Linear Mixed Model Analysis Research Articles

Increase in choroidal thickness after blue light stimulation of the blind spot in young adults.

Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness. The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups. Compared with sham control (2 ± 1μm, n = 20) and red light (-1 ± 2μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60min after blue light stimulation of the blind spot (7 ± 1μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2μm, p < 0.001) but not in myopes (4 ± 2μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation. These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.

Toddlers’ Cortisol Levels in Childcare and at Home

ABSTRACT Research Findings: Measuring toddlers’ cortisol levels both in childcare and at home and their relation to child- and childcare-related factors may help to identify stress-inducing childcare practices and children who are more vulnerable to stress in childcare. Accordingly, toddlers’ (n = 320, 51.2% female, mean age = 26.8 months) cortisol levels in childcare and at home and their relation to childcare quality and child- and family-related factors were investigated using linear mixed model analyses. Mid-morning to mid-afternoon cortisol levels increased in childcare and decreased at home. Younger children had higher overall cortisol levels. Children attending groups with a higher caregiver – child ratio had slightly higher cortisol levels in childcare and slightly lower cortisol levels at home. Toddlers attending disorganized groups were considerably more stressed in childcare. Practice or Policy: The present study underlines the importance of sufficient caregiver availability and stable routines in toddler classrooms.

The Comparison of Individual and Group Hybrid Telerehabilitation Methods in Women with Urinary Incontinence.

The aim is to compare the effects of the progressive training program (PTP), a new protocol, with two different hybrid telerehabilitation methods, on the parameters related to urinary incontinence in women with urinary incontinence. A total of 50 participants with stress or mixed urinary incontinence participated in this two-arm, parallel-group, randomized, non-inferiority trial. Individual hybrid training (IHT) or group hybrid training (GHT) was given to women for 8weeks. The Power, Endurance, Repetitions, Fast contractions, and Every Contraction Timed (PERFECT) scheme and surface electromyography were used to assess pelvic floor muscle function, whereas quality of life, exercise adherence, and symptoms were assessed by questionnaires and a 3-day bladder diary. An intention-to-treat analysis was performed. Linear mixed model analysis with the factors "time" and "group" was used to determine the effects of IHT and GHT. The primary outcome was changes in pelvic floor muscle function as evaluated using the PERFECT scheme and surface electromyography at the 4th and 8th weeks relative to baseline. No statistical difference was found between the groups except for "power" of the PERFECT scheme and "nocturnal urination frequency" (p > 0.05). The GHT showed significant improvement in P and nocturnal urination frequency at the end of the 8th week (p < 0.05). From baseline to week 8, the effect size for the P value was found to be small (Cohen's d = 0.33). Eightweeks of PTP did not lead to different results in incontinence-related parameters in either of the training methods. It may be better to conduct GHT in terms of implementing PTP in incontinence and training programs in terms of time, staff workload, and applicability.

Physical activity and dexamethasone for cancer related fatigue: A preliminary placebo controlled randomized control trial.

12050 Background: Despite high frequency and significant impact on quality of life, there are limited treatment options available for cancer related fatigue (CRF) in patients with advanced cancer. The primary aim of the study was to determine the feasibility (adherence, safety, and satisfaction) of the combination therapy, physical activity (PA) plus Dexamethasone (Dex); and PA plus placebo (Pl) for CRF. The secondary aim was to explore the effects of PA+Dex, and PA+Pl on CRF as assessed by Functional Assessment of Cancer Illness Therapy–fatigue (FACIT-F). Methods: In this phase 2, randomized, double blind, placebo controlled trial, patients with advanced cancer with CRF ≥ 4/10 on Edmonton Symptom Assessment Scale were eligible. Patients were randomized to standardized PA for 4 weeks plus either 4mg of Dex (PA+Dex arm), or Pl (PA+PL arm) BID for the first 7 days. Changes in FACIT-F scores from baseline to Day 8, and Day 29 were assessed. Other outcomes included change in quality-of-life scores. Results: A total of64 (89%) patients were evaluable. The median (IQR) changes in FACIT-F scores at Day 8 and Day 29 from baseline were 9 (2,16), P&lt; 0.001; 5.75 (0,12.5), P=0.015 for PA+ Dex arm, and 3.5 (-2.13, 10), P=0.054; 6.50 (2.5, 15.5), P=0.006 for PA+ Pl arm respectively. Exploratory Linear Mixed Model (LMM) analysis showed significant treatment effect of PA +Dex, with treatment having improvement of 5.63 units for FACIT-F scores (95% Cl 1.74,9.52), P=0.005. Effect sizes for improvement of FACIT-F scores at Day 8 and Day 29 were -3.49, -2.43 in PA+Dex arm; and -1.93, -2.72 in PA+Pl arm, respectively. Effect sizes for change in fatigue related symptoms and quality of life scores as assessed by Patient-Reported Outcome Measurement Information System-Fatigue T-scores, Multidimensional Fatigue Symptom Inventory-Short Form total, and Functional Assessment of Cancer Therapy -General scores at Day 8, and Day 29 in PA+ Dex arm were 2.93 (P=0.005), 2.82 (P=0.005); 2.27 (P=0.023), 2.68 (P=0.007); -2.39 (P=0.017), -3.26 (P=0.001) respectively. Adherence to Dex and Pl were 91% and 92%, respectively, Satisfaction rates with PA+Dex and PA+Pl arms were 98% and 79%, respectively. There was no significant difference in grade ≥3 adverse events between the two arms (P = 0.36). Conclusions: Satisfaction, and tolerability to the combination therapy, and medication adherence was excellent.PA + Dex significantly improved CRF at day 8 and 29. The improvement was sustained 3 weeks after discontinuation of Dex. Further larger studies are justified. Clinical trial information: NCT03583255 .

Do trait-assessed valenced emotion motives predict valenced affective states in the daily lives of university students?

Although emotion motives have been proposed to predict momentary valenced affect experienced in everyday life, little research has been conducted on this issue. The present study examined whether trait-level hedonic and contra-hedonic emotion motives would significantly predict daily hedonic and contra-hedonic emotion goals and subsequent daily affective states. A sample of 268 university students self-reported levels of trait emotion motives in a single-occasion survey, followed by a 14-day daily diary study which assessed momentary emotion goals and affective mood states. Linear mixed model analyses showed that trait hedonic emotion motives (trying to experience positive emotions) significantly predicted corresponding daily hedonic emotion goals and subsequent higher levels of daily positive affect, while trait contra-hedonic motives (trying to experience negative emotions) evidenced an analogous pattern resulting in higher levels of daily negative affect. These findings support a bivariate rather than a bipolar relationship between hedonic and contra-hedonic motives.

Navigating the American Board of Surgery In-Training Examination (ABSITE) Success: Insights From Pre-assessment Practices in Preparing Surgical Residents for Competitive Sub-specialties.

Introduction The American Board of Surgery In-Training Examination (ABSITE) is a critical tool in assessing surgical residents' readiness for board certification and clinical practice. While various factors influencing ABSITE performance have been examined, the impact of innovative educational resources, such as TrueLearn, remains underexplored. TrueLearn's adaptive learning algorithms and comprehensive question banks offer a promising adjunct to traditional study methods. This study investigates the relationship between TrueLearn utilization and ABSITE performance among general surgery residents. Methods This retrospective study, ethically approved by the Marshall University Institutional Review Board (IRB No. 2097669-1), analyzed the performance of general surgery residents at Marshall University from 2014 to 2022. Data were collected on ABSITE scores. Additionally, quiz percentages (Quiz %) and scores from two mock exams (Exam 1 and Exam 2), all provided by the TrueLearn platform, were included in the analysis. Descriptive statistics summarized the sample characteristics. Linear mixed models were employed to examine the associations between TrueLearn engagement and ABSITE performance, accounting for the correlated nature of the data and addressing any missing data at random. Statistical analyses were conducted using the Statistical Analysis System (SAS, version 9.4; SAS Institute Inc., Cary, NC), with significance defined as a p-value < 0.05. Results The study cohort included 58 residents from 2016 to 2022. Linear mixed model analysis revealed significant positive correlations between TrueLearn Quiz %, Exam 1 scores, and Exam 2 scores with ABSITE performance. A 1% increase in Quiz % was associated with a 0.77-point rise in ABSITE scores (95% CI: 0.65, 0.89; p < 0.0001). For Exam 1, each point increase corresponded to a 6.36-point increase in ABSITE scores (95% CI: 5.01, 7.7; p < 0.0001), while Exam 2 scores showed a 3.8-point increase per point (95% CI: 2.74, 4.86; p < 0.0001). Discussion and conclusion Our findings underscore the significant impact of TrueLearn engagement on ABSITE performance, with higher quiz percentages and mock exam scores predictive of better ABSITE outcomes. This suggests that regular use of TrueLearn's educational resources enhances residents' knowledge and exam readiness. These results advocate for the integration of innovative educational tools such as TrueLearn into surgical training programs to optimize study strategies and improve exam performance. However, the study's retrospective design and single-institution focus limit the generalizability of the findings. Future research should explore these relationships in diverse settings and specialties and consider additional factors influencing ABSITE performance. This study highlights the positive association between TrueLearn utilization and ABSITE performance among general surgery residents, emphasizing the importance of innovative educational resources in surgical training. By enhancing engagement with platforms such as TrueLearn, surgical programs can improve residents' readiness for high-stakes examinations, ultimately contributing to the development of proficient surgical practitioners.

Longitudinal effects of cognitive fusion in depressive and anxious symptoms of family caregivers of people with dementia.

Family dementia caregiving has been commonly associated with psychological distress for caregivers. Cognitive fusion, that is, the tendency to become too entangled in thoughts, beliefs, or judgments (in the absence of objectivity) that may often lead to rigid thinking and impact psychological distress, is a transdiagnostic and central process of psychological inflexibility. Cross-sectional studies have shown that family caregivers of people with dementia who could present high levels of stress may be vulnerable to experiencing psychological symptoms such as depression and anxiety (even comorbidity) if they present this rigid way of thinking without seeing the objectivity of their thoughts, which could be related to aspects of the family member's dementia or helplessness in being a caregiver, for example. Specifically, studies in the caregiving field, as well as in other populations, suggest that cognitive fusion could play a mediating role in the relationship between stress and psychological symptoms. However, the predictive role of caregivers' cognitive fusion on psychological distress has not been analyzed in longitudinal studies. The objective of this study was to analyze the longitudinal effect of cognitive fusion in depressive and anxious symptoms after controlling for other relevant variables in a sample of Spanish family caregivers. Face to face assessments were conducted with a total of 176 Spanish family dementia caregivers. The study involved three assessments in a two-year period (baseline, 12 and 24 months). Linear mixed model analysis was used to analyze the associations between time-varying values of frequency and reaction to care-recipient behavioral problems, cognitive fusion, and caregivers' depressive and anxiety symptoms. Increases in cognitive fusion significantly predicted depressive and anxious symptoms (p < 0.01). In addition, reaction to care-recipients’ behavioral problems and being a female caregiver predicted increases in anxiety symptoms over time (p < 0.05). These results suggested that cognitive fusion may constitute a core dysfunctional mechanism involved in depressive and anxious symptoms. Psychological strategies aimed at reducing cognitive fusion and stress levels may be especially helpful for reducing caregivers' distress.

The Paradox of Aging-Related Fears: Fear of Loneliness in Old Age as a Motivator for Loneliness Preventive Activities

Introduction: Aging is often seen as a challenging process, prompting individuals to form emotional reactions in response to the perceived challenges associated with growing older, manifested as aging-related fears. The present study focuses on the fear of loneliness in old age, a significant concern considering the socioemotional importance of close relationships in later life. Drawing from proactive coping theory, the study explores the association between fear of loneliness and aging preparation. This research aimed to investigate whether the fear of loneliness motivates individuals to engage in activities aimed at preventing loneliness in old age. For exploratory purposes, we consider both linear and nonlinear effects at the interindividual level, as well as the intraindividual-level differences between fear levels and behavioral outcomes. In addition, we also investigate the moderating role of trait neuroticism in these associations. Methods: Data from the “Ageing as Future (AAF)” project in Germany (N = 1,183) spanning from 2012 to 2023 were utilized. A multilevel model considered both intra- and interindividual variations, incorporating time-varying variables and covariates. Results: Linear mixed model analysis revealed that increased fear of loneliness corresponded to heightened engagement in preventive activities linearly, while a quadratic term indicated an inverted U-shaped relationship. The inclusion of occasion-specific deviation scores showed that individuals were more inclined to engage in preventive activities when experiencing heightened fear of loneliness than usual. This impact of deviation in fear perception was particularly evident among those with high levels of trait neuroticism. Conclusion: The study reveals that fear of loneliness in old age is associated with proactive engagement in preventive activities, with those prone to higher levels of fear or worry being particularly affected. These results emphasize the importance of a moderate level of fear in driving action without succumbing to excessive pessimism or unrealistic optimism. The findings contribute to understanding the motivational role of aging-related fears and hold implications for gerontological practices, emphasizing the need for a balanced fear perception in addressing potential negative impacts of aging. Future research could explore moderators and long-term consequences of motivational aging-related fears.

Maintaining the validity of inference from linear mixed models in stepped-wedge cluster randomized trials under misspecified random-effects structures.

Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials. A key consideration for analyzing a stepped-wedge cluster randomized trial is accounting for the potentially complex correlation structure, which can be achieved by specifying random-effects. The simplest random effects structure is random intercept but more complex structures such as random cluster-by-period, discrete-time decay, and more recently, the random intervention structure, have been proposed. Specifying appropriate random effects in practice can be challenging: assuming more complex correlation structures may be reasonable but they are vulnerable to computational challenges. To circumvent these challenges, robust variance estimators may be applied to linear mixed models to provide consistent estimators of standard errors of fixed effect parameters in the presence of random-effects misspecification. However, there has been no empirical investigation of robust variance estimators for stepped-wedge cluster randomized trials. In this article, we review six robust variance estimators (both standard and small-sample bias-corrected robust variance estimators) that are available for linear mixed models in R, and then describe a comprehensive simulation study to examine the performance of these robust variance estimators for stepped-wedge cluster randomized trials with a continuous outcome under different data generators. For each data generator, we investigate whether the use of a robust variance estimator with either the random intercept model or the random cluster-by-period model is sufficient to provide valid statistical inference for fixed effect parameters, when these working models are subject to random-effect misspecification. Our results indicate that the random intercept and random cluster-by-period models with robust variance estimators performed adequately. The CR3 robust variance estimator (approximate jackknife) estimator, coupled with the number of clusters minus two degrees of freedom correction, consistently gave the best coverage results, but could be slightly conservative when the number of clusters was below 16. We summarize the implications of our results for the linear mixed model analysis of stepped-wedge cluster randomized trials and offer some practical recommendations on the choice of the analytic model.

Hypermethylation of BMPR2 and TGF-β Promoter Regions in Tibetan Patients with High-Altitude Polycythemia at Extreme Altitude.

Although the expression of many genes is associated with adaptation to high-altitude hypoxic environments, the role of epigenetics in the response to this harsh environmental stress is currently unclear. We explored whether abnormal DNA promoter methylation levels of six genes, namely, ABCA1, SOD2, AKT1, VEGFR2, TGF-β, and BMPR2, affect the occurrence and development of high-altitude polycythemia (HAPC) in Tibetans. The methylation levels of HAPC and the control group of 130 Tibetans from very high altitudes (> 4500m) were examined using quantitative methylation-specific real-time PCR (QMSP). Depending on the type of data, the Pearson chi-square test, Wilcoxon rank-sum test, and Fisher exact test were used to assess the differences between the two groups. The correlation between the methylation levels of each gene and the hemoglobin content was explored using a linear mixed model. Our experiment revealed that the methylation levels of the TGF-β and BMPR2 genes differed significantly in the two groups (p < 0.05) and linear mixed model analysis showed that the correlation between the hemoglobin and methylation of ABCA1, TGF-β, and BMPR2 was statistically significant (p < 0.05). Our study suggests that levels of TGF-β and BMPR2 methylation are associated with the occurrence of HAPC in extreme-altitude Tibetan populations among 6 selected genes. Epigenetics may be involved in the pathogenesis of HAPC, and future experiments could combine gene and protein levels to verify the diagnostic value of TGF-β and BMPR2 methylation levels in HAPC.

Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples.

Age-related hearing loss is the most common form of permanent hearing loss that is associated with various health traits, including Alzheimer's disease, cognitive decline, and depression. The present study aims to identify genetic comorbidities of age-related hearing loss. Past genome-wide association studies identified multiple genomic loci involved in common adult-onset health traits. Polygenic risk scores (PRS) could summarize the polygenic inheritance and quantify the genetic susceptibility of complex traits independent of trait expression. The present study conducted a PRS-based association analysis of age-related hearing difficulty in the UK Biobank sample (N = 425,240), followed by a replication analysis using hearing thresholds (HTs) and distortion-product otoacoustic emissions (DPOAEs) in 242 young adults with self-reported normal hearing. We hypothesized that young adults with genetic comorbidities associated with age-related hearing difficulty would exhibit subclinical decline in HTs and DPOAEs in both ears. A total of 111,243 participants reported age-related hearing difficulty in the UK Biobank sample (> 40years). The PRS models were derived from the polygenic risk score catalog to obtain 2627 PRS predictors across the health spectrum. HTs (0.25-16kHz) and DPOAEs (1-16kHz, L1/L2 = 65/55dB SPL, F2/F1 = 1.22) were measured on 242 young adults. Saliva-derived DNA samples were subjected to low-pass whole genome sequencing, followed by genome-wide imputation and PRS calculation. The logistic regression analyses were performed to identify PRS predictors of age-related hearing difficulty in the UK Biobank cohort. The linear mixed model analyses were performed to identify PRS predictors of HTs and DPOAEs. The PRS-based association analysis identified 977 PRS predictors across the health spectrum associated with age-related hearing difficulty. Hearing difficulty and hearing aid use PRS predictors revealed the strongest association with the age-related hearing difficulty phenotype. Youth with a higher genetic predisposition to hearing difficulty revealed a subclinical elevation in HTs and a decline in DPOAEs in both ears. PRS predictors associated with age-related hearing difficulty were enriched for mental health, lifestyle, metabolic, sleep, reproductive, digestive, respiratory, hematopoietic, and immune traits. Fifty PRS predictors belonging to various trait categories were replicated for HTs and DPOAEs in both ears. The study identified genetic comorbidities associated with age-related hearing loss across the health spectrum. Youth with a high genetic predisposition to age-related hearing difficulty and other related complex traits could exhibit sub-clinical decline in HTs and DPOAEs decades before clinically meaningful age-related hearing loss is observed. We posit that effective communication of genetic risk, promoting a healthy lifestyle, and reducing exposure to environmental risk factors at younger ages could help prevent or delay the onset of age-related hearing difficulty at older ages.

#1920 The impact of kidney function on cardiac diastolic dysfunction trajectories: insights from a longitudinal study

Abstract Background and Aims Although the association between kidney dysfunction and cardiac diastolic dysfunction has been investigated in cross-sectional studies, we currently lack a complete understanding of how the diastolic dysfunction changes over time in individuals with different kidney functions. Exploring the diastolic dysfunction trajectories is crucial as it can provide valuable insights into how kidney function influences cardiac health and which patients are at the highest cardiovascular risk. E/e’ is an echocardiography measure that estimates left ventricular filling pressure and diastolic dysfunction. This study evaluates how kidney function impacts changes in E/e′ over time. Method We identified patients from the Utrecht Patient Oriented Database (UPOD) who visited the outpatient clinic of Utrecht University Medical Center between January 2012 and April 2022. Patients who had received at least three echocardiography reports with a minimum of 12 months between them and had recorded serum creatinine measurements in their electronic health records were included. The estimated glomerular filtration rate (eGFR [mL/min/1.73 m2]) was calculated using the CKD-EPI 2021 creatinine formula without ethnicity and categorized as follows: eGFR ≥ 90, eGFR ≥ 60 - &amp;lt;90, eGFR &amp;lt; 60. Linear mixed-effect models were utilized to determine the impact of kidney function on changes in E/e′ over time. Results A total of 436 patients were included of whom 34.7% were women. The total number of echocardiography examination was 1308. Overall, the median eGFR for all patients was 78.2 mL/min/1.73 m2 [IQR: 61.9, 90.7]. Among them, 26.6%, 51.4%, and 22.0%, had an eGFR ≥ 90, eGFR ≥ 60 - &amp;lt; 90, and eGFR &amp;lt; 60, respectively. Patients with an eGFR &amp;lt; 60 had a higher prevalence of hypertension (64.6%) and cardiovascular disease (84.4%) compared to those with an eGFR ≥ 90, where the prevalence of hypertension and cardiovascular disease was 49.1% and 67.2%, respectively. Additionally, patients with an eGFR &amp;lt; 60 had the lowest mean ejection fraction of 44.9% ± 18.5% and the highest median E/e′ of 12.84 [10.10, 16.16]. The linear mixed model analysis showed that the estimated change in E/e′ per year depended on the level of kidney function. For patients with eGFR ≥ 60 - &amp;lt;90, E/e′ did not significantly change per year (p-value: 0.927). However, for patients with eGFR &amp;lt; 60, a statistically significant (p = 0.014) increase in the E/e′ of 0.45 (0.09, 0.81) was observed per year. Hypertension, diabetes mellitus, and cardiovascular disease were found to affect the change in E/e′, with estimates of 0.95 (0.41, 1.49), 1.82 (0.82, 2.89), and 1.25 (0.54, 1.97), respectively. Conclusion The trajectory of changes in E/e′ over time was significantly affected by varying levels of kidney function. Patients with impaired kidney function (eGFR &amp;lt; 60) have a higher E/e’ compared to those with normal kidney function (eGFR ≥ 90) and presented a significant increase of E/e’ per year.

Auswirkungen der visuellen Flussgeschwindigkeit auf das Radfahrerlebnis in der virtuellen Realität

AbstractApplying virtual reality to exercise has revealed mood- and performance-enhancing properties of immersive media. Social–cognitive theory and the Proteus effect suggest that avatar appearance contributes to this relation by eliciting behavioral changes. Attempting to influence exercise parameters without modifying the virtual avatar, the present study investigated the effects of differing visual flow speeds on physiological and perceived effort during aerobic exercise. Eighty-two university students participated in three separate experimental trials. During each trial, a virtual cycling track was presented at one of three velocities (16, 20, 24 km/h) in counterbalanced order, while participants cycled at a moderate intensity for 20 min. Objective and subjective measures of effort and affective states were recorded every five minutes. With increasing visual flow speed, a linear decrease of heart rate, perceived effort, and arousal and a linear increase of valence were expected. Mixed linear model analyses revealed no significant main effect of visual flow speed on any dependent variable. A nonlinear relation between visual flow speed and heart rate was identified through pairwise comparisons between visual flow conditions.

Hemoglobin A1c Trajectories During Pregnancy and Adverse Outcomes in Women With Type 2 Diabetes: A Danish National Population-Based Cohort Study.

To identify and characterize groups of pregnant women with type 2 diabetes with distinct hemoglobin A1c (HbA1c) trajectories across gestation and to examine the association with adverse obstetric and perinatal outcomes. This was a retrospective Danish national cohort study including all singleton pregnancies in women with type 2 diabetes, giving birth to a liveborn infant, between 2004 and 2019. HbA1c trajectories were identified using latent class linear mixed-model analysis. Associations with adverse outcomes were examined with logistic regression models. A total of 1,129 pregnancies were included. Three HbA1c trajectory groups were identified and named according to the glycemic control in early pregnancy (good, 59%; moderate, 32%; and poor, 9%). According to the model, all groups attained an estimated HbA1c <6.5% (48 mmol/mol) during pregnancy, with no differences between groups in the 3rd trimester. Women with poor glycemic control in early pregnancy had lower odds of having an infant with large-for-gestational-age (LGA) birth weight (adjusted odds ratio [aOR] 0.57, 95% CI 0.40-0.83), and higher odds of having an infant with small-for-gestational age (SGA) birth weight (aOR 2.49, 95% CI 2.00-3.10) and congenital malformation (CM) (aOR 4.60 95% CI 3.39-6.26) compared with women with good glycemic control. There was no evidence of a difference in odds of preeclampsia, preterm birth, and caesarean section between groups. Women with poor glycemic control in early pregnancy have lower odds of having an infant with LGA birth weight, but higher odds of having an infant with SGA birth weight and CM.

Effects of Speech Characteristics on Electroglottographic and Instrumental Acoustic Voice Analysis Metrics in Women With Structural Dysphonia Before and After Treatment.

Literature suggests a dependency of the acoustic metrics, smoothed cepstral peak prominence (CPPS) and harmonics-to-noise ratio (HNR), on human voice loudness and fundamental frequency (F0). Even though this has been explained with different oscillatory patterns of the vocal folds, so far, it has not been specifically investigated. In the present work, the influence of three elicitation levels, calibrated sound pressure level (SPL), F0 and vowel on the electroglottographic (EGG) and time-differentiated EGG (dEGG) metrics hybrid open quotient (OQ), dEGG OQ and peak dEGG, as well as on the acoustic metrics CPPS and HNR, was examined, and their suitability for voice assessment was evaluated. In a retrospective study, 29 women with a mean age of 25 years (± 8.9, range: 18-53) diagnosed with structural vocal fold pathologies were examined before and after voice therapy or phonosurgery. Both acoustic and EGG signals were recorded simultaneously during the phonation of the sustained vowels /ɑ/, /i/, and /u/ at three elicited levels of loudness (soft/comfortable/loud) and unconstrained F0 conditions. A linear mixed-model analysis showed a significant effect of elicitation effort levels on peak dEGG, HNR, and CPPS (all p < .01). Calibrated SPL significantly influenced HNR and CPPS (both p < .01). Furthermore, F0 had a significant effect on peak dEGG and CPPS (p < .0001). All metrics showed significant changes with regard to vowel (all p < .05). However, the treatment had no effect on the examined metrics, regardless of the treatment type (surgery vs. voice therapy). The value of the investigated metrics for voice assessment purposes when sampled without sufficient control of SPL and F0 is limited, in that they are significantly influenced by the phonatory context, be it speech or elicited sustained vowels. Future studies should explore the diagnostic value of new data collation approaches such as voice mapping, which take SPL and F0 effects into account.

Evaluation of completely online psychotherapy with app-support versus therapy as usual for clients with depression or anxiety disorder: A retrospective matched cohort study investigating the effectiveness, efficiency, client satisfaction, and costs

IntroductionDepressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are looking for modern ways of therapy. Online psychotherapy is a promising option for better meeting clients’ needs. Recently, a new psychotherapy concept has emerged that combines videoconferencing sessions with support through a mobile application. The latter allows for ecological momentary assessments and interventions, facilitates communication between patients and therapists in between sessions through chat, and allows for incorporating feedback-informed treatment principles. Material and methodsThe study was a retrospective observational matched cohort study, comparing online psychotherapy with Therapy As Usual (TAU) for clients with depressive or anxiety disorders. Data were obtained via questionnaires, which are part of standard clinical care. Primary outcomes included general mental functioning, and symptoms of depression and anxiety. Secondary outcomes were efficiency, client satisfaction, and therapy costs. Primary endpoints were analyzed using linear mixed models analysis, with an interaction term between time and group. Secondary outcomes were analyzed using linear regression. ResultsLarger improvements were observed in the online compared to the TAU group for general mental functioning and depressive disorder (i.e., General mental functioning: B = -8.50, 95 CI: −15.01 − −1.97, p = 0.011; Depressive disorder: B = − 3.66, 95 % CI: −5.79 – -1.54p < 0.01). No significant differences in change over time between the two groups were observed for anxiety disorder (B = -3.64, 95 % CI: (−13.10 – 5.82) p = 0.447). The total number of sessions was significantly higher in the online psychotherapy group than in TAU (B = 3.71, p < 0.01), although clients were matched on treatment time in weeks. Treatment session duration in minutes was comparable across the groups. DiscussionOnline psychotherapy with app support showed to be a promising alternative to TAU for depressive and anxiety disorders. More research is needed to evaluate the effectiveness, cost-effectiveness and client satisfaction of online psychotherapy compared to TAU, such as randomized controlled trials or studies multiple baseline series designs, and in-depth qualitative research.

Effectiveness of a self-help guide during a temporary alcohol abstinence challenge: a randomized controlled trial.

The popularity of temporary abstinence challenges (TACs) concerning alcohol consumption is increasing. Support is found to be essential for participants to help them get through a challenge. This study aimed to evaluate the additional effect of a self-help guide, based on health behaviour theories and behaviour change techniques, on (i) successful completion of a TAC and (ii) changes in drinking refusal self-efficacy (DRSE), behavioural automaticity, craving, and alcohol consumption. A randomized controlled trial was performed (OSF registries: OSF.IO/B95VU). NoThanks participants received a questionnaire before the TAC (T0) and 8months after the TAC (T1). Out of a subgroup of 1308 respondents who were interested in additional support, 652 were randomly assigned to receive the guide (experimental group), and 656 did not receive any additional support (control group). Logistic regressions and (generalized) linear mixed model analyses were used. After 8months, all participants showed a significant decrease in behavioural automaticity, craving, and alcohol consumption, irrespective of group assignment. No significant changes were observed in the DRSE. This degree of change over time in behavioural automaticity, craving, and alcohol consumption did not differ between the experimental and control group. Sensitivity analyses with participants in the experimental group, who differed in exposure to the guide, did not show differences either. The self-help guide, and how it was designed, added no value to the TAC. Future research should focus on more bottom-up, customized support and explore what (different subgroups of) participants think they need as extra support during a TAC.

Influence of climate, soil and vegetation diversity on the leaf area index as measured by canopy hemispherical photography in tropical rainforests across a wide elevational gradient

Tropical rainforests (TRFs) play an important role in regulating the global climate and conserving biodiversity. Leaf area index (LAI) determines the capacity of TRFs for radiation interception and carbon sequestration via photosynthesis while also influencing the water loss from TRF canopies via transpiration. Elevational gradients in tropical environments provide an approach to investigate the influence of environmental variations on key vegetation properties such as the LAI. In this work we determined the concurrent, interactive influences of the elevational gradients of the environment (i.e. selected climatic and soil properties) and vegetation (tree diversity and structure) in determining the variation of LAI of one-hectare permanent sampling plots (PSPs) within TRFs across a wide elevational gradient (from 117 m to 2132 m above sea level). Eight rounds of canopy hemispherical photography were carried out at three-month intervals over a 24-month period from 2019 to 2022. Canopy LAI was estimated using HemiView image processing software. Long-term mean climatic data from 1990 to 2021 were extracted for the PSPs from monthly global weather database of CRU-TS-4.06-bias corrected with WorldClim-2.1. Key soil properties were measured at 0–15 cm and 15–30 cm depths via soil sampling. Tree diversity was determined by a complete census of all trees with equal or greater than 10 cm in diameter at breast height. Total tree biomass was estimated using allometric equations. Linear mixed model analysis of LAI showed significant (p < 0.05) variance for the random effects of elevation and elevation × time interaction. In a majority of measurement rounds, variance of LAI due to elevation was significant while at a majority of elevations, the fixed effect of measurement round on LAI was significant. Leaf area index showed significant linear reductions with elevation in all rounds, at rates ranging from 0.175 to 0.357 per 1000 m. Linear and multiple regression analyses identified increasing maximum cumulative soil water deficit, CSWDMax (an index of water deficit computed as the difference between evapotranspiration and precipitation), as the major climatic factor responsible for the reduction of LAI with elevation. Decreasing solar irradiance (SR) and increasing day-night temperature difference (DTR) with elevation also contributed to the observed LAI trend. Multiple regression analysis showed soil exchangeable potassium (KEx) and available phosphorus (PAv) influencing LAI positively while electrical conductivity (EC) and total nitrogen (NTot) influencing LAI negatively. Variation of Shannon-Wiener tree diversity index (H) and total tree biomass per hectare (TBM) contributed positively to the observed elevational variation of LAI. Factor analysis extracted two underlying factor constructs which accounted for 86 % of the combined variation in climate, soil and vegetation across the elevational gradient. Plot-wise scores of Factor 1, which had CSWDMax, SR, DTR, soil EC, NTot and H loading strongly and accounting for 70 % of the variation, showed a significant linear relationship with LAI. A cluster analysis incorporating the elevational variation of LAI, climate, soil and vegetation clearly classified the TRFs into four ranges of elevation at a linkage distance of 0.75. We conclude that LAI of TRFs in our study decreases with increasing elevation and identify increasing water deficits with elevation as the major climatic factor controlling this reduction.

Transcranial Alternating Current Stimulation over Frontal Eye Fields Mimics Attentional Modulation of Visual Processing.

Attentional control over sensory processing has been linked to neural alpha oscillations and related inhibition of cerebral cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in frontal eye fields (FEFs) are causally involved in the top-down regulation of visual processing in humans (male and female). We applied sham-controlled, intermittent transcranial alternating current stimulation (tACS) over bilateral FEF at either 10 Hz (alpha) or 40 Hz (gamma) to manipulate attentional preparation in a visual discrimination task. Under each stimulation condition, we measured psychometric functions for contrast perception and introduced a novel linear mixed modeling approach for statistical control of neurosensory side effects of the electric stimulation. tACS at alpha frequency reduced the slope of the psychometric function, resulting in improved subthreshold and impaired superthreshold contrast perception. Side effects on the psychometric functions were complex and showed large interindividual variability. Controlling for the impact of side effects on the psychometric parameters by using covariates in the linear mixed model analysis reduced this variability and strengthened the perceptual effect. We propose that alpha tACS over FEF mimicked a state of endogenous attention by strengthening a fronto-occipitoparietal network in the alpha band. We speculate that this network modulation enhanced phasic gating in occipitoparietal cortex leading to increased variability of single-trial psychometric thresholds, measurable as a reduction of psychometric slope.

Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age: A Longitudinal Birth Cohort Study

Introduction: Few studies have investigated the association between frailty and subsequent body composition. Methods: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. Results: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with “stable frailty,” followed by those with “increasing frailty” experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group “stable not frail.” Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third. Conclusions: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.