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Abstract We conducted a retrospective population-based, matched cohort study using the National Health Insurance Research Database to estimate healthcare resource utilisation (HRU) and costs in patients with newly diagnosed AL amyloidosis in Taiwan. Cases were matched 10:1 by age, sex, and area of residence to patients without AL amyloidosis (comparators) randomly selected from the database during the same time period. Annual all-cause HRU and costs for 3 years were quantified. AL amyloidosis-attributable costs were obtained by subtracting all-cause HRU costs incurred by comparators from cases. The mean age of all patients was 60.78 years and 59.07% were male. Co-morbidities were more frequent in cases than comparators. By 6 months after diagnosis, 12.1% of cases had died versus 0.9% of comparators. In the first year, cases had 103% more outpatient visits, 177% more emergency room visits, were hospitalised 4-times more frequently, and spent 5.5-times more days in hospital than comparators, and total healthcare costs were > sixfold higher. Costs incurred during the first year after diagnosis accounted for 55% of the 3-year cumulative cost. High HRU costs associated with delayed diagnosis and end-organ damage indicate a need for earlier diagnosis and more effective treatments for AL amyloidosis.

The effect of plasma-activated water (PAW) generated with a dielectric barrier discharge diffusor (DBDD) system on microbial load and organoleptic quality of cucamelons was investigated and compared to the established sanitizer, sodium hypochlorite (NaOCl). Pathogenic serotypes of Escherichia coli, Salmonella enterica, and Listeria monocytogenes were inoculated onto the surface of cucamelons (6.5 log CFU g-1) and into the wash water (6 log CFU mL-1). PAW treatment involved 2 min in situ with water activated at 1,500 Hz and 120 V and air as the feed gas; NaOCl treatment was a wash with 100 ppm total chlorine; control treatment was a wash with tap water. PAW treatment produced a 3-log CFU g-1 reduction of pathogens on the cucamelon surface without negatively impacting quality or shelf life. NaOCl treatment reduced the pathogenic bacteria on the cucamelon surface by 3 to 4 log CFU g-1; however, this treatment also reduced fruit shelf life and quality. Both systems reduced 6-log CFU mL-1 pathogens in the wash water to below detectable limits. The critical role of superoxide anion radical (·O2-) in the antimicrobial power of DBDD-PAW was demonstrated through a Tiron scavenger assay, and chemistry modeling confirmed that ·O2- generation readily occurs in DBDD-PAW generated with the employed settings. Modeling of the physical forces produced during plasma treatment showed that bacteria likely experience strong local electric fields and polarization. We hypothesize that these physical effects synergize with reactive chemical species to produce the acute antimicrobial activity seen with the in situ PAW system. IMPORTANCE Plasma-activated water (PAW) is an emerging sanitizer in the fresh food industry, where food safety must be achieved without a thermal kill step. Here, we demonstrate PAW generated in situ to be a competitive sanitizer technology, providing a significant reduction of pathogenic and spoilage microorganisms while maintaining the quality and shelf life of the produce item. Our experimental results are supported by modeling of the plasma chemistry and applied physical forces, which show that the system can generate highly reactive ·O2- and strong electric fields that combine to produce potent antimicrobial power. In situ PAW has promise in industrial applications as it requires only low power (12 W), tap water, and air. Moreover, it does not produce toxic by-products or hazardous effluent waste, making it a sustainable solution for fresh food safety.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. Methods We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction–associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. Results Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3–17.1) years of follow-up. Compared to an FLI

Abstract Cancers of Unknown Primary (CUP) remains a diagnostic and therapeutic challenge due to biological heterogeneity and poor responses to standard chemotherapy. Predicting tissue-of-origin (TOO) molecularly could help refine this diagnosis, with tissue acquisition barriers mitigated via liquid biopsies. However, TOO liquid biopsies are unexplored in CUP cohorts. Here we describe CUPiD, a machine learning classifier for accurate TOO predictions across 29 tumour classes using circulating cell-free DNA (cfDNA) methylation patterns. We tested CUPiD on 143 cfDNA samples from patients with 13 cancer types alongside 27 non-cancer controls, with overall sensitivity of 84.6% and TOO accuracy of 96.8%. In an additional cohort of 41 patients with CUP CUPiD predictions were made in 32/41 (78.0%) cases, with 88.5% of the predictions clinically consistent with a subsequent or suspected primary tumour diagnosis, when available (23/26 patients). Combining CUPiD with cfDNA mutation data demonstrated potential diagnosis re-classification and/or treatment change in this hard-to-treat cancer group.

Abstract The inhibition of action is a fundamental executive mechanism of human behaviour that involve a complex neural network. In spite of the progresses made so far, many questions regarding the brain dynamics occurring during action inhibition are still unsolved. Here, we used a novel approach optimized to investigate real-time effective brain dynamics, which combines transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recordings. 22 healthy volunteers performed a motor Go/NoGo task during TMS of the hand-hotspot of the primary motor cortex (M1) and whole-scalp EEG recordings. We reconstructed source-based real-time spatiotemporal dynamics of cortical activity and cortico-cortical connectivity throughout the task. Our results showed a task-dependent bi-directional change in theta/gamma supplementary motor cortex (SMA) and M1 connectivity that, when participants were instructed to inhibit their response, resulted in an increase of a specific TMS-evoked EEG potential (N100), likely due to a GABA-mediated inhibition. Interestingly, these changes were linearly related to reaction times, when participants were asked to produce a motor response. In addition, TMS perturbation revealed a task-dependent long-lasting modulation of SMA–M1 natural frequencies, i.e. alpha/beta activity. Some of these results are shared by animal models and shed new light on the physiological mechanisms of motor inhibition in humans.

BackgroundPatients who had a cryptogenic stroke (CS) suspected to be causally related to a patent foramen ovale (PFO) are candidates for percutaneous PFO closure. In such patients, it is important to screen for atrial fibrillation (AF). Limited guidance is available regarding AF monitoring strategies in CS patients with PFO addressing optimal monitoring technology and duration.AimTo provide a narrative review of cardiac rhythm monitoring in CS patients considered for PFO closure, including current practices, stroke recurrences after CS, findings from monitoring studies in CS patients, and predictors for AF detection published in the literature. To propose a personalized strategy for cardiac monitoring in CS patients, accounting for aspects predicting AF detection.Summary of reviewAF detection in CS patients is predicted by age, left atrial enlargement, prolonged PR interval, frequent premature atrial contractions, interatrial conduction block, diabetes, prior brain infarctions, leukoaraiosis, elevated B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and a family history of AF, as well as composed scores (e.g. CHA2DS2-VASc, atrial fibrillation in embolic stroke of undetermined source (AF-ESUS)). The causal role of the PFO may be accounted for by the risk of paradoxical embolism (RoPE) score and/or the PFO-Associated Stroke Causal Likelihood (PASCAL) classification.ConclusionA personalized approach to AF detection in CS patients is proposed, accounting for the likelihood of AF detection and aimed at obtaining sufficient confidence regarding the absence of AF in patients considered for PFO closure. In addition, the impact of high-risk PFO features on the monitoring strategy is discussed.

The alignment of technical and vocational education and training (TVET) with industry needs is pivotal for achieving sustainable development goals (SDGs) in Kenya. Yet, reliance on global commitment mechanisms, primarily voluntary national reviews (VNRs), has proven insufficient. This forum piece argues for a strategic transition towards voluntary local reviews (VLRs) and incorporating indigenous philosophies, such as Harambee, to better align TVET with SDG objectives. This transition is essential for fostering inclusive, equitable learning environments, enhancing workforce preparedness, and facilitating a community-centric educational model that effectively addresses local needs while contributing to global sustainability goals. Additionally, this forum piece underscores the need for institutional social change to resolve contradictions in current policies that hinder educational systems from reaching their goals. Drawing from a comparative study of TVET governance models in Nairobi, Kenya, and Pittsburgh, USA, this forum piece illustrates how different approaches can align TVET systems with localized educational demands and SDG frameworks, highlighting policy innovation, leadership development, and community engagement as key strategies for redefining TVET leadership.

Objectives The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA).Design and setting The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study.Participants From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort).Outcomes Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model.Results Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080).Conclusion In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Background: This study, using real-world data, assesses the impact of RS testing on treatment pathways and the associated economic consequences of such testing. This paper pertains to lobular breast cancer. Methods: A retrospective, observational study was undertaken between 2011 and 2019 on a cross-section of hormone receptor-positive (HR+), HER2-negative, lymph node-negative, early-stage breast cancer patients. All patients had ILC and had RS testing in Ireland. The patient population is representative of the national population. Patients were classified as low (RS ≤ 25) or high (RS > 25) risk. Patients aged ≤50 were stratified as low (RS 0–15), intermediate (RS 16–25), or high risk (RS > 25). Results: A total of 168 patients were included, most of whom had grade 2 (G2) tumors (n = 154, 92%). Overall, 155 patients (92.3%) had low RS (≤25), 12 (7.1%) had high RS (>25), and 1 (0.6%) had unknown RS status. In 29 (17.5%) patients aged ≤50 at diagnosis, RS was ≤15 in 16 (55%), 16–20 in 6 (21%), 21–25 in 5 (17%), >25 in 1 (3.5%), and unknown in 1 (3.5%). Post RS testing, 126 patients (78%) had a change in chemotherapy recommendation; all to hormone therapy. In total, only 35 patients (22%) received chemotherapy. RS testing achieved a 75% reduction in chemotherapy use, resulting in savings of €921,543.84 in treatment costs, and net savings of €387,283.84. Conclusions: The use of this test resulted in a 75% reduction in chemotherapy and a significant cost savings in our publicly funded health system.

RESUMO Embora os governos das economias de mercado avançadas estejam há muitos anos envolvidos na formulação de políticas destinadas a estimular o avanço científico e a mudança tecnológica, foi somente em meados da década de 1970 que políticas explícitas de “inovação” surgiram. A política de inovação representou uma integração das mais tradicionais “política industrial” e “política de ciência e tecnologia”. Durante o início da década de 1980, a ênfase das políticas públicas mais uma vez mudou quando os governos começaram a introduzir as chamadas “políticas de tecnologia”. A política de tecnologia envolve a seleção e o desenvolvimento de tecnologias genéricas específicas ou grupos de produtos de alta tecnologia. Hoje, todas as economias europeias avançadas adotaram políticas tecnológicas para apoiar a tecnologia da informação e a biotecnologia. Este artigo discute e compara as políticas de tecnologia no Reino Unido, na França e na República Federal da Alemanha, bem como as políticas que operam no nível europeu promulgadas pela EEC.

Abstract Governments around the world attempted to suppress the spread of COVID-19 using restrictions on social and economic activity. This study presents the first global analysis of job and income losses associated with those restrictions, using Gallup World Poll data from 321,000 randomly selected adults in 117 countries from July 2020 to March 2021. Nearly half of the world’s adult population lost income because of COVID-19, according to our estimates, and this outcome and related measures of economic harm—such as income loss—are strongly associated with lower subjective well-being, financial hardship, and self-reported loss of subjective well-being. Our primary analysis uses a multilevel model with country and month-year levels, so we can simultaneously test for significant associations between both individual demographic predictors of harm and time-varying country-level predictors. We find that an increase of one-standard deviation in policy stringency, averaged up to the time of the survey date, predicts a 0.37 std increase in an index of economic harm (95% CI 0.24–0.51) and a 14.2 percentage point (95% CI 8.3–20.1 ppt) increase in the share of workers experiencing job loss. Similar effect sizes are found comparing stringency levels between top and bottom-quintile countries. Workers with lower-socioeconomic status—measured by within-country income rank or education—were much more likely to report harm linked to the pandemic than those with tertiary education or relatively high incomes. The gradient between harm and stringency is much steeper for workers at the bottom quintiles of the household income distribution than it is for those at the top, which we show with interaction models. Socioeconomic status is unrelated to harm where stringency is low, but highly and negatively associated with harm where it is high. Our detailed policy analysis reveals that school closings, stay-at-home orders, and other economic restrictions were strongly associated with economic harm, but other non-pharmaceutical interventions—such as contact tracing, mass testing, and protections for the elderly were not.

The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal synchrony, and biological synchrony. The construct validity of positivity resonance and its longitudinal associations with health have not been tested. The current longitudinal study examined whether positivity resonance in conflict interactions between 154 married couples predicts health trajectories over 13 years and longevity over 30 years. We used couples' continuous ratings of affect during the interactions to capture coexperienced positive affect and continuous physiological responses to capture biological synchrony between spouses. Video recordings were behaviorally coded for coexpressed positive affect, synchronous nonverbal affiliation cues (SNAC), and behavioral indicators of positivity resonance (BIPR). To evaluate construct validity, we conducted a confirmatory factor analysis to test a latent factor of positivity resonance encompassing coexperienced positive affect, coexpressed positive affect, physiological linkage of interbeat heart intervals, SNAC, and BIPR. The model showed excellent fit. To evaluate associations with health and longevity, we used dyadic latent growth curve modeling and Cox proportional hazards modeling, respectively, and found that greater latent positivity resonance predicted less steep declines in health and increased longevity. Associations were robust when accounting for initial health symptoms, sociodemographic characteristics, health-related behaviors, and individually experienced positive affect. We repeated health and longevity analyses, replacing latent positivity resonance with BIPR, and found consistent results. Findings validate positivity resonance as a multimodal construct, support the utility of the BIPR measure, and provide initial evidence for the characterization of positivity resonance as a positive health behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ObjectiveTo summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market.DesignSummary of the one-day workshop held virtually on June 22nd, 2021.ResultsSpeakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.ConclusionsDemonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Disability support (DS) offices provide accommodations for and serve qualified students with disabilities. The overall number of students with disabilities in higher education is increasing, creating a need for high-impact, effective support. Proactive advising is a method of support that provides college students tools for success before crises occur. Most proactive advising for students with disabilities focuses on a narrow population (e.g., students with ADHD or learning disabilities). However, DS offices serve a diverse array of diagnoses. 2-4-8 is a proactive advising model in which all students with documented disabilities meet individually with a DS staff member at least three times in the fall semester to ensure that accommodations, supports, and skills necessary for success in higher education are in place. This study was a preliminary investigation of perceived academic skills before and after participation in 2-4-8. Initial findings indicate that self-reported organization, time management, professor communication, and studying were significantly improved through 2-4-8, and that perceptions of test taking, self-advocacy, and meeting deadlines were slightly, though non-significantly, improved. This study provides promising evidence that 2-4-8 could be a useful resource to provide proactive, quality support that meets the diverse needs of college students with disabilities.

Purpose: The present study analyzes differences in self-perceived employability (SPE) among Spanish university and vocational education and training (VET) students. It also aims to determine whether factors such as gender, work experience and perceptions of the precariousness of the job market have a differential effect on SPE in accordance with the training pathway chosen by emerging adults. Design/methodology/approach: A total of 1,715 university students (64.7% women) and 488 VET students (37.1% women) aged between 18 and 29 years completed a self-administered questionnaire that included measures of perceived employability and precarious employment. Findings: The results indicate higher SPE among VET students than among their university counterparts. Female university students scored lower also than their male colleagues, an effect that was not observed among VET students. Prior work experience improved internal SPE among students on both training pathways. However, among university students, work experience and precarious employment reduced external SPE, an affect that was not observed among VET students. Practical implications: The analysis of differences in SPE between university and VET students highlights the importance of an educational curriculum that includes practical competences for enhancing employability. The results also reflect the negative consequences of precarious employment on feelings of employability during this life stage, particularly among those studying at university. Originality/value: This is one of the first studies to analyze the perceived employability of emerging adults on two different training pathways in Spain.

Young adults with autism spectrum disorder (ASD) experience a variety of unique challenges that may be compounded for individuals pursuing postsecondary education. Particular difficulties identified for college students with ASD include variability in social skills, social isolation, and reduced access to appropriate support and services. Research on effective interventions supporting college students with ASD is considerably lacking. This pilot study sought to address this area of need by modifying the Program for the Education and Enrichment of Relational Skills (PEERS) for Young Adults, a social skills training program for young adults with autism, for use on a college campus. Following the intervention, participants showed improvements in areas of social functioning that are particularly important for college students with ASD, including overall social functioning, social awareness, social motivation, social cognition, and knowledge of social skills. This study is an important step toward the development of effective interventions that address social competence specifically for young adults with autism in postsecondary educational environments.

There is an urgent need for transformational change in global and UK agriculture. Current practices undermine the long-term future of farming and impoverish ecosystems in the UK and elsewhere. However, change is not happening at the scale and pace which is needed. Work by David Abson, drawing on ideas by Donella Meadows, explored this failure of progress and proposed a research agenda focused on transformational leverage points which influence sustainability. These points are centred on three realms of leverage: reconnecting people to nature, restructuring institutions and rethinking how knowledge is created and used in pursuit of sustainability. In this paper, these ideas are explored through a combined researcher/stakeholder workshop focused on transformational change in UK livestock systems. Workshop participants were asked to discuss and identify potential levers of change under the three realms identified by Abson. The multiplicity of levers identified and the interactions across realms emphasise the need for new kinds of knowledge creation which are highly transdisciplinary, as well as emphasising the complexity of levers which are likely to play a role in the transformation of livestock food systems in the UK and elsewhere.

ABSTRACT Superficial infections of the skin, hair, and nails by fungal dermatophytes are the most prevalent of human mycoses, and many infections are refractory to treatment. As current treatment options are limited, recent research has explored drug synergy with azoles for dermatophytoses. Bisphosphonates, which are approved to treat osteoporosis, can synergistically enhance the activity of azoles in diverse yeast pathogens but their activity has not been explored in dermatophytes or other molds. Market bisphosphonates risedronate, alendronate, and zoledronate (ZOL) were evaluated for antifungal efficacy and synergy with three azole antifungals: fluconazole (FLC), itraconazole (ITR), and ketoconazole (KET). ZOL was the most active bisphosphonate tested, displaying moderate activity against nine dermatophyte species (MIC range 64–256 µg/mL), and was synergistic with KET in eight of these species. ZOL was also able to synergistically improve the anti-biofilm activity of KET and combining KET and ZOL prevented the development of antifungal resistance. Rescue assays in Trichophyton rubrum revealed that the inhibitory effects of ZOL alone and in combination with KET were due to the inhibition of squalene synthesis. Fluorescence microscopy using membrane- and ROS-sensitive probes demonstrated that ZOL and KET:ZOL compromised membrane structure and induced oxidative stress. Antifungal activity and synergy between bisphosphonates and azoles were also observed in other clinically relevant molds, including species of Aspergillus and Mucor. These findings indicate that repurposing bisphosphonates as antifungals is a promising strategy for revitalising certain azoles as topical antifungals, and that this combination could be fast-tracked for investigation in clinical trials.IMPORTANCEFungal infections of the skin, hair, and nails, generally grouped together as “tineas” are the most prevalent infectious diseases globally. These infections, caused by fungal species known as dermatophytes, are generally superficial, but can in some cases become aggressive. They are also notoriously difficult to resolve, with few effective treatments and rising levels of drug resistance. Here, we report a potential new treatment that combines azole antifungals with bisphosphonates. Bisphosphonates are approved for the treatment of low bone density diseases, and in fungi they inhibit the biosynthesis of the cell membrane, which is also the target of azoles. Combinations were synergistic across the dermatophyte species and prevented the development of resistance. We extended the study to molds that cause invasive disease, finding synergy in some problematic species. We suggest bisphosphonates could be repurposed as synergents for tinea treatment, and that this combination could be fast-tracked for use in clinical therapy.

Summary: Background: Obesity is highly stigmatized, with negative obesity-related stereotypes widespread across society. Internalized weight stigma (IWS) is linked to negative outcomes including poor mental health and disordered eating. Previous evidence examining population groups at higher risk of experiencing IWS comes from small, nonrepresentative samples. Here, we re-assess previously reported associations of IWS with demographic, socioeconomic, and wider social factors in a large general population birth cohort study for the first time. Methods: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored differences in IWS at age 31 years by sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences, using confounder-adjusted multivariable regression. Findings: In models adjusted for potential confounders and BMI in childhood, adolescence, and adulthood (N = 4060), IWS was higher for females (standardized beta: 0.56, 95% CI: 0.50, 0.61), sexual minorities (0.17 S.D. higher, 95% CI: 0.09, 0.24), and less socioeconomically advantaged individuals (e.g., 0.16 S.D. higher (95% CI: 0.08, 0.24) for participants whose mothers had minimum or no qualifications, compared to a university degree). The social environment during adolescence and young adulthood was important: IWS was higher for people who at age 13 years felt pressure to lose weight from family (by 0.13 S.D., 95% CI: 0.03, 0.23), and the media (by 0.17, 95% CI: 0.10, 0.25), or had experienced bullying (e.g., 0.25 S.D., 95% CI: 0.17, 0.33 for bullying at age 23 years). Interpretation: Internalized weight stigma differs substantially between demographic groups. Risk is elevated for females, sexual minorities, and socioeconomically disadvantaged adults, and this is not explained by differences in BMI. Pressure to lose weight from family and the media in adolescence may have long-lasting effects on IWS. Funding: The ESRC, MRC, NIHR, and Wellcome Trust.

There is little robust evidence of how sustainable park interventions impact on physical activity and other behaviours important for wellbeing. This controlled natural experimental study aimed to examine the effects of co-designing a sustainable park intervention, in a deprived UK urban area, on walking and other wellbeing behaviours.Behaviour observations were conducted at two intervention sites and two matched comparison sites (n = 4,783). Walking observations (primary outcome), wellbeing behaviours (vigorous, sedentary, social and take notice activities) and demographic characteristics were assessed at pre-intervention, and post-intervention (3 and 15 months). Outcomes were compared between intervention and comparison groups, controlling for pre-intervention using multilevel negative binomial regression models. Additional behaviour observations were conducted in two unchanged nearby sites to assess changes in general local activity. Intercept surveys (n = 623) assessed change in self-reported outdoor space usage at intervention and control areas.Post-intervention, walking increased 203 % at 3 months (IRR 2·03, 95 % CI 1·01-4·09) and 351 % at 15 months (IRR 3·51, 95 % CI 2·07-5·93), for intervention sites relative to comparison sites. Large increases for other wellbeing behaviours were also observed. The proportion of non-white persons increased substantially post-intervention, compared to comparison sites. Nearby unchanged sites showed little evidence of general increased activity. Self-reported outdoor usage increased more in the intervention sites (p=

Two blue whiting protein hydrolysates (BWPHs) with potent in situ and in vitro antidiabetic and antioxidant activities were fractionated. Potent fractions were analysed using LC-MS/MS. Peptides VPVE and IPQD exhibited potent in situ DPP-IV inhibitory activity (Caco-2 cells) with IC50 values of 88.79 ± 5.40 and 91.12 ± 19.73 µM, respectively. Significant decreases in ROS production observed (HepG2 cells) with MPKKE, GPAG and MPAH. MPAH and LPDDL significantly (p

Climate change is predicted to negatively impact calcification and change the structural integrity of biogenic carbonates, influencing their protective function. We assess the impacts of warming on the morphology and crystallography of Amphistegina lobifera, an abundant benthic foraminifera species in shallow environments. Specimens from a thermally disturbed field area, mimicking future warming, are about 50% smaller compared with a control location. Differences in the position of the ν1 Raman mode of shells between the sites, which serves as a proxy for Mg content and calcification temperature, indicate that calcification is negatively impacted when temperatures are below the thermal range facilitating calcification. To test the impact of thermal stress on the Young's modulus of calcite which contributes to structural integrity, we quantify elasticity changes in large benthic foraminifera by applying atomic force microscopy to a different genus, Operculina ammonoides, cultured under optimal and high temperatures. Building on these observations of size and the sensitivity analysis for temperature-induced change in elasticity, we used finite element analysis to show that structural integrity is increased with reduced size and is largely insensitive to calcite elasticity. Our results indicate that warming-induced dwarfism creates shells that are more resistant to fracture because they are smaller.

This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions.

The aim of this study was to compare the dosimetry of carotid arteries (CAs) using three radiation therapy (RT) techniques, three-dimensional conformal RT (3D-CRT), helical tomotherapy-intensity-modulated RT (HT-IMRT), and volumetric modulated arc therapy (VMAT), in patients with early-stage glottic cancer.

Anatomically preserved lycophytes of the Lycopodiales and Selaginellales have been discovered among a diverse assemblage of plants and fungi in carbonate marine concretions at the Apple Bay locality along the shore of Holbert Inlet near the northern end of Vancouver Island, British Columbia, Canada. Lycopodialean stems are plectostelic and actinostelic, branch dichotomously, and are similar to both Lycopodicaulis oellgaardii and Lycoxylon spp. The Selaginella specimens represent the first anatomically preserved Selaginellales with excellent internal cellular preservation in the fossil record, and are described as Selaginella quatsinoense Rothwell et Stockey sp. nov. Stems have three and five exarch, monarch stelar segments, each of which is surrounded by an aerenchymatous endodermis with trabeculae. The leaf base is indented on the adaxial surface, suggesting the position of a ligule. These fossils document that species with diagnostic internal anatomy of modern Lycopodiales and Selaginellales evolved no later than the Valanginian of the early Cretaceous.

Re-irradiation as a therapeutic option for locoregional recurrence in patients with recurrent, persistent tumour or second primary malignant neoplasm has great advantages for locally advanced unresectable tumours.

Intranasal oxytocin (IN OXT) administration has been proposed as a pharmacological treatment for a range of biomedical conditions including neurodevelopmental disorders. However, studies evaluating the potential long-lasting effects of chronic IN OXT during development are still scarce. Here we conducted a follow-up study of a cohort of adult titi monkeys that received intranasal oxytocin 0.8 IU/kg (n = 15) or saline (n = 14) daily for six months during their juvenile period (12 to 18 months of age), with the goal of evaluating the potential long-lasting behavioral and neural effects one year post-treatment. Subjects were paired with an opposite-sex mate at 30 months of age (one year post-treatment). We examined pair affiliative behavior in the home cage during the first four months and tested for behavioral components of pair bonding at one week and four months post-pairing. We assessed long-term changes in brain glucose uptake using 18FDG positron emission tomography (PET) scans. Our results showed that OXT-treated animals were more affiliative across a number of measures, including tail twining, compared to SAL treated subjects (tail twining is considered the "highest" type of affiliation in titi monkeys). Neuroimaging showed no treatment differences in glucose uptake between SAL and OXT-treated animals; however, females showed higher glucose uptake in whole brain at 23 months, and in both the whole brain and the social salience network at 33 months of age compared to males. Our results suggest that chronic IN OXT administration during development can have long-term effects on adult social behavior.

Summary: Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p

Background and aimRapid outpatient evaluation and treatment of TIA in structured clinics have been shown to reduce stroke recurrence. It is unclear whether short-term downtrends in TIA incidence and admissions have had enduring impact on TIA clinic activity. This study aims to measure the impact of the pandemic on hospitals with rapid TIA clinics.MethodsRelevant services were identified by literature search and contacted. Three years of monthly data were requested – a baseline pre-COVID period (April 2018 to March 2020) and an intra-COVID period (April 2020 to March 2021). TIA presentations, ischemic stroke presentations, and reperfusion trends inclusive of IV thrombolysis (IVT) and endovascular thrombectomy (EVT) were recorded. Pandemic impact was measured with interrupted time series analysis, a segmented regression approach to test an effect of an intervention on a time-dependent outcome using a defined impact model.ResultsSix centers provided data for a total of 6,231 TIA and 13,191 ischemic stroke presentations from Australia (52.1%), Canada (35.0%), Italy (7.6%), and England (5.4%). TIA clinic volumes remained constant during the pandemic (2.9, 95% CI –1.8 to 7.6, p = 0.24), as did ischemic stroke (2.9, 95% CI –7.8 to 1.9, p = 0.25), IVT (−14.3, 95% CI −36.7, 6.1, p

Purpose: The goal of this article is to explore what online education and decision support tools are freely available to patients about prenatal screening. Methods: We (1) conducted an environmental scan using Google Trends to identify and evaluate prenatal screening search terms, (2) created a list of websites and YouTube videos that would be easily accessed by a searcher, and (3) characterized the information within those websites and videos, including an examination of their qualities as a decision support tool and a readability analysis. Results: Fifty websites, containing 62 unique educational resources, and 39 YouTube videos were analyzed. The websites were primarily educational, although the education was provided by a range of sources, including non-profit and for-profit organizations, universities, and governments (ie, public health departments). Readability scores of Patient Education Materials Assessment Tool for Printable Materials for the sites ranged from 50% to 92%, with a median score of 74%. Two of the websites we evaluated met all of the limited decision support standards we applied; 4 of the websites included patient stories or experiences, and 8 included some element of values clarification. Videos were more likely to include values clarification. Conclusion: The information available to patients online is variable. Although most is balanced and informative, much is difficult to read and missing key decision-making factors. Health care providers should work with patients to ensure they have basic comprehension of the prenatal genetic screening materials, possible result outcomes, and expected steps following a positive screening result.

Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patient(s): A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Intervention(s): In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measure(s): The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Result(s): In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusion(s): Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Abstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Results Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. Conclusion These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.