Dosing time matters.
Ontology highlight
ABSTRACT:
SUBMITTER: Ruben MD
PROVIDER: S-EPMC8011856 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In this study, we investigated whether working memory capacity (WMC), personality characteristics (grit) and number of matches played (time on task) can predict performance score (matchmaking rating [MMR]) in experienced players of a popular video game called Dota 2. A questionnaire and four online-based cognitive tasks were used to gather the data, and structural equation modelling (SEM) was used to investigate the interrelationships between constructs. The results showed that time on task was the strongest predictor of MMR, and grit also significantly influenced performance. However, WMC did not play a substantial role in predicting performance while playing Dota 2. These results are discussed in relation to sample characteristics and the role of deliberate practice and skill acquisition within the domain of playing Dota 2. Further, we suggest that future research investigates the social aspects of attaining skill, the relationship between personality and performance, and the qualitative aspects of time spent on a task.
| S-EPMC6205640 | biostudies-literature
Project description:BACKGROUND:New polymorphism datasets from heterochroneous data have arisen thanks to recent advances in experimental and microbial molecular evolution, and the sequencing of ancient DNA (aDNA). However, classical tools for population genetics analyses do not take into account heterochrony between subsets, despite potential bias on neutrality and population structure tests. Here, we characterize the extent of such possible biases using serial coalescent simulations. METHODOLOGY/PRINCIPAL FINDINGS:We first use a coalescent framework to generate datasets assuming no or different levels of heterochrony and contrast most classical population genetic statistics. We show that even weak levels of heterochrony ( approximately 10% of the average depth of a standard population tree) affect the distribution of polymorphism substantially, leading to overestimate the level of polymorphism theta, to star like trees, with an excess of rare mutations and a deficit of linkage disequilibrium, which are the hallmark of e.g. population expansion (possibly after a drastic bottleneck). Substantial departures of the tests are detected in the opposite direction for more heterochroneous and equilibrated datasets, with balanced trees mimicking in particular population contraction, balancing selection, and population differentiation. We therefore introduce simple corrections to classical estimators of polymorphism and of the genetic distance between populations, in order to remove heterochrony-driven bias. Finally, we show that these effects do occur on real aDNA datasets, taking advantage of the currently available sequence data for Cave Bears (Ursus spelaeus), for which large mtDNA haplotypes have been reported over a substantial time period (22-130 thousand years ago (KYA)). CONCLUSIONS/SIGNIFICANCE:Considering serial sampling changed the conclusion of several tests, indicating that neglecting heterochrony could provide significant support for false past history of populations and inappropriate conservation decisions. We therefore argue for systematically considering heterochroneous models when analyzing heterochroneous samples covering a large time scale.
| S-EPMC2678253 | biostudies-literature
Project description:Mitigating climate change to achieve the goal of staying below 2 °C of warming requires urgent reductions of emissions. Demand-side measures mostly focus on the footprints of consumption. Analysing time use can add to understand the carbon implications of everyday life and the potentials and limitations for decarbonising consumption better. We investigate the carbon footprints of everyday activities in Austria. We linked data from the Austrian Time-use Survey and the Austrian Household Budget Survey with the Eora-MRIO for 2009-2010 in order to estimate the household carbon footprints of all time-use activities. We introduce a functional time-use perspective differentiating personal, committed, contracted and free time to investigate the average carbon intensity of activities per hour, for an average day and for the average woman and man. We find that personal time is relatively low-carbon, while household as well as leisure activities show large variation in terms of CO2e footprint/h. The traditional gendered division of labour shapes the time-use patterns of women and men, with implications for their carbon footprints. Further research analysing differences in household size, income, location and availability of infrastructure in their relation to time use is crucial to be able to assess possible pathways towards low carbon everyday life.
| S-EPMC6686204 | biostudies-literature
Project description:Studies suggest that bedtime dosing of an angiotensin-converting enzyme (ACE)-inhibitor or angiotensin receptor blocker shows a more sustained and consistent 24-h antihypertensive profile, including greater night-time blood pressure (BP) reduction. We compared the antihypertensive effects of morning (a.m.) and evening (p.m.) dosing of valsartan on 24-h BP.This 26-week, multicentre, randomized, double-blind study evaluated the efficacy and safety of valsartan 320?mg, dosed a.m. or p.m., versus lisinopril 40?mg (a.m.), a long-acting ACE-inhibitor, in patients with grade 1-2 hypertension and at least one additional cardiovascular risk factor. Patients (n?=?1093; BP?=?156?±?11/91?±?8?mmHg; 62 years, 56% male, 99% white) received (1?:?1?:?1) valsartan 160?mg a.m. or p.m. or lisinopril 20?mg a.m. for 4 weeks, then force-titrated to double the initial dose for 8 weeks. At Week 12, hydrochlorothiazide (HCTZ) 12.5?mg was added for 14 weeks if office BP was more than 140/90?mmHg and/or ambulatory BP more than 130/80?mmHg.Mean 24-h ambulatory SBP change from baseline to Weeks 12 and 26 was comparable between valsartan a.m. (-10.6 and -13.3?mmHg) and p.m. (-9.8 and -12.3?mmHg) and lisinopril (-10.7 and -13.7?mmHg). There was no benefit of valsartan p.m. versus a.m. on night-time BP, early morning BP and morning BP surge. Evening dosing also did not improve BP lowering in patients requiring add-on HCTZ or in nondippers at baseline. All treatments were well tolerated.Once-daily dosing of valsartan 320?mg results in equally effective 24-h BP efficacy, regardless of dosing time.ClinicalTrials.gov Identifier: NCT00241124.
| S-EPMC4284009 | biostudies-literature
Project description:The ratio of divergence at nonsynonymous and synonymous sites, dN/dS, is a widely used measure in evolutionary genetic studies to investigate the extent to which selection modulates gene sequence evolution. Originally tailored to codon sequences of distantly related lineages, dN/dS represents the ratio of fixed nonsynonymous to synonymous differences. The impact of ancestral and lineage-specific polymorphisms on dN/dS, which we here show to be substantial for closely related lineages, is generally neglected in estimation techniques of dN/dS. To address this issue, we formulate a codon model that is firmly anchored in population genetic theory, derive analytical expressions for the dN/dS measure by Poisson random field approximation in a Markovian framework and validate the derivations by simulations. In good agreement, simulations and analytical derivations demonstrate that dN/dS is biased by polymorphisms at short time scales and that it can take substantial time for the expected value to settle at its time limit where only fixed differences are considered. We further show that in any attempt to estimate the dN/dS ratio from empirical data the effect of the intrinsic fluctuations of a ratio of stochastic variables, can even under neutrality yield extreme values of dN/dS at short time scales or in regions of low mutation rate. Taken together, our results have significant implications for the interpretation of dN/dS estimates, the McDonald-Kreitman test and other related statistics, in particular for closely related lineages.
| S-EPMC3879453 | biostudies-literature
Project description:ObjectiveMitochondrial capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates heart metabolism through cardiomyocyte-autonomous mechanisms. While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism in normal and obese skeletal muscle. However, the effects of glucocorticoid intermittence on heart metabolism and heart failure remain unknown. Here we investigated the extent to which circadian time of dosing regulates the effects of the glucocorticoid prednisone in heart metabolism and function in conditions of single pulse or chronic intermittent dosing.Methods and resultsIn WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The drug effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted glucocorticoid receptor (GR) ablation, and depended on an intact cardiomyocyte clock, as shown by inducible cardiomyocyte-restricted ablation of Brain and Muscle ARNT-like 1 (BMAL1). Conjugating time-of-dosing with chronic intermittence, we found that once-weekly prednisone improved metabolism and function in heart after myocardial injury dependent on circadian time of intake, i.e. with light-phase but not dark-phase dosing.ConclusionsOur study identifies cardiac-autonomous mechanisms through which circadian-specific intermittent dosing reconverts glucocorticoid drugs to metabolic boosters for the heart.
| S-EPMC9243158 | biostudies-literature
Project description:Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ?18 years who received ?2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7?µg/mL (P?<?.001), which temporally coincided with recommendations published by the Infectious Disease Society of America that recommend targeting higher trough concentrations. Two or more abnormally low trough concentrations were accompanied by an increase in the dose 75% of the time. Similarly, ?2 abnormally high trough concentrations were followed by a decrease in the dose 35% of the time. In aggregate, these data suggest that vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen.
| S-EPMC5641452 | biostudies-literature
Project description:BackgroundThis systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.MethodsWe conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAdult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15-20 μg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality.ConclusionsWe identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.
| S-EPMC7866743 | biostudies-literature
Project description:Background:Extensive knowledge on the genetic characterization of marine organisms has been assembled, mainly concerning the spatial distribution and structuring of populations. Temporal monitoring assesses not only the stability in genetic composition but also its trajectory over time, providing critical information for the accurate forecast of changes in genetic diversity of marine populations, particularly important for both fisheries and endangered species management. We assessed fluctuations in genetic composition among different sampling periods in the western Portuguese shore in three fish species. Methods:White seabream Diplodus sargus, sand smelt Atherina presbyter and shanny Lipophrys pholis were chosen, because of their genetic patterns in distinct ecological environments, insight into historical and contemporary factors influencing population effective size (N e ), and degree of commercial exploitation. Samples were obtained near Lisbon between 2003 and 2014 and screened for genetic variation with mitochondrial and nuclear markers. Analyses included genealogies, genetic diversities, temporal structures and contemporary N e . Results:For mtDNA no temporal structure was detected, while for nDNA significant differences were recorded between some sampling periods for the shanny and the sand smelt. Haplotype networks revealed deep genealogies, with various levels of diversification. The shanny revealed a smaller N e /generation when compared to the other species, which, in turn, revealed no evidence of genetic drift for most study periods. These results highlight the fact that temporal variations in genetic pool composition should be considered when evaluating the population structure of fish species with long distance dispersal, which are more vulnerable to recruitment fluctuations.
| S-EPMC7197400 | biostudies-literature
Project description:The Toxicogenomics Project was a 5-year collaborative project (2002-2007) by a consortium comprising the Japanese government and several pharmaceutical companies. The project produced the 'Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system' (TG-GATEs), a large-scale database of transcriptomics and pathology data potentially useful for predicting the toxicity of new chemical entities. Conventional in vivo toxicology data was collected from single dose and repeat dosing studies on rats, and gene expression measured for the liver (and kidney in some cases). To provide information on species differences, gene expression was also measured in rat and human hepatocytes treated with the chemicals in vitro. Approximately 130 chemicals, primarily medicinal compounds, were tested at multipe doses. Gene expression was analysed using Affymetrix GeneChip arrays. The gene expression data has been submitted in four parts: in vivo single dose (E-MTAB-799), in vivo repeat dosing, in vitro rat (E-MTAB-797) and in vitro human (E-MTAB-798). This submission comprises the in vivo, repeat dosing studies. If publishing results based on this data, please cite the full project name 'Toxicogenomics Project and Toxicogenomics Informatics Project', the database name 'Open TG-GATEs' and the URL 'http://toxico.nibio.go.jp'. Please note that the European Bioinformatics Institute (EBI) was not involved in the Toxicogenomics Project in any way, acting only to submit the transcriptomics data to Array Express. Queries about the project can be addressed to the consortium directly via 'opentggates@nibio.go.jp'. This dataset is part of the TransQST collection.
2012-02-10 | E-MTAB-800 | biostudies-arrayexpress