Response rates and selection problems, with emphasis on mental health variables and DNA sampling, in large population-based, cross-sectional and longitudinal studies of adolescents in Norway

Background Selection bias is a threat to the internal validity of epidemiological studies. In light of a growing number of studies which aim to provide DNA, as well as a considerable number of invitees who declined to participate, we discuss response rates, predictors of lost to follow-up and failure to provide DNA, and the presence of possible selection bias, based on five samples of adolescents. Methods We included nearly 7,000 adolescents from two longitudinal studies of 18/19 year olds with two corresponding cross-sectional baseline studies at age 15/16 (10th graders), and one cross-sectional study of 13th graders (18/19 years old). DNA was sampled from the cheek mucosa of 18/19 year olds. Predictors of lost to follow-up and failure to provide DNA were studied by Poisson regression. Selection bias in the follow-up at age 18/19 was estimated through investigation of prevalence ratios (PRs) between selected exposures (physical activity, smoking) and outcome variables (general health, mental distress, externalizing problems) measured at baseline. Results Out of 5,750 who participated at age 15/16, we lost 42% at follow-up at age 18/19. The percentage of participants who gave their consent to DNA provision was as high as the percentage that consented to a linkage of data with other health registers and surveys, approximately 90%. Significant predictors of lost to follow-up and failure to provide DNA samples in the present genetic epidemiological study were: male gender; non-western ethnicity; postal survey compared with school-based; low educational plans; low education and income of father; low perceived family economy; unmarried parents; poor self-reported health; externalized symptoms and smoking, with some differences in subgroups of ethnicity and gender. The association measures (PRs) were quite similar among participants and all invitees, with some minor discrepancies in subgroups of non-western boys and girls. Conclusions Lost to follow-up had marginal impact on the estimated prevalence ratios. It is not likely that the invitation to provide DNA influenced the response rates of 18/19 year olds. Non-western ethnicity, male gender and characteristics related to a low social class and general and mental health problems measured at baseline are associated with lost to follow-up and failure to provide DNA

Identification of Eps15 as Antigen Recognized by the Monoclonal Antibodies aa2 and ab52 of the Wuerzburg Hybridoma Library against Drosophila Brain

The Wuerzburg Hybridoma Library against the Drosophila brain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15) as the antigen for these two antibodies

In praise of arrays

Microarray technologies have both fascinated and frustrated the transplant community since their introduction roughly a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to immunogenic injury and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analyses, and difficulties associated with actually recognizing signature gene-expression patterns and discerning mechanisms. To aid the understanding of this powerful tool, its versatility, and how it is dramatically changing the molecular approach to biomedical and clinical research, this teaching review describes the technology and its applications, as well as the limitations and evolution of microarrays, in the field of organ transplantation. Finally, it calls upon the attention of the transplant community to integrate into multidisciplinary teams, to take advantage of this technology and its expanding applications in unraveling the complex injury circuits that currently limit transplant survival

The impact of gastrointestinal symptoms and dermatological injuries on nutritional intake and hydration status during ultramarathon events

BACKGROUND: Debilitating gastrointestinal symptoms (GIS) and dermatological injuries (DI) are common during and after endurance events and have been linked to performance decrements, event withdrawal, and issues requiring medical attention. The study aimed to determine whether GIS and DI affect food and fluid intake, and nutritional and hydration status, of ultramarathon runners during multi-stage (MSUM) and 24-h continuous (24 h) ultramarathons. METHODS: Ad libitum food and fluid intakes of ultramarathon runners (MSUM n = 54; 24 h n = 22) were recorded throughout both events and analysed by dietary analysis software. Body mass and urinary ketones were determined, and blood samples were taken, before and immediately after running. A medical log was used to monitor symptoms and injuries throughout both events. RESULTS: GIS were reported by 85 and 73 % of ultramarathon runners throughout MSUM and 24 h, respectively. GIS during MSUM were associated with reduced total daily, during, and post-stage energy and macronutrient intakes (p < 0.05), whereas GIS during 24 h did not alter nutritional variables. Throughout the MSUM 89 % of ultramarathon runners reported DI. DI during MSUM were associated with reduced carbohydrate (p < 0.05) intake during running and protein intake post-stage (p < 0.05). DI during 24 h were low; thus, comparative analyses were not possible. Daily, during running, and post-stage energy, macronutrient and water intake variables were observed to be lower with severity of GIS and DI (p < 0.05) throughout the MSUM only. CONCLUSIONS: GIS during the MSUM, but not the 24 h, compromised nutritional intake. DI presence and severity also compromised nutrient intake during running and recovery in the MSUM

Multiscale multifactorial approaches for engineering tendon substitutes

The physiology of tendons and the continuous strains experienced daily make tendons very prone to injury. Excessive and prolonged loading forces and aging also contribute to the onset and progression of tendon injuries, and conventional treatments have limited efficacy in restoring tendon biomechanics. Tissue engineering and regenerative medicine (TERM) approaches hold the promise to provide therapeutic solutions for injured or damaged tendons despite the challenging cues of tendon niche and the lack of tendon-specific factors to guide cellular responses and tackle regeneration. The roots of engineering tendon substitutes lay in multifactorial approaches from adequate stem cells sources and environmental stimuli to the construction of multiscale 3D scaffolding systems. To achieve such advanced tendon substitutes, incremental strategies have been pursued to more closely recreate the native tendon requirements providing structural as well as physical and chemical cues combined with biochemical and mechanical stimuli to instruct cell behavior in 3D architectures, pursuing mechanically competent constructs with adequate maturation before implantation.Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marinederived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Authors acknowledge the H2020 Achilles Twinning Project No. 810850, and also the European Research Council CoG MagTendon No. 772817, and the FCT Project MagTT PTDC/CTM-CTM/ 29930/2017 (POCI-01-0145-FEDER-29930

Iterated elimination procedures

We study the existence and uniqueness (i.e.,order independence) of any arbitrary form of iterated elimination procedures in an abstract environment. By allowing for a transfinite elimination, we show a general existence of the iterated elimination procedure. Inspired by the seminal work of Gilboa, Kalai and Zemel (1990), we identify a fairly weak suffcient condition of Monotonicity* for the order independence of iterated elimination procedure. Monotonicity* requires a monotonicity property along any elimination path. Our approach is applicable to different forms of iterated elimination procedures used in (in)finite games, for example, iterated elimination of strictly dominated strategies, iterated elimination of weakly dominated strategies, rationalizability, and soon. We introduce a notion of CD* games, which incorporates Jackson's (1992) idea of "boundedness", and show the iterated elimination procedure is order independent in the class of CD* games. In finite games, we also formulate and show an "outcome" order-independence result suitable for Marx and Swinkels's (1997) notion of nice weak dominance

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research