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BACKGROUND: Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations. METHODS: In a prospective observational study, 42 children with CM were enrolled. Amino acid levels were measured at entry and at frequent intervals thereafter and consciousness was assessed by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. Logistic regression was employed using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. RESULTS: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analysed at each sampling time. CONCLUSION: Longitudinal data is provided for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation and may contribute to CM pathogenesis.

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Atmospheric fine particulate matter (PM2.5) can trigger the production of cytotoxic reactive oxygen species (ROS), which can trigger or exacerbate oxidative stress and pulmonary inflammation. We collected 111 daily (∼24 h) ambient PM2.5 samples within an urban region of North China during four seasons of 2019-2020. PM2.5 samples were examined for carbonaceous components, water-soluble ions, and elements, together with their oxidative potential (represent ROS-producing ability) by DTT assay. The seasonal peak DTTv was recorded in winter (2.86 ± 1.26 nmol min-1 m-3), whereas the DTTm was the highest in summer (40.6 ± 8.7 pmol min-1 µg-1). WSOC displayed the highest correlation with DTT activity (r = 0.84, p < 0.0001), but the influence of WSOC on the elevation of DTTv was extremely negligible. Combustion source exhibited the most significant and robust correlation with the elevation of DTTv according to the linear mixed-effects model result. Source identification investigation using positive matrix factorization displayed that combustion source (36.2%), traffic source (30.7%), secondary aerosol (15.7%), and dust (14.1%) were driving the DTTv, which were similar to the results from the multiple linear regression (MLR) analysis. Backward trajectory analysis revealed that the major air masses originate from local and regional transportation, but PM2.5 OP was more susceptible to the influence of short-distance transport clusters. Discerning the influence of chemicals on health-pertinent attributes of PM2.5, such as OP, could facilitate a deep understanding of the cause-and-effect relationship between PM2.5 and impacts.

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Montane oceanic islands possess unique geographic and ecological attributes, rendering them valuable for assessing patterns and drivers of alpha and beta taxonomic, functional, and phylogenetic diversity along elevational gradients. Such comparisons of diversity facets can provide insights into the mechanisms governing community assembly on islands. Herein, we aimed to characterize taxonomic, functional, and phylogenetic bryophyte diversity on Madeira Island within and across areas at varying elevations. We also assessed how these diversity facets for the alpha and beta components relate to ecological and anthropogenic factors. We estimated and compared alpha and beta taxonomic, functional, and phylogenetic diversity using 80 plots of 0.5 m × 0.5 m across the whole elevational gradient of the island. We compiled trait databases and supplemented them with our own observations. Phylogenetic information was sourced from the Moss and Liverwort Tree of Life. To assess the impact of ecological and anthropogenic factors on the three facets, we applied linear mixed-effects models and generalized dissimilarity models to alpha- and beta-diversity matrices, respectively. All facets of diversity exhibited strong correlations within both mosses and liverworts, indicating a substantial congruence when alpha and beta are analyzed separately. The bryophyte groups categorized by the growth form demonstrated contrasting patterns, aligning with their distinctive ecological requirements. While a mid-elevation peak emerged as a common pattern across the three facets of alpha diversity, beta diversity often displayed the opposite trend. Although the relative influence of environmental factors varied depending on the diversity facet and bryophyte grouping considered, we found that alpha and beta diversity of bryophytes are more influenced by climatic factors and the predominant type of vegetation than by anthropogenic factors. In the current context of global change, these results should be interpreted with caution, but they point to the resilience of bryophytes to survive in relatively well-preserved natural microhabitats within anthropogenic landscapes. In this study on Madeira Island, we investigated patterns and drivers of alpha and beta taxonomic, functional, and phylogenetic diversity along elevational gradients. We found that alpha and beta diversity of bryophytes are more strongly influenced by climatic factors and the predominant type of vegetation than by anthropogenic factors.

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Background: Disordered amino acid metabolism is observed in cerebral malaria (CM). We sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. We quantified 21 amino acids and coma scores longitudinally and analyzed data for associations. Methods: In a prospective observational study, we enrolled 42 children with CM. We measured amino acid levels at entry and at frequent intervals thereafter and assessed consciousness by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. We employed logistic regression using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. Results: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analyzed at each sampling time. Discussion: We provide longitudinal data for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, we propose that elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation contributing to CM pathogenesis.

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Background: Although depression is one of the most common mental health disorders outpacing other diseases and conditions, poor access to care and limited resources leave many untreated. Secure messaging (SM) offers patients an online means to bridge this gap by communicating nonurgent medical questions. We focused on self-care health management behaviors and delved into SM initiation as the initial act of engagement and SM exchanges as continuous engagement patterns. This study examined whether those with depression might be using SM more than those without depression. Methods: Patient portal data were obtained from a large academic medical center's electronic health records spanning 5 years, from January 2018 to December 2022. We organized and analyzed SM initiations and exchanges using the linear mixed-effects modeling technique. Results: Our predictors correlated with SM initiations, accounting for 25.1% of variance explained. In parallel, 24.9% of SM exchanges were attributable to these predictors. Overall, our predictors demonstrate stronger associations with SM exchanges. Discussion: We examined patients with and without depression across 2,629 zip codes over five years. Our findings reveal that the predictors affecting SM initiations and exchanges are multifaceted, with certain predictors enhancing its utilization and others impeding it. Conclusions: SM telehealth service provided support to patients with mental health needs to a greater extent than those without. By increasing access, fostering better communication, and efficiently allocating resources, telehealth services not only encourage patients to begin using SM but also promote sustained interaction through ongoing SM exchanges.

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BACKGROUND: The contact plate method is widely accepted and used in various fields where hygiene and contamination levels are crucial. Evidence regarding the applicability of the contact plate method for sampling fabric microbial contamination levels in real medical environments was limited. This study aimed to assess the applicability of the contact plate method for detecting microbial contamination on medical fabrics in a real healthcare environment, thereby providing a benchmark for fabric microbial sampling methods. METHODS: In a level three obstetrics ward of a hospital, twenty-four privacy curtains adjacent to patient beds were selected for this study. The contact plate and swab method were used to collect microbial samples from the privacy curtains on the 1st, 7th, 14th, and 28th days after they were hung. The total colony count on each privacy curtain surface was calculated, and microbial identification was performed. RESULTS: After excluding the effects of time, room type, and curtain location on the detected microbial load, the linear mixed-effects model analysis showed that contact plate method yielded lower colony counts compared to swab method (P < 0.001). However, the contact plate method isolated more microbial species than swab method (P < 0.001). 291 pathogenic strains were isolated using the contact plate method and 133 pathogenic strains were isolated via the swab method. There was no difference between the two sampling methods in the detection of gram-negative bacteria (P = 0.089). Furthermore, the microbial load on curtains in double-occupancy rooms was lower than those in triple-occupancy rooms (P = 0.021), and the microbial load on curtains near windows was lower than that near doors (P = 0.004). CONCLUSION: Contact plate method is superior to swab method in strain isolation. Swab method is more suitable for evaluating the bacterial contamination of fabrics.

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Linear mixed-effects models have been increasingly used to analyze dependent data in psychological research. Despite their many advantages over ANOVA, critical issues in their analyses remain. Due to increasing random effects and model complexity, estimation computation is demanding, and convergence becomes challenging. Applied users need help choosing appropriate methods to estimate random effects. The present Monte Carlo simulation study investigated the impacts when the restricted maximum likelihood (REML) and Bayesian estimation models were misspecified in the estimation. We also compared the performance of Akaike information criterion (AIC) and deviance information criterion (DIC) in model selection. Results showed that models neglecting the existing random effects had inflated Type I errors, unacceptable coverage, and inaccurate R-squared measures of fixed and random effects variation. Furthermore, models with redundant random effects had convergence problems, lower statistical power, and inaccurate R-squared measures for Bayesian estimation. The convergence problem is more severe for REML, while reduced power and inaccurate R-squared measures were more severe for Bayesian estimation. Notably, DIC was better than AIC in identifying the true models (especially for models including person random intercept only), improving convergence rates, and providing more accurate effect size estimates, despite AIC having higher power than DIC with 10 items and the most complicated true model.

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Microbial thermal inactivation in low moisture foods is challenging due to enhanced thermal resistance of microbes and low thermal conductivity of food matrices. In this study, we leveraged the body of previous work on this topic to model key experimental features that determine microbial thermal inactivation in low moisture foods. We identified 27 studies which contained 782 mean D-values and developed linear mixed-effect models to assess the effect of microorganism type, matrix structure and composition, water activity, temperature, and inoculation and recovery methods on cell death kinetics. Intraclass correlation statistics (I2) and conditional R2 values of the linear mixed effects models were: E. coli (R2-0.91, I2-83%), fungi (R2-0.88, I2-85%), L. monocytogenes (R2-0.84, I2-75%), Salmonella (R2-0.69, I2-46%). Finally, global response surface models (RSM) were developed to further study the non-linear effect of aw and temperature on inactivation. The fit of these models varied by organisms from R2 0.88 (E. coli) to 0.35 (fungi). Further dividing the Salmonella data into individual RSM models based on matrix structure improved model fit to R2 0.90 (paste-like products) and 0.48 (powder-like products). This indicates a negative relationship between data diversity and model performance.

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To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.

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The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure. The study included 19,128 participants from the Dongfeng-Tongji cohort's first (2013) and second (2018) follow-ups. The lung function for each subject was determined between April and December 2013 and re-assessed in 2018, with three parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) selected. The China Meteorological Data Sharing Service Center provided temperature data during the study period. In the two follow-ups, a total of 25,511 records (average age: first, 64.57; second, 65.80) were evaluated, including 10,604 males (41.57%). The inversely J-shaped associations between moving average temperatures (lag01-lag07) and FVC, FEV1, and PEF were observed, and the optimum temperatures at lag04 were 16.5 °C, 18.7 °C, and 16.2 °C, respectively. At lag04, every 1 °C increase in temperature was associated with 14.07 mL, 9.78 mL, and 62.72 mL/s increase in FVC, FEV1, and PEF in the low-temperature zone (

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OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.

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Objectives: This study aims to quantify the cross-sectional and prospective associations between quality of life (QoL) and moderate-to-vigorous physical activity (MVPA). Methods: This study was based on the Swiss children's Objectively measured PHYsical Activity cohort. The primary endpoint is the overall QoL score and its six dimensions. The main predictor is the average time spent in MVPA per day. Linear mixed effects and linear regression models respectively were used to investigate the cross-sectional and prospective associations between MVPA and QoL. Results: There were 352 participants in the study with complete data from baseline (2013-2015) and follow-up (2019). MVPA was positively associated with overall QoL and physical wellbeing (p = 0.023 and 0.002 respectively). The between-subject MVPA was positively associated with the overall QoL, physical wellbeing, and social wellbeing (p = 0.030, 0.017, and 0.028 respectively). Within-subject MVPA was positively associated with physical wellbeing and functioning at school (p = 0.039 and 0.013 respectively). Baseline MVPA was not associated with QoL 5 years later. Conclusion: Future longitudinal studies should employ shorter follow-up times and repeat measurements to assess the PA and QoL association.

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INTRODUCTION: With growing freight operations throughout the world, there is a push for transportation systems to accommodate trucks during loading and unloading operations. Currently, many urban locations do not provide loading and unloading zones, which results in trucks parking in places that obstruct bicyclist's roadway infrastructure (e.g., bicycle lanes). METHOD: To understand the implications of these truck operations, a bicycle simulation experiment was designed to evaluate the impact of commercial vehicle loading and unloading activities on safe and efficient bicycle operations in a shared urban roadway environment. A fully counterbalanced, partially randomized, factorial design was chosen to explore three independent variables: commercial vehicle loading zone (CVLZ) sizes with three levels (i.e., no CVLZ, Min CVLZ, and Max CVLZ), courier position with three levels (i.e., no courier, behind the truck, beside the truck), and with and without loading accessories. Bicyclist's physiological response and eye tracking were used as performance measures. Data were obtained from 48 participants, resulting in 864 observations in 18 experimental scenarios using linear mixed-effects models (LMM). RESULTS: Results from the LMMs suggest that loading zone size and courier position had the greatest effect on bicyclist's physiological responses. Bicyclists had approximately two peaks-per-minute higher when riding in the condition that included no CVLZ and courier on the side compared to the base conditions (i.e., Max CVLZ and no courier). Additionally, when the courier was beside the truck, bicyclist's eye fixation durations (sec) were one (s) greater than when the courier was located behind the truck, indicating that bicyclists were more alert as they passed by the courier. The presence of accessories had the lowest influence on both bicyclists' physiological response and eye tracking measures. PRACTICAL APPLICATIONS: These findings could support better roadway and CVLZ design guidelines, which will allow our urban street system to operate more efficiently, safely, and reliable for all users.

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In recent years, more attention has been paid prominently to accelerated degradation testing (ADT) in order to characterize accurate estimation of reliability properties for systems that are designed to work properly for years or even decades. In this paper, we propose optimal experimental designs for repeated measures ADTs with competing failure modes that correspond to multiple response components. The marginal degradation paths are expressed using linear mixed effects models. The optimal design is obtained by minimizing the asymptotic variance of the estimator of some quantile of the failure time distribution at the normal use conditions. Numerical examples are introduced to ensure the robustness of the proposed optimal designs and compare their efficiency with standard experimental designs.

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Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis (IPF) who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with IPF in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with IPF were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every 4 weeks. The primary endpoint was absolute change from baseline to Week 52 in FVC. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted FVC and 6-minute walk distance. Safety was monitored via adverse events. Post hoc analysis of the phase II and phase III data explored changes in FVC and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early after a prespecified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in FVC was similar between placebo and zinpentraxin alfa (-214.89 ml and -235.72 ml; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced one or more adverse events. Post hoc analysis revealed that extreme FVC decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with IPF over placebo. Learnings from this program may help improve decision making around trials in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04552899).

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This is the first study examining peer sexual harassment among 10-year-olds (N = 985), studying how being a victim, perpetrator, or witness relates to emotional problems, and how these associations are moderated by gender and class occurrence of sexual harassment. Results showed that 45% of the participants reported victimization, 17% perpetration, and 60% witnessing sexual harassment, with vast overlaps between roles. Victimization and witnessing were related to more emotional problems. Victimized girls reported more emotional problems than boys, but girls who perpetrated reported fewer emotional problems than boys. Associations between peer sexual harassment and emotional problems varied across classrooms. Our findings highlight the occurrence of peer sexual harassment in younger ages, emphasizing an ecological perspective when addressing it in school.

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This study aimed to investigate the essential role of the kicking action in front crawl. To achieve this objective, we examined the relationships of the hand propulsive force and trunk inclination with swimming velocity over a wide range of velocities from 0.75 m·s-1 to maximum effort, including the experimental conditions of arm stroke without a pull buoy. Seven male swimmers performed a 25 m front crawl at various speeds under three swimming conditions: arm stroke with a pull buoy, arm stroke without a pull buoy (AWOB) and arm stroke with a six-beat kick (SWIM). Swimming velocity, hand propulsive force and trunk inclination were calculated using an underwater motion-capture system and pressure sensors. Most notably, AWOB consistently exhibited greater values than SWIM for hand propulsive force across the range of observed velocities (p < 0.05) and for trunk inclination below the severe velocity (p < 0.05), and these differences increased with decreasing velocity. These results indicate that 1) the kicking action in front crawl has a positive effect on reducing the pressure drag acting on the trunk, thereby allowing swimmers to achieve a given velocity with less hand propulsive force, and 2) this phenomenon is significant in low-velocity ranges.

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Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

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In many psychometric applications, the relationship between the mean of an outcome and a quantitative covariate is too complex to be described by simple parametric functions; instead, flexible nonlinear relationships can be incorporated using penalized splines. Penalized splines can be conveniently represented as a linear mixed effects model (LMM), where the coefficients of the spline basis functions are random effects. The LMM representation of penalized splines makes the extension to multivariate outcomes relatively straightforward. In the LMM, no effect of the quantitative covariate on the outcome corresponds to the null hypothesis that a fixed effect and a variance component are both zero. Under the null, the usual asymptotic chi-square distribution of the likelihood ratio test for the variance component does not hold. Therefore, we propose three permutation tests for the likelihood ratio test statistic: one based on permuting the quantitative covariate, the other two based on permuting residuals. We compare via simulation the Type I error rate and power of the three permutation tests obtained from joint models for multiple outcomes, as well as a commonly used parametric test. The tests are illustrated using data from a stimulant use disorder psychosocial clinical trial.

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PURPOSE: The role of the medial olivocochlear system in speech perception in noise has been debated over the years, with studies showing mixed results. One possible reason for this could be the dependence of this relationship on the parameters used in assessing the speech perception ability (age, stimulus, and response-related variables). METHODS: The current study assessed the influence of the type of speech stimuli (monosyllables, words, and sentences), the signal-to-noise ratio (+5, 0, -5, and -10 dB), the metric used to quantify the speech perception ability (percent-correct, SNR-50, and slope of the psychometric function) and age (young vs old) on the relationship between medial olivocochlear reflex (quantified by contralateral inhibition of transient evoked otoacoustic emissions) and speech perception in noise. RESULTS: A linear mixed-effects model revealed no significant contributions of the medial olivocochlear reflex to speech perception in noise. CONCLUSION: The results suggest that there was no evidence of any modulatory influence of the indirectly measured medial olivocochlear reflex strength on speech perception in noise.

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