Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2λ that ...binds human TSLP and prevents receptor interaction.
In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge.
AMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events.
Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.).
There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been ...comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed.
The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored.
Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality".
Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.
The persistent use of psychostimulant drugs, despite the detrimental outcomes associated with continued drug use, may be because of disruptions in reinforcement-learning processes that enable ...behavior to remain flexible and goal directed in dynamic environments. To identify the reinforcement-learning processes that are affected by chronic exposure to the psychostimulant methamphetamine (MA), the current study sought to use computational and biochemical analyses to characterize decision-making processes, assessed by probabilistic reversal learning, in rats before and after they were exposed to an escalating dose regimen of MA (or saline control). The ability of rats to use flexible and adaptive decision-making strategies following changes in stimulus-reward contingencies was significantly impaired following exposure to MA. Computational analyses of parameters that track choice and outcome behavior indicated that exposure to MA significantly impaired the ability of rats to use negative outcomes effectively. These MA-induced changes in decision making were similar to those observed in rats following administration of a dopamine D2/3 receptor antagonist. These data use computational models to provide insight into drug-induced maladaptive decision making that may ultimately identify novel targets for the treatment of psychostimulant addiction. We suggest that the disruption in utilization of negative outcomes to adaptively guide dynamic decision making is a new behavioral mechanism by which MA rigidly biases choice behavior.
Widespread diffusion of mobile phone and Web 2.0 technologies make them potentially useful tools for promoting health and tackling public health issues, such as the increasing prevalence of ...overweight and obesity. Research in this domain is growing rapidly but, to date, no review has comprehensively and systematically documented how mobile and Web 2.0 technologies are being deployed and evaluated in relation to weight management.
To provide an up-to-date, comprehensive map of the literature discussing the use of mobile phone and Web 2.0 apps for influencing behaviors related to weight management (ie, diet, physical activity PA, weight control, etc).
A systematic scoping review of the literature was conducted based on a published protocol (registered at
CRD42014010323). Using a comprehensive search strategy, we searched 16 multidisciplinary electronic databases for original research documents published in English between 2004 and 2014. We used duplicate study selection and data extraction. Using an inductively developed charting tool, selected articles were thematically categorized.
We identified 457 articles, mostly published between 2013 and 2014 in 157 different journals and 89 conference proceedings. Articles were categorized around two overarching themes, which described the use of technologies for either (1) promoting behavior change (309/457, 67.6%) or (2) measuring behavior (103/457, 22.5%). The remaining articles were overviews of apps and social media content (33/457, 7.2%) or covered a combination of these three themes (12/457, 2.6%). Within the two main overarching themes, we categorized articles as representing three phases of research development: (1) design and development, (2) feasibility studies, and (3) evaluations. Overall, articles mostly reported on evaluations of technologies for behavior change (211/457, 46.2%).
There is an extensive body of research on mobile phone and Web 2.0 technologies for weight management. Research has reported on (1) the development, feasibility, and efficacy of persuasive mobile technologies used in interventions for behavior change (PA and diet) and (2) the design, feasibility, and accuracy of mobile phone apps for behavioral assessment. Further research has focused exclusively on analyses of the content and quality of available apps. Limited evidence exists on the use of social media for behavior change, but a segment of studies deal with content analyses of social media. Future research should analyze mobile phone and Web 2.0 technologies together by combining the evaluation of content and design aspects with usability, feasibility, and efficacy/effectiveness for behavior change, or accuracy/validity for behavior assessment, in order to understand which technological components and features are likely to result in effective interventions.
Abstract
We present the first spatially resolved maps of gas-phase metallicity for two dust-obscured star-forming galaxies at
z
∼ 4, from the JWST TEMPLATES Early Release Science program, derived ...from NIRSpec integral field unit spectroscopy of the H
α
and N
ii
emission lines. Empirical optical line calibrations are used to determine that the sources are globally enriched to near-solar levels. While one source shows elevated N
ii
/H
α
ratios and broad H
α
emission consistent with the presence of an active galactic nucleus in a ≳1 kpc region, we argue that both systems have already undergone significant metal enrichment as a result of their extremely high star formation rates. Utilizing Atacama Large Millimeter/submillimeter Array rest-frame 380
μ
m continuum and C
i
(
3
P
2
–
3
P
1
) line maps we compare the spatial variation of the metallicity and gas-to-dust ratio in the two galaxies, finding the two properties to be anticorrelated on highly resolved spatial scales, consistent with various literature studies of
z
∼ 0 galaxies. The data are indicative of the enormous potential of JWST to probe the enrichment of the interstellar medium on ∼kpc scales in extremely dust-obscured systems at
z
∼ 4 and beyond.
Évaluation complète d’une étude de cohorte canadienne portant sur la démence et la neuro-dégénérescence. Contexte : L’évaluation globale de la neuro-dégénérescence et de la démence (COMPASS-ND), ...étude de cohorte du Consortium canadien en neuro-dégénérescence associée au vieillissement (CCNV), représente une initiative nationale visant à promouvoir la recherche portant sur la démence et à soutenir les programmes de recherche des équipes du CCNV. Totalisant 2310 sujets recrutés partout au pays, cette cohorte longitudinale regroupe des individus fortement « phénotypés » qui présentent diverses formes de démence et de pertes de mémoire légères. En plus de sujets âgés dont les fonctions cognitives sont intactes, ces 2310 sujets ont permis de valider les hypothèses formulées par les équipes du CCNV. Méthodes : Nous avons utilisé de nombreux documents pour décrire cette étude : le protocole de la COMPASS-ND ; la demande initiale de subvention ; le cinquième rapport d’étape semi-annuel du CCNV soumis aux Instituts de recherche en santé du Canada (IRSC) en décembre 2017 ; ainsi que d’autres documents produits à la suite de modifications consécutives à la mise en œuvre de ce projet. Résultats : L’étude de cohorte COMPASS-ND du CCNV inclut des participants de partout au Canada dont les divers états cognitifs sont associés à des maladies neurodégénératives ou au risque d’en souffrir. Ils feront l’objet d’un large éventail d’examens expérimentaux, cliniques, génétiques et d’imagerie afin d’aborder de manière spécifique les causes, le diagnostic, le traitement et la prévention de ces états cognitifs chez les personnes âgées. Les données obtenues à la suite d’évaluations cliniques et cognitives, ainsi que celles issues d’échantillons biologiques, d’imagerie cérébrale, de tests génétiques et de dons de cerveaux, seront utilisées pour tester les hypothèses générées par les équipes de recherche du CCNV et d’autres chercheurs canadiens. Cette étude constitue donc à ce jour l’étude canadienne la plus complète et la plus ambitieuse au sujet de la démence. La présentation des données initiales ayant eu lieu en 2018, la cohorte devrait atteindre sa taille maximale d’ici à 2020.Conclusion : La disponibilité des données de l’étude COMPASS-ND stimulera considérablement la recherche sur la démence au Canada au cours des prochaines années.
IntroductionAttention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with an average worldwide prevalence of 5%. Up to 40% of young ...people continue to experience symptoms into adulthood. Young people with ADHD experience poorer outcomes than their peers across multiple domains, with treatment shown to reduce these risks. Primary care practitioners play an important role in healthcare provision for this group in the UK. However, many feel unsure about how best to provide support, reporting prescribing concerns and need for more evidence-based guidance. A lack of national data on primary care provision hinders efforts to improve access to care and optimise outcomes. This mixed-methods study aims to provide evidence that may be used to improve primary care services for young people aged 16–25 years with ADHD.Methods and analysisThere are three interlinked work packages: (a) a mapping study including a survey of stakeholders (healthcare professionals, people with ADHD and commissioners) will map ADHD prescribing practice, shared-care arrangements, available support and practitioner roles by geographic locations across England for different respondent groups; (b) a qualitative study involving semi-structured interviews with stakeholders (10–15 healthcare professionals and 10–15 people with ADHD) will explore experiences of ‘what works’ and ‘what is needed’ in terms of service provision and synthesise findings; (c) workshops will integrate findings from (a) and (b) and work with stakeholders to use this evidence to codevelop key messages and guidance to improve care.Ethics and disseminationThe protocol has been approved by Yorkshire and the Humber—Bradford Leeds Research Ethics Committee. Recruitment commenced in September 2022. Findings will be disseminated via research articles in peer-reviewed journals, conference presentations, public involvement events, patient groups and media releases. A summary of study findings will be shared with participants at the end of the study.Trial registration numberNCT05518435.
Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder. UK guidance states that primary care has a vital role in effective ADHD management, including ...referral, medication prescribing and monitoring, and providing broader mental health and wellbeing support. However, many GPs feel unsupported to provide health care for young people with ADHD. Inadequate health care is associated with rising costs for patients and society.
To investigate the experiences of young people with ADHD accessing primary care in England, from the perspectives of people with lived experience of ADHD and healthcare professionals (HCPs).
A qualitative study. Interviews were conducted with HCPs (GPs, practice managers, and a wellbeing worker) and people with lived experience of ADHD (young people aged 16-25 years and their supporters) located in integrated care systems across England.
Semi-structured interviews were conducted with participants at five purposively selected general practices (varying by deprivation, ethnicity, and setting). Questions focused on experiences of accessing/providing health care for ADHD. Reflexive thematic analysis was undertaken within a critical realist framework to understand how provision works in practice and to explore potential improvements.
In total, 20 interviews were completed with 11 HCPs and nine people with lived experience. Three themes were generated: a system under stress, incompatibility between ADHD and the healthcare system, and strategies for change in ADHD primary care provision.
Standardisation of ADHD management in primary care, providing better information and support for HCPs, and advising on reasonable adjustments for people with lived experience could help improve access to effective treatments for young people living with ADHD.
Vaginitis may be diagnosed as bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis, or coinfection. A new molecular test assays the vaginal microbiome and organisms that cause three common ...infections. The objective of the trial was to evaluate the clinical accuracy of the investigational test for vaginal swabs collected by patients (self) or clinicians. The primary and secondary outcomes were to compare the investigational test with reference methods for the three most common causes of vaginitis and compare clinician-collected with self-collected swabs.
We conducted a cross-sectional study in which women with symptoms of vaginitis were recruited at ten clinical centers and consented to the investigation between May and September 2015. The woman collected a vaginal swab, sheathed, and then handed it to the clinician. These swabs were to evaluate how self-collected swabs compared with clinician-collected swabs. The clinician collected an investigational test swab and reference test swabs. From 1,740 symptomatic patients, clinician-collected and self-collected vaginal swabs were evaluated by the molecular test and six tests. The reference methods for bacterial vaginosis were Nugent's score and Amsel's criteria for intermediate Nugent results. The reference methods for Candida infection were isolation of any potential Candida microorganisms from inoculation of two culture media: chromogenic and Sabouraud agar and sequencing. The reference methods for trichomoniasis were wet mount and culture.
For clinician-collected swabs, by reference methods, bacterial vaginosis was diagnosed in 56.5%, vaginal candidiasis in 32.8%, trichomoniasis in 8%, and none of the three infections in 24% with a coinfection rate of 20%. The investigational test sensitivity was 90.5% (95% confidence interval CI 88.3-92.2%) and specificity was 85.8% (95% CI 83.0-88.3%) for bacterial vaginosis. The investigational test sensitivity was 90.9% (95% CI 88.1-93.1%) and specificity was 94.1% (95% CI 92.6-95.4%) for the Candida group. Sensitivity for Candida glabrata was 75.9% (95% CI 57.9-87.8%) and specificity was 99.7% (95% CI 99.3-99.9%). Investigational test sensitivity was 93.1% (95% CI 87.4-96.3%) and specificity was 99.3% (95% CI 98.7-99.6%) for trichomoniasis. Results from self-collected swabs were similar to clinician-collected swabs.
A molecular-based test using vaginal swabs collected by clinicians or patients can accurately diagnose most common bacterial, fungal, and protozoan causes of vaginitis. Women and their clinicians seeking accurate diagnosis and appropriate selection of efficacious treatment for symptoms of vaginitis might benefit from this molecular test.
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