93 research outputs found

    Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood

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    The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) = 80th age-specific percentile, and (4) sucrose intake = 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (>= 2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health

    Is there warming in the pipeline? A multi-model analysis of the Zero Emissions Commitment from CO<sub>2</sub>

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    The Zero Emissions Commitment (ZEC) is the change in global mean temperature expected to occur following the cessation of net CO2 emissions and as such is a critical parameter for calculating the remaining carbon budget. The Zero Emissions Commitment Model Intercomparison Project (ZECMIP) was established to gain a better understanding of the potential magnitude and sign of ZEC, in addition to the processes that underlie this metric. A total of 18 Earth system models of both full and intermediate complexity participated in ZECMIP. All models conducted an experiment where atmospheric CO2 concentration increases exponentially until 1000 PgC has been emitted. Thereafter emissions are set to zero and models are configured to allow free evolution of atmospheric CO2 concentration. Many models conducted additional second-priority simulations with different cumulative emission totals and an alternative idealized emissions pathway with a gradual transition to zero emissions. The inter-model range of ZEC 50 years after emissions cease for the 1000 PgC experiment is −0.36 to 0.29 ∘C, with a model ensemble mean of −0.07 ∘C, median of −0.05 ∘C, and standard deviation of 0.19 ∘C. Models exhibit a wide variety of behaviours after emissions cease, with some models continuing to warm for decades to millennia and others cooling substantially. Analysis shows that both the carbon uptake by the ocean and the terrestrial biosphere are important for counteracting the warming effect from the reduction in ocean heat uptake in the decades after emissions cease. This warming effect is difficult to constrain due to high uncertainty in the efficacy of ocean heat uptake. Overall, the most likely value of ZEC on multi-decadal timescales is close to zero, consistent with previous model experiments and simple theory

    Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic

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    BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: −0.22 (95% CI: −0.30; −0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning

    STAAR: a randomised controlled trial of electronic adherence monitoring with reminder alarms and feedback to improve clinical outcomes for children with asthma

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    Background Suboptimal adherence to inhaled steroids is common in children with asthma and is associated with poor disease control, reduced quality of life and even death. Previous studies using feedback of electronically monitored adherence data have demonstrated improved adherence, but have not demonstrated a significant impact on clinical outcomes. The aim of this study was to determine whether introduction of this approach into routine practice would result in improved clinical outcomes. Methods Children with asthma aged 6–16 years were randomised to the active intervention consisting of electronic adherence monitoring with daily reminder alarms together with feedback in the clinic regarding their inhaled corticosteroid (ICS) use or to the usual care arm with adherence monitoring alone. All children had poorly controlled asthma at baseline, taking ICS and long-acting ÎČ-agonists. Subjects were seen in routine clinics every 3 months for 1 year. The primary outcome was the Asthma Control Questionnaire (ACQ) score. Secondary outcomes included adherence and markers of asthma morbidity. Results 77 of 90 children completed the study (39 interventions, 38 controls). Adherence in the intervention group was 70% vs 49% in the control group (p≀0.001). There was no significant difference in the change in ACQ, but children in the intervention group required significantly fewer courses of oral steroids (p=0.008) and fewer hospital admissions (p≀0.001). Conclusions The results indicate that electronic adherence monitoring with feedback is likely to be of significant benefit in the routine management of poorly controlled asthmatic subjects

    Inferred Biomolecular Interaction Server—a web server to analyze and predict protein interacting partners and binding sites

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    IBIS is the NCBI Inferred Biomolecular Interaction Server. This server organizes, analyzes and predicts interaction partners and locations of binding sites in proteins. IBIS provides annotations for different types of binding partners (protein, chemical, nucleic acid and peptides), and facilitates the mapping of a comprehensive biomolecular interaction network for a given protein query. IBIS reports interactions observed in experimentally determined structural complexes of a given protein, and at the same time IBIS infers binding sites/interacting partners by inspecting protein complexes formed by homologous proteins. Similar binding sites are clustered together based on their sequence and structure conservation. To emphasize biologically relevant binding sites, several algorithms are used for verification in terms of evolutionary conservation, biological importance of binding partners, size and stability of interfaces, as well as evidence from the published literature. IBIS is updated regularly and is freely accessible via http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html

    The impact of decision aids to enhance shared decision making for diabetes (the DAD study): protocol of a cluster randomized trial

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    Background. Shared decision making contributes to high quality healthcare by promoting a patientcentered approach. Patient involvement in selecting the components of a diabetes medication program that best match the patient's values and preferences may also enhance medication adherence and improve outcomes. Decision aids are tools designed to involve patients in shared decision making, but their adoption in practice has been limited. In this study, we propose to obtain a preliminary estimate of the impact of patient decision aids vs. usual care on measures of patient involvement in decision making, diabetes care processes, medication adherence, glycemic and cardiovascular risk factor control, and resource utilization. In addition, we propose to identify, describe, and explain factors that promote or inhibit the routine embedding of decision aids in practice. Methods. We will be conducting a mixed-methods study comprised of a cluster-randomized, practical, multicentered trial enrolling clinicians and their patients (n = 240) with type 2 diabetes from rural and suburban primary care practices (n = 8), with an embedded qualitative study to examine factors that influence the incorporation of decision aids into routine practice. The intervention will consist of the use of a decision aid (Statin Choice and Aspirin Choice, or Diabetes Medication Choice) during the clinical encounter. The qualitative study will include analysis of video recordings of clinical encounters and in-depth, semi-structured interviews with participating patients, clinicians, and clinic support staff, in both trial arms. Discussion. Upon completion of this trial, we will have new knowledge about the effectiveness of diabetes decision aids in these practices. We will also better understand the factors that promote or inhibit the successful implementation and normalization of medication choice decision aids in the care of chronic patients in primary care practices

    Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

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    Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

    Discrimination in lexical decision.

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    In this study we present a novel set of discrimination-based indicators of language processing derived from Naive Discriminative Learning (ndl) theory. We compare the effectiveness of these new measures with classical lexical-distributional measures-in particular, frequency counts and form similarity measures-to predict lexical decision latencies when a complete morphological segmentation of masked primes is or is not possible. Data derive from a re-analysis of a large subset of decision latencies from the English Lexicon Project, as well as from the results of two new masked priming studies. Results demonstrate the superiority of discrimination-based predictors over lexical-distributional predictors alone, across both the simple and primed lexical decision tasks. Comparable priming after masked corner and cornea type primes, across two experiments, fails to support early obligatory segmentation into morphemes as predicted by the morpho-orthographic account of reading. Results fit well with ndl theory, which, in conformity with Word and Paradigm theory, rejects the morpheme as a relevant unit of analysis. Furthermore, results indicate that readers with greater spelling proficiency and larger vocabularies make better use of orthographic priors and handle lexical competition more efficiently
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