity thresholds ≤ 0.1 m/s. When density becomes the dominant force at these slower velocities, concentrations of denser than water microplastics will be momentarily or permanently deposited in channel beds and microplastics follow the classical Shields sediment transport methodology. This data is the first to provide microplastic suspension and deposition thresholds based on river velocity and polymer density, making a key contribution to research predicting microplastic fate and organismal exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigated whether reducing face skin temperature alters arterial blood pressure control and lower body negative pressure (LBNP) tolerance after exercise heat stress. Eight subjects (1 female; age, 27 ± 9 yr) exercised at ∼63% V̇o 2max until core temperature had increased ∼1.5°C before undergoing LBNP to presyncope either with fanning to return face skin temperature to baseline (Δ-5°C, Fan trial) or without (No Fan trial). LBNP tolerance was quantified as cumulative stress index (CSI; mmHg·min). Before LBNP, whole body and face skin temperatures were elevated from baseline in both trials (38.0 ± 0.5°C and 36.3 ± 0.5°C, respectively, both P < 0.001). During LBNP, face skin temperature decreased in the Fan trial (30.9 ± 1.0°C) but was unchanged in the No Fan trial (36.1 ± 0.6°C, between trials P < 0.001). Mean arterial pressure was not different between trials ( P = 0.237) and was similarly reduced at presyncope in both trials (from 82 ± 7 to 67 ± 8 mmHg, P < 0.001). During LBNP, heart rate was attenuated in the Fan trial at Mid LBNP (146 ± 16 vs. 158 ± 12 beats/min, P = 0.036) and at peak heart rate (158 ± 15 vs. 170 ± 15 beats/min; P < 0.001). LBNP tolerance was not different between trials (321 ± 248 vs. 328 ± 115 mmHg·min, P = 0.851). In exercise heat-stressed individuals, lowering face skin temperature to normothermic values suppressed heart rate thereby altering cardiovascular control during a simulated hemorrhagic challenge without reducing tolerance.

Background: Substance use is a complex condition with multidimensional determinants. The present study aims to find the prevalence and determinants of substance use among young people attending primary healthcare centers in India., Methods: A multicentric cross-sectional study was conducted across 15 states in India on 1,630 young people (10-24 years) attending primary health centers. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to capture data on substance use. The degree of substance involvement was assessed and multivariate regression analysis was conducted to determine the risk factors of substance use., Results: The prevalence of substance use was 32.8%, with a median substance initiation age of 18 years. Among the substance users, 75.5% began before completing adolescence. Tobacco (26.4%), alcohol (26.1%) and cannabis (9.5%) were commonly consumed. Sociodemographic determinants included higher age, male gender, urban residence, positive family history, northeastern state residence and lower socioeconomic class. Over 80% of users had moderate or high involvement., Conclusions: High substance use prevalence among young people in Indian healthcare centers underscores the urgency of targeted intervention. Insights on determinants guide effective prevention strategies for this complex public health issue., Competing Interests: The authors declare none., (© The Author(s) 2024.)

Background: Suicide rates for children and adolescents have been increasing over the past 2 decades. In April 2023, the National Institute of Mental Health (NIMH) convened a two-day workshop to address child and youth suicide., Purpose: The workshop focus was to discuss the state of the science and stimulate a collaborative response between researchers, death investigators, and data collection teams to build a science to service and service to science approach toward understanding - and ultimately preventing - this growing problem of child and youth suicide., Highlights: Topics that meeting participants highlighted as worthy of further consideration for research and practice were: increasing awareness among death investigators, medical examiners, and coroners that child suicide deaths under age 10 years do occur and should be investigated and documented accordingly; emphasizing the value of science based protocols for child and youth death investigations to enhance consistency of approaches; and articulating needs for postvention services to suicide loss survivors., Outcomes: The importance of collecting an accurate and complete cause and manner of death (i.e., unintentional, suicide, homicide, undetermined) among all child decedents, and demographic information such as race, ethnicity, and sexual/gender minority status was underscored as critical for enhanced surveillance. For prevention efforts, approaches to assessing and understanding suicidal thoughts and behaviors among diverse groups of children, and the variability in proximal and distal risk factors are needed to inform opportunities for preventive interventions for diverse communities. The need for consistent measures and processes to improve death investigations, fatality review committees, and coordination between data collection systems and agencies was also raised., Practical Applications: Collaborations among researchers, death investigators, and data collection teams can help to fully describe the child and youth suicide crisis and provide actionable information for new research, and prevention and response efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Parent-child interactions are a critical pathway to emotion socialization, with disruption to these processes associated with risk for childhood behavior problems. Using computational linguistics methods, we tested whether (1) play context influenced parent-child socioemotional language, and (2) child conduct problems or callous-unemotional traits were associated with patterns of socioemotional or nonsocial language across contexts. Seventy-nine parent-child dyads (children, 5-6 years old) played a socioemotional skills ("social context") or math ("nonsocial context") game at home. We transcribed and analyzed game play, which had been audio recorded by participants. The social context elicited more socioemotional and cognitive words, while the nonsocial context elicited more mathematical words. The use of socioemotional language by parents and children was more strongly correlated in the social context, but context did not moderate the degree of correlation in cognitive or mathematical word use between parents and children. Children with more conduct problems used fewer socioemotional words in the social context, while children with higher callous-unemotional traits used fewer cognitive words in both contexts. We highlight the role of context in supporting socioemotionally rich parent-child language interactions and provide preliminary evidence for the existence of linguistic markers of child behavior problems. Our results also inform naturalistic assessments of parent-child interactions and home-based interventions for parents and children facing socioemotional or behavioral challenges., (© 2024. The Author(s).)

Our study proposes to examine how stress and emotion recognition interact with a history of maltreatment to influence sensitive parenting behaviors. A sample of 58 mothers and their children aged between 2 and 5 years old were recruited. Parents' history of maltreatment was measured using the Child Trauma Questionnaire. An emotion recognition task was performed. Mothers identified the dominant emotion in morphed facial emotion expressions in children. Mothers and children interacted for 15 minutes. Salivary cortisol levels of mothers were collected before and after the interaction. Maternal sensitive behaviors were coded during the interaction using the Coding Interactive Behavior scheme. Results indicate that the severity of childhood maltreatment is related to less sensitive behaviors for mothers with average to good abilities in emotion recognition and lower to average increases in cortisol levels following an interaction with their children. For mothers with higher cortisol levels, there is no association between a history of maltreatment and sensitive behaviors, indicating that higher stress reactivity could act as a protective factor. Our study highlights the complex interaction between individual characteristics and environmental factors when it comes to parenting. These results argue for targeted interventions that address personal trauma.

Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (β-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Throughout the COVID-19 pandemic, an unprecedented level of clinical nasal swab data from around the globe has been collected and shared. Positive tests have consistently revealed viral titers spanning six orders of magnitude! An open question is whether such extreme population heterogeneity is unique to SARS-CoV-2 or possibly generic to viral respiratory infections. To probe this question, we turn to the computational modeling of nasal tract infections. Employing a physiologically faithful, spatially resolved, stochastic model of respiratory tract infection, we explore the statistical distribution of human nasal infections in the immediate 48 h of infection. The spread, or heterogeneity, of the distribution derives from variations in factors within the model that are unique to the infected host, infectious variant, and timing of the test. Hypothetical factors include: (1) reported physiological differences between infected individuals (nasal mucus thickness and clearance velocity); (2) differences in the kinetics of infection, replication, and shedding of viral RNA copies arising from the unique interactions between the host and viral variant; and (3) differences in the time between initial cell infection and the clinical test. Since positive clinical tests are often pre-symptomatic and independent of prior infection or vaccination status, in the model we assume immune evasion throughout the immediate 48 h of infection. Model simulations generate the mean statistical outcomes of total shed viral load and infected cells throughout 48 h for each "virtual individual", which we define as each fixed set of model parameters (1) and (2) above. The "virtual population" and the statistical distribution of outcomes over the population are defined by collecting clinically and experimentally guided ranges for the full set of model parameters (1) and (2). This establishes a model-generated "virtual population database" of nasal viral titers throughout the initial 48 h of infection of every individual, which we then compare with clinical swab test data. Support for model efficacy comes from the sampling of infection dynamics over the virtual population database, which reproduces the six-order-of-magnitude clinical population heterogeneity. However, the goal of this study is to answer a deeper biological and clinical question. What is the impact on the dynamics of early nasal infection due to each individual physiological feature or virus-cell kinetic mechanism? To answer this question, global data analysis methods are applied to the virtual population database that sample across the entire database and de-correlate (i.e., isolate) the dynamic infection outcome sensitivities of each model parameter. These methods predict the dominant, indeed exponential, driver of population heterogeneity in dynamic infection outcomes is the latency time of infected cells (from the moment of infection until onset of viral RNA shedding). The shedding rate of the viral RNA of infected cells in the shedding phase is a strong, but not exponential, driver of infection. Furthermore, the unknown timing of the nasal swab test relative to the onset of infection is an equally dominant contributor to extreme population heterogeneity in clinical test data since infectious viral loads grow from undetectable levels to more than six orders of magnitude within 48 h.

Background: Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd., Patients and Methods: Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded., Results: Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred., Conclusion: In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration., Competing Interests: Disclosure CP reports grant funding support: Pfizer, Daiichi Sankyo, Exact Sciences, Gilead and Seagen. Honoraria for advisory boards: Pfizer, Roche, Daiichi Sankyo, Novartis, Exact Sciences, Gilead, SeaGen and Eli Lilly. Support for travel and conferences: Roche, Novartis and Gilead. All other authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is caused by a trinucleotide CAG repeat expansion in the HTT gene that codes for the protein huntingtin (HTT in humans or Htt in mice). HTT is a multi-functional, ubiquitously expressed protein that is essential for embryonic survival, normal neurodevelopment, and adult brain function. The ability of wild-type HTT to protect neurons against various forms of death raises the possibility that loss of normal HTT function may worsen disease progression in HD. Huntingtin-lowering therapeutics are being evaluated in clinical trials for HD, but concerns have been raised that decreasing wild-type HTT levels may have adverse effects. Here we show that Htt levels modulate the occurrence of an idiopathic seizure disorder that spontaneously occurs in approximately 28% of FVB/N mice, which we have called FVB/N Seizure Disorder with SUDEP (FSDS). These abnormal FVB/N mice demonstrate the cardinal features of mouse models of epilepsy including spontaneous seizures, astrocytosis, neuronal hypertrophy, upregulation of brain-derived neurotrophic factor (BDNF), and sudden seizure-related death. Interestingly, mice heterozygous for the targeted inactivation of Htt (Htt+/- mice) exhibit an increased frequency of this disorder (71% FSDS phenotype), while over-expression of either full length wild-type HTT in YAC18 mice or full length mutant HTT in YAC128 mice completely prevents it (0% FSDS phenotype). Examination of the mechanism underlying huntingtin's ability to modulate the frequency of this seizure disorder indicated that over-expression of full length HTT can promote neuronal survival following seizures. Overall, our results demonstrate a protective role for huntingtin in this form of epilepsy and provide a plausible explanation for the observation of seizures in the juvenile form of HD, Lopes-Maciel-Rodan syndrome, and Wolf-Hirschhorn syndrome. Adverse effects caused by decreasing huntingtin levels have ramifications for huntingtin-lowering therapies that are being developed to treat HD.

The transport of microplastics within urban water systems remains poorly understood, with little prior research on their behaviour within manhole configurations. This study represents the first to measure and model the transport dynamics of microplastics within circular and square manholes under different hydraulic scenarios. The transport and fate of polyethylene (PE) was quantified and compared to solutes (Rhodamine WT dye) using energy losses, residence time distributions (RTDs), and mixing models within surcharging and overflowing manholes. The bulk mass of solute and PE concentrations followed similar flow paths across all conditions except for 17.3 ± 7.9 % of PE mass that was immobilized in a dead zone above the inlet pipe for manholes with a surcharge to pipe diameter ratio ≥2. Consequently, these microplastics only exit after a significant change in hydraulic regime occurs, causing microplastics to be at risk of being contaminated over a prolonged duration. No significant mixing differences for PE and solutes were found between manhole geometries. The deconvolution method outperformed the ADZ model with goodness of fit (R t 2 ) values of 0.99 (0.60) and 1.00 (0.89) for PE and solute mixing, respectively. This establishes the deconvolution method as the most accurate and appropriate model to accurately predict microplastic mixing in manholes and urban drainage systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent research suggests imagery is functionally equivalent to a weak form of visual perception. Here we report evidence across five independent experiments on adults that perception and imagery are supported by fundamentally different mechanisms: Whereas perceptual representations are largely formed via increases in excitatory activity, imagery representations are largely supported by modulating nonimagined content. We developed two behavioral techniques that allowed us to first put the visual system into a state of adaptation and then probe the additivity of perception and imagery. If imagery drives similar excitatory visual activity to perception, pairing imagery with perceptual adapters should increase the state of adaptation. Whereas pairing weak perception with adapters increased measures of adaptation, pairing imagery reversed their effects. Further experiments demonstrated that these nonadditive effects were due to imagery weakening representations of nonimagined content. Together these data provide empirical evidence that the brain uses categorically different mechanisms to represent imagery and perception.

This article presents a case study where integration of arts and humanities into a clinical programme is being implemented at scale, as core mandatory learning for all students within a UK dental, undergraduate context. The cross-disciplinary programme described, that integrates the Humanities with Clinical Sciences, is a longitudinal professional identity formation curriculum for sustainable oral healthcare which aligns with the UK dental regulator's proposals for a 'safe practitioner' framework for new graduates. The Clinical Humanities & Wellbeing modules embrace the emotional and attitudinal aspects of learning and educate clinical students for the practical wisdom (phronesis) required to deliver 21st century oral healthcare in an era of uncertainty. The overarching aim of the curriculum and its accompanying assessment is to promote critical reflection, student insight and development of integrity, reflexivity, and responsibility. Enabling the subjectification of professional identity formation in this cross-disciplinary way aims to develop students as 'safe practitioners', with increased professional autonomy, responsible for their own actions, and who are better equipped for the uncertainties and phronesis of clinical practice. At present, the programme is being evaluated, employing illuminative evaluation methodology and we present some tentative initial findings. The authors believe that this unique approach and signature pedagogy is, with careful curation, transferrable to other health professions' contexts.

Background: Establishing and maintaining relationships and ways of connecting and being with others is an important component of health and wellbeing. Harnessing the relational within caring, supportive, educational, or carceral settings as a systems response has been referred to as relational practice. Practitioners, people with lived experience, academics and policy makers, do not yet share a well-defined common understanding of relational practice. Consequently, there is potential for interdisciplinary and interagency miscommunication, as well as the risk of policy and practice being increasingly disconnected. Comprehensive reviews are needed to support the development of a coherent shared understanding of relational practice., Method: This study uses a scoping review design providing a scope and synthesis of extant literature relating to relational practice focussing on organisational and systemic practice. The review aimed to map how relational practice is used, defined and understood across health, criminal justice, education and social work, noting any impacts and benefits reported. Searches were conducted on 8 bibliographic databases on 27 October 2021. English language articles were included that involve/discuss practice and/or intervention/s that prioritise interpersonal relationships in service provision, in both external (organisational contexts) and internal (how this is received by workers and service users) aspects., Results: A total of 8010 relevant articles were identified, of which 158 met the eligibility criteria and were included in the synthesis. Most were opinion-based or theoretical argument papers (n = 61, 38.60%), with 6 (3.80%) critical or narrative reviews. A further 27 (17.09%) were categorised as case studies, focussing on explaining relational practice being used in an organisation or a specific intervention and its components, rather than conducting an evaluation or examination of the effectiveness of the service, with only 11 including any empirical data. Of the included empirical studies, 45 were qualitative, 6 were quantitative, and 9 mixed methods studies. There were differences in the use of terminology and definitions of relational practice within and across sectors., Conclusion: Although there may be implicit knowledge of what relational practice is the research field lacks coherent and comprehensive models. Despite definitional ambiguities, a number of benefits are attributed to relational practices., Systematic Review Registration: PROSPERO CRD42021295958., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection has represented a global challenge. Intriguingly, it has been shown that the alveolar lung epithelium expresses little Angiotensin Converting Enzyme receptor protein (ACE2), the entry receptor for SARS-CoV-2. Upper airway establishment of infection and translocation to the lung is well documented but other anatomical niches may be relevant to potentially serious lung infection. ACE2 is heavily expressed in the gastrointestinal tract and gastrointestinal symptoms support a clinical diagnosis of Coronavirus disease 2019 (COVID-19). This suggests a research question and the need to gather patient data exploring potential aerodigestive links in SARS-CoV-2 tranlocation and infection which may be relevant in the peripheral lung. This recognizes anatomical proximity and concepts of bi-directional movement between the Gastrointestinal and lung systems in normal physiology and disease. We have therefore explored the potential for gastro oesophageal reflux disease (GORD) micro aspiration and aeorodigestive pathophysiology in a novel prospective investigation of patients hospitalized with COVID-19., Methods: This is a prospective descriptive cohort study of 210 patients who were hospitalized with a confirmed diagnosis of COVID-19. The cohort was divided into three groups of patients based on symptom severity and radiological results. The Reflux Symptom Index (RSI) was used to evaluate the presence and severity of GOR. An RSI greater than 13 is considered to be abnormal. Patients' saliva samples were tested using enzyme-linked immunosorbent assay (ELISA) to determine the level of salivary pepsin among the cohort of patients., Results: A total of 210 patients with COVID-19 were enrolled in the study with 55.2% (116/210) classified as mildly ill, 31.9% (67/210) moderately ill and 12.9% (27/210) as severely ill. 34% (72/210) of the patients had an RSI score of over 13 and a median salivary pepsin value of 54 ± 29 ng/ml which suggested an incidence of extraesophageal reflux (EOR) in around a third of patients. The presence of respiratory comorbid conditions, an RSI score of over 13 and a salivary pepsin level of > 76ng/ml increased the risk of developing a more severe COVID-19 infection., Conclusion: The study showed a high prevalence of EOR among the study cohort and provide the first prospective evidence suggesting the potential for aerodigestive pathophysiology including microaspiration in COVID-19 disease. We believe that the results of our study support the need for more extensive research., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins. Based on converging evidence, one possibility is that they stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABA A )-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used over the left M1 to evaluate intracortical facilitation (ICF) and short intracortical inhibition (SICI), indirect assays of GLUTergic activity and GABA A -mediated inhibition, in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. Behaviourally, rewards and punishments enhanced both reaction and movement time. During movement preparation, regardless of rewards or punishments, ICF increased when the index finger initiated sequences, whereas SICI decreased when both the index and little fingers initiated sequences. This finding suggests that GLUTergic activity increases in a finger-specific manner whilst GABA A -mediated inhibition decreases in a finger-unspecific manner during preparation. In parallel, both rewards and punishments non-specifically increased ICF, but only rewards non-specifically decreased SICI as compared to neutral. This suggests that to enhance performance rewards both increase GLUTergic activity and decrease GABA A -mediated inhibition, whereas punishments selectively increase GLUTergic activity. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the intracortical excitability changes in M1 by which incentives enhance motor performance., Competing Interests: Declaration of competing interest This work was funded by the Fonds de Recherche du Québec – Nature et Technologie (Québec, Canada), European Research Council Starting Grant (MotMotLearn 637,488) and Proof of Concept Grant (ImpHandRehab 872,082). We wish to declare to Brain Stimulation that there is no financial/personal interest or belief that could affect the objectivity of the results wherein submitted. All authors agreed on the content of the manuscript prior to its submission to Brain Stimulation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Complex Regional Pain Syndrome (CRPS) is a disabling and distressing chronic pain condition characterised by a range of sensory, motor, autonomic and trophic symptoms. Guidelines recommend early referral for therapies that promote movement of the painful limb. However, evidence suggests a lack of defined therapy pathways for CRPS., Aims: The current study aims to explore CRPS therapy management in centres of excellence in England, and outside of these settings, to understand what facilitates and hinders best practice. The overall aim is to develop a draft stratified package of care to expedite patient access to optimal CRPS therapy across the management pathway., Methods and Analysis: Semi-structured interviews will be conducted with therapists working in CRPS centres of excellence and with therapists in other settings. Observations of therapy interventions in CRPS centres of excellence and interviews with patients who have received this care, will also help to identify potential key care package components. Interview data will be analysed using thematic analysis, mapped to the Theoretical Domains Framework (TDF), and Intervention Mapping Adapt (IMA) framework. Observations will be described and documented using the TDF headings., Conclusion: A triangulation protocol for qualitative health research will be used to integrate all data. Online stakeholder events will be held using consensus methods to agree a draft package of care for future implementation following further refinement, testing and evaluation., Clinical Trial Registration: The trial was registered with ISRCTN registry on 24 February 2022 (ISRCTN16917807)., (© 2023 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Introduction: People believe that cigarettes using 'organic,' 'additive-free' or similar descriptors are less harmful than other cigarettes. Natural American Spirit (NAS) is the most popular US cigarette brand using these descriptors. This cohort study describes changes in US smokers' odds of preferring NAS and changes in NAS smokers' odds of believing their brand might be less harmful than other brands., Methods: Data come from four waves (2013-2018) of the Population Assessment of Tobacco and Health (PATH) Study. Generalised estimating equations produced population-averaged estimates of relationships between (1) NAS brand preference and wave and (2) belief that one's own brand might be less harmful than other brands, wave and NAS brand preference. Models tested interactions by age group and sexual minority status., Results: The odds that smokers preferred NAS increased by 60% in W4 relative to W1. Disproportionate preference by younger adult and sexual minority smokers was observed. The odds that NAS smokers believed their own brand might be less harmful decreased by 50% between W1 and W4, but this perception was still 16 times higher for NAS compared with non-NAS smokers. Given the increasing preference for NAS, there was no significant change in the absolute number of NAS smokers who believed their own brand might be less harmful (W1: 562 122 (95% CI 435 190 to 689 055) vs W4: 580 378 (95% CI 441 069 to 719 689))., Conclusions: Both brand popularity and concentration of brand-related harm perceptions are important for understanding population impact of changes in cigarette marketing., Competing Interests: Competing interests: JP is a paid expert witness for the Plaintiffs in a Multi-District Litigation invoking American Spirit Cigarettes. This arrangement has been reviewed and approved by the University of Nevada, Reno in accordance with their conflicts of interest policies., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use., Methods: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1., Results: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups., Conclusions: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4., Impact: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status., (©2023 American Association for Cancer Research.)

Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response., (© 2023. Springer Nature Limited.)

Introduction: While previous research has examined misperceptions related to Natural American Spirit (NAS), a premium cigarette brand using 'natural'-themed marketing, the longitudinal relationship between NAS-related harm beliefs and switching to NAS has not been established., Methods: Using data from the PATH study, we modelled the longitudinal relationship between (1) brand switching and subsequent belief that one's own brand might be less harmful than other brands (Waves 1-5); (2) belief that organic and/or additive-free tobacco products are less harmful and subsequent brand switching (Waves 3-5); and (3) belief that some types of cigarettes are less harmful and subsequent brand switching (Waves 3-5) for NAS and two leading comparator brands (Camel and Marlboro)., Results: Among people who did not think their prior brand might be less harmful, switching to NAS or maintaining NAS preference increased the odds of believing one's own brand might be less harmful (aOR 19.4; 95% CI: 15.19, 24.8; aOR 6.1; 95% CI: 4.23, 8.67, respectively). Prior belief that organic and additive-free tobacco products were less harmful increased the odds of switching to (aOR 2.5; 95% CI: 1.68, 3.74) and decreased the odds of switching away (0.57; 955 CI: 0.36, 0.92) from NAS in the subsequent wave. Parallel analyses for Marlboro/Camel were largely null or in the opposite direction., Conclusions: NAS use may maintain or shape new beliefs that the brand may be less harmful than other brands; holding pre-existing beliefs about the relative harm of some tobacco products may increase risk for NAS use., Competing Interests: Competing interests: JP is a paid expert witness for the Plaintiffs in a Multi-District Litigation invoking Natural American Spirit Cigarettes and a paid expert witness for the Plaintiffs in Derivative Litigation invoking Altria Group, Inc. This arrangement has been reviewed and approved by the University of Nevada, Reno in accordance with their conflicts of interest policies., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a novel delithiation process for epitaxial thin films of LiCoO 2 (001) cathodes using only physical methods, based on ion sputtering and annealing cycles. Preferential Li sputtering followed by annealing produces a surface layer with a Li molar fraction in the range 0.5 < x < 1, characterized by good crystalline quality. This delithiation procedure allows the unambiguous identification of the effects of Li extraction without chemical byproducts and experimental complications caused by electrolyte interaction with the LiCoO 2 surface. An analysis by X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) provides a detailed description of the delithiation process and the role of O and Co atoms in charge compensation. We observe the simultaneous formation of Co 4+ ions and of holes localized near O atoms upon Li removal, while the surface shows a (2 × 1) reconstruction. The delithiation method described here can be applied to other crystalline battery elements and provide information on their properties that is otherwise difficult to obtain.