Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol.

INTRODUCTION: Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map

Early characterization of the severity and transmissibility of pandemic influenza using clinical episode data from multiple populations

The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics

Manifesto for a European research network into Problematic Usage of the Internet

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.Peer reviewe

Empirical Evaluation of the Difficulty of Finding a Good Value of k for the Nearest Neighbor

As an analysis of the classification accuracy bound for the Nearest Neighbor technique, in this work we have studied if it is possible to find a good value of the parmeter k for each example according to their attribute values. Or at least, if there is a pattern for the parameter k in the original search space. We have carried out different approaches based onthe Nearest Neighbor technique and calculated the prediction accuracy for a group of databases from the UCI repository. Based on the experimental results of our study, we can state that, in general, it is not possible to know a priori a specific value of k to correctly classify an unseen example

Screen Use and Mental Health Symptoms in Canadian Children and Youth during the COVID-19 Pandemic

Importance: Longitudinal research on specific forms of electronic screen use and mental health symptoms in children and youth during COVID-19 is minimal. Understanding the association may help develop policies and interventions targeting specific screen activities to promote healthful screen use and mental health in children and youth. Objective: To determine whether specific forms of screen use (television [TV] or digital media, video games, electronic learning, and video-chatting time) were associated with symptoms of depression, anxiety, conduct problems, irritability, hyperactivity, and inattention in children and youth during COVID-19. Design, Setting, and Participants: A longitudinal cohort study with repeated measures of exposures and outcomes was conducted in children and youth aged 2 to 18 years in Ontario, Canada, between May 2020 and April 2021 across 4 cohorts of children or youth: 2 community cohorts and 2 clinically referred cohorts. Parents were asked to complete repeated questionnaires about their children\u27s health behaviors and mental health symptoms during COVID-19. Main Outcomes and Measures: The exposure variables were children\u27s daily TV or digital media time, video game time, electronic-learning time, and video-chatting time. The mental health outcomes were parent-reported symptoms of child depression, anxiety, conduct problems and irritability, and hyperactivity/inattention using validated standardized tools. Results: This study included 2026 children with 6648 observations. In younger children (mean [SD] age, 5.9 [2.5] years; 275 male participants [51.7%]), higher TV or digital media time was associated with higher levels of conduct problems (age 2-4 years: β, 0.22 [95% CI, 0.10-0.35]; P \u3c.001; age ≥4 years: β, 0.07 [95% CI, 0.02-0.11]; P =.007) and hyperactivity/inattention (β, 0.07 [95% CI, 0.006-0.14]; P =.04). In older children and youth (mean [SD] age, 11.3 [3.3] years; 844 male participants [56.5%]), higher levels of TV or digital media time were associated with higher levels of depression, anxiety, and inattention; higher levels of video game time were associated with higher levels of depression, irritability, inattention, and hyperactivity. Higher levels of electronic learning time were associated with higher levels of depression and anxiety. Conclusions and Relevance: In this cohort study, higher levels of screen use were associated poor mental health of children and youth during the COVID-19 pandemic. These findings suggest that policy intervention as well as evidence-informed social supports are needed to promote healthful screen use and mental health in children and youth during the pandemic and beyond

Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation

Telomere length homeostasis is essential for the long-term survival of stem cells, and its set point determines the proliferative capacity of differentiated cell lineages by restricting the reservoir of telomeric repeats. Knockdown and overexpression studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres through a region termed the TEL patch. However, these studies do not resolve whether the TPP1 TEL patch is the only mechanism for telomerase recruitment and whether telomerase regulation studied in tumor cells is representative of nontransformed cells such as stem cells. Using genome engineering of human embryonic stem cells, which have physiological telomere length homeostasis, we establish that the TPP1 TEL patch is genetically essential for telomere elongation and thus long-term cell viability. Furthermore, genetic bypass, protein fusion, and intragenic complementation assays define two distinct additional mechanisms of TPP1 involvement in telomerase action at telomeres. We demonstrate that TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis. Keywords: embryonic stem cells; human genome engineering; shelterin; telomerase telomere maintenanceNational Institutes of Health (U.S.) (Grant R37-CA084198)National Institutes of Health (U.S.) (Grant RO1-CA087869)National Institutes of Health (U.S.) (Grant RO1-HD045022

Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation

Telomere length homeostasis is essential for the long-term survival of stem cells, and its set point determines the proliferative capacity of differentiated cell lineages by restricting the reservoir of telomeric repeats. Knockdown and overexpression studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres through a region termed the TEL patch. However, these studies do not resolve whether the TPP1 TEL patch is the only mechanism for telomerase recruitment and whether telomerase regulation studied in tumor cells is representative of nontransformed cells such as stem cells. Using genome engineering of human embryonic stem cells, which have physiological telomere length homeostasis, we establish that the TPP1 TEL patch is genetically essential for telomere elongation and thus long-term cell viability. Furthermore, genetic bypass, protein fusion, and intragenic complementation assays define two distinct additional mechanisms of TPP1 involvement in telomerase action at telomeres. We demonstrate that TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis

Progression-free survival as a surrogate endpoint for overall survival in patients with relapsed or refractory multiple myeloma

Objectives: The goal of the research was to assess the quantitative relationship between median progression-free survival (PFS) and median overall survival (OS) specifically among patients with relapsed/refractory multiple myeloma (RRMM) based on published randomized controlled trials (RCTs). Methods: Two bibliographic databases (PubMed and Embase, 1970–2017) were systematically searched for RCTs in RRMM that reported OS and PFS, followed by an updated search of studies published between 2010 and 2022 in 3 databases (Embase, MEDLINE, and EBM Reviews, 2010–2022). The association between median PFS and median OS was assessed using the nonparametric Spearman rank and parametric Pearson correlation coefficients. Subsequently, the quantitative relationship between PFS and OS was assessed using weighted least-squares regression adjusted for covariates including age, sex, and publication year. Study arms were weighted by the number of patients in each arm. Results: A total of 31 RCTs (56 treatment arms, 10,450 patients with RRMM) were included in the analysis. The average median PFS and median OS were 7.1 months (SD 5.5) and 28.1 months (SD 11.8), respectively. The Spearman and Pearson correlation coefficients between median PFS and median OS were 0.80 (P &lt; 0.0001) and 0.79 (P &lt; 0.0001), respectively. In individual treatment arms of RRMM trials, each 1-month increase in median PFS was associated with a 1.72-month (95% CI 1.26–2.17) increase in median OS. Conclusion: Analysis of the relationship between PFS and OS incorporating more recent studies in RRMM further substantiates the use of PFS to predict OS in RRMM.</p

Relative age effect across the talent identification process of youth female soccer players in the United States: influence of birth year, position, biological maturation, and skill level

The aims of the study were to examine the relative age effect (RAE) in youth female soccer players in the United States (US) and the influence of birth year, playing position, estimated maturation and skill ratings. The sample consisted of 3,364 youth female soccer players who were active in the 2021–2022 US soccer season across three main stages of the talent identification (TID) process for Youth National Team (YNT) players (i.e., Club, TID Center, and YNT). A prevalent RAE for players born in Q1 was present in the full sample. A significant prevalence for Q1 players were identified for both Club and TID Center, but not YNT. A significant RAE prevalence for Q1 players was identified for most of the age groups from U13–U18 at Club (except U18) and TID Center (except U17). Significant RAEs prevalence for players born in Q1 were found in Goalkeepers, Center Backs, Midfielders, and Center Forwards at Club and TID Center (except Wide Forwards). The data identified a consistent RAE prevalence for Q1 players in early and on-time-maturers across all levels. An even birthdate spread was evident in YNT with a prevalence for Q4 players and a higher percentage of late maturers than elsewhere in the TID process. Results reinforce evidence indicating RAEs still exist in soccer, yet show for the first time within a youth female soccer TID process, the influence of contextual factors on the prevalence of RAE. This information can be used to advance TID and development across the US soccer landscape