Linear Mixed-effects Models Research Articles

Endpoints and Design for Clinical Trials in USH2A-Related Retinal Degeneration: Results and Recommendations From the RUSH2A Natural History Study.

To evaluate functional and structural assessments as endpoints for clinical trials for USH2A-related retinal degeneration. People with biallelic disease-causing variants in USH2A, visual acuity ≥ 20/80, and visual field ≥ 10° diameter were enrolled in a 4-year, natural history study. Participants underwent static perimetry, microperimetry, visual acuity, fullfield stimulus testing (FST), and optical coherence tomography annually. Rates of change estimated from mixed-effects linear models and percentages of eyes with changes exceeding the coefficient of repeatability (CoR) or thresholds conforming with U.S. Food and Drug Administration (FDA) guidelines were evaluated. Rates of change were generally more sensitive to change than proportions of eyes exceeding a threshold such as the CoR. Baseline ellipsoid zone area ≥ 3mm2 was necessary to detect change. Mean sensitivity and volumetric hill of vision measures on static perimetry had similar properties and were the most sensitive to changes of the continuous measures. The highest 4-year proportions of eyes exceeding the CoR were from FST testing (47%) and microperimetry (32%). Specification of loci as functional transition points (FTPs) resulted in 45% (static perimetry) and 46% (microperimetry) at 4years, meeting FDA guidelines for progression. Rate of change of mean sensitivity on static perimetry was a sensitive perimetric continuous measure. Percentages of within-eye change were largest with FST testing and microperimetry. FTPs appear to be particularly sensitive to change. These results affect clinical trial design for USH2A-related retinal degeneration. Analyses of natural history data from the Rate of Progression in USH2A-Related Retinal Degeneration (RUSH2A) study can inform eligibility criteria and endpoints for clinical trials.

Comparison of Diffusion-weighted MRI using Singe-Shot Echo-planar Imaging (SS-EPI) and Split Acquisition of Fast Spin Echo Signal (SPLICE) Imaging, a non-EPI technique, in Tumors of the Head and Neck.

Diffusion-weighted imaging (DWI) using single-shot echo planar imaging (DW-EPI) is susceptible to distortions around air-filled cavities and dental fillings, typical for the head and neck area. Non-EPI, Split acquisition of fast spin echo signals for diffusion imaging (DWSPLICE) could reduce these distortions and enhance image quality, thereby potentially improving recurrence assessment in squamous cell carcinoma (SCC) of the head and neck region. This study evaluated whether DW-SPLICE is a viable alternative to DW-EPI through quantitative and qualitative analyses. The DW-SPLICE sequence was incorporated into the standard 3.0T head and neck MRI protocol with DW-EPI. Retrospective analysis was conducted on two subgroups: firstly benign or malignant lesions, and secondly post-treatment SCC recurrence. In both subgroups Image quality and distortion were scored by two independent radiologists, blinded for DW-technique, and evaluated using mixed-effect linear models. Lesion apparent diffusion coefficient (ADC) values were assessed with inter-class correlation (ICC) and Bland-Altman analyses. DWI's delineation geometric similarity to T1-weighted post-contrast (T1Wc) MRI was evaluated using the Dice Similarity Coefficient (DSC) before and after registration. Recurrence in post-treatment SCC scans was evaluated by the same two radiologists blinded for DW-technique. Recurrence detection rates were then compared between DW-SPLICE and DW-EPI using mixed logistic regression at six months and at one-year post-scan follow-up data. From August 2020 to January 2022, 55 benign or malignant lesion scans (55 patients) and 74 post-treatment SCC scans (66 patients) were analyzed. DW-SPLICE scored better on image quality and showed less overall distortion than DW-EPI (0.04<p<0.001). There was high ADC measurement reliability (ICC=0.93, p<0.001), though a proportional bias was also observed (β=0.11, p=0.03), indicating the bias increases as ADC values rise. DWSPLICE exhibited greater geometric similarity to T1Wc before registration (DSC 0.63 vs 0.47, p<0.001) and outperformed DW-EPI by more accurately identifying recurrences after one year (OR=0.96, p=0.05) but not after six months (OR=0.72, p=0.13). DW-SPLICE surpasses DW-EPI on image distortion and quality and improves diagnostic reliability for detecting recurrent or residual SCC on 3T MRI of the HN. Consistent use of one method for follow-up is advised, as ADC values are not completely interchangeable. Integrating DW-SPLICE can significantly improve tumor assessments in clinical practice. ANTs = Advanced Normalization Tools; DSC = Dice Similarity Coefficient; DW-EPI = Diffusion-weighted single-shot echo planar imaging; DW-MS-EPI = Diffusion-weighted multi-shot echo planar imaging; DW-SPLICE = Diffusion-weighted split acquisition of fast spin echo signals for diffusion imaging; DW-TSE = Diffusion-weighted Turbo Spin Echo; ICC = Intraclass Correlation Coefficient; ROC = Receiver Operating Characteristic; SCC = Squamous cell carcinoma; T1WIc = T1 weighted imaging with gadolinium contrast.

Investigating cross-sectional and longitudinal relationships between brain structure and distinct dimensions of externalizing psychopathology in the ABCD sample.

Externalizing psychopathology in childhood is a predictor of poor outcomes across the lifespan. Children exhibiting elevated externalizing symptoms also commonly show emotion dysregulation and callous-unemotional (CU) traits. Examining cross-sectional and longitudinal neural correlates across dimensions linked to externalizing psychopathology during childhood may clarify shared or distinct neurobiological vulnerability for psychopathological impairment later in life. We used tabulated brain structure and behavioural data from baseline, year 1, and year 2 timepoints of the Adolescent Brain Cognitive Development Study (ABCD; baseline n = 10,534). We fit separate linear mixed effect models to examine whether baseline brain structures in frontolimbic and striatal regions (cortical thickness or subcortical volume) were associated with externalizing symptoms, emotion dysregulation, and/or CU traits at baseline and over a two-year period. The most robust relationships found at the cross-sectional level was between cortical thickness in the right rostral middle frontal gyrus and bilateral pars orbitalis was positively associated with CU traits (β = |0.027-0.033|, pcorrected = 0.009-0.03). Over the two-year follow-up period, higher baseline cortical thickness in the left pars triangularis and rostral middle frontal gyrus predicted greater decreases in externalizing symptoms ((F = 6.33-6.94, pcorrected = 0.014). The results of the current study suggest that unique regions within frontolimbic and striatal networks may be more strongly associated with different dimensions of externalizing psychopathology. The longitudinal findings indicate that brain structure in early childhood may provide insight into structural features that influence behaviour over time.

Mlambe economic and relationship-strengthening intervention for alcohol use decreases violence and improves relationship quality in couples living with HIV in Malawi

IntroductionA syndemic of unhealthy alcohol use, intimate partner violence (IPV), and economic insecurity threatens to derail progress towards UNAIDS 95-95-95 targets in sub-Saharan Africa. We developed a combined economic and relationship-strengthening intervention called Mlambe to reduce unhealthy alcohol use and increase adherence to antiretroviral therapy for couples in Malawi. This study evaluates the additional impact of Mlambe on IPV and relationship dynamics. MethodsIn a pilot randomized controlled trial, 78 married couples (156 individuals) living with HIV and reporting unhealthy alcohol use based on the AUDIT-C (at least one partner) were recruited from HIV care clinics in Zomba, Malawi. The intervention arm (39 couples) received a 10-month program consisting of incentivized savings accounts with financial literacy education, relationship education, and couples counseling sessions to build relationship skills. The control arm (39 couples) received enhanced usual care (EUC) with brief alcohol counseling. We used linear mixed-effects models to assess the effects of Mlambe on relationship quality (e.g., constructive communication, unity, sexual satisfaction) and IPV (physical, sexual, and emotional) by including fixed effects for treatment arm and a random effect for dyad, and tested whether effects on IPV and relationship quality differed by gender. ResultsAt 10- and 15-month follow-up visits, couples in the Mlambe arm showed greater increases in couple communication, unity, sexual satisfaction, intimacy, and trust (Cohen's d ranged from 0.36 to 0.56; p < 0.05) as compared to EUC. Couples in the Mlambe arm also showed significant decreases in physical and emotional IPV (Cohen's d ranged from 0.33 to 0.49; p < 0.05) as compared to EUC. Subsequent moderation analyses indicated that women reported significantly greater improvements in relationship quality than men, except for sexual satisfaction (p < 0.05), and greater declines in physical IPV than men (p < 0.05). ConclusionsMlambe resulted in significant improvements in relationship quality and decreased IPV in couples, particularly for women who as a group reported lower relationship quality at baseline. Economic and relationship-strengthening interventions have potential to disrupt harmful syndemics of violence, substance use, and poverty among couples living with HIV. Clinical trial numberNCT#04906616.

Acoustic and Kinematic Predictors of Intelligibility and Articulatory Precision in Parkinson's Disease.

This study investigated relationships within and between perceptual, acoustic, and kinematic measures in speakers with and without dysarthria due to Parkinson's disease (PD) across different clarity conditions. Additionally, the study assessed the predictive capabilities of selected acoustic and kinematic measures for intelligibility and articulatory precision ratings. Forty participants, comprising 22 with PD and 18 controls, read three phrases aloud using conversational, less clear, and more clear speaking conditions. Acoustic measures and their theoretical kinematic parallel measures (i.e., acoustic and kinematic distance and vowel space area [VSA]; second formant frequency [F2] slope and kinematic speed) were obtained from the diphthong /aɪ/ and selected vowels in the sentences. A total of 368 listeners from crowdsourcing provided ratings for intelligibility and articulatory precision. The research questions were examined using correlations and linear mixed-effects models. Intelligibility and articulatory precision ratings were highly correlated across all speakers. Acoustic and kinematic distance, as well as F2 slope and kinematic speed, showed moderately positive correlations. In contrast, acoustic and kinematic VSA exhibited no correlation. Among all measures, acoustic VSA and kinematic distance were robust predictors of both intelligibility and articulatory precision ratings, but they were stronger predictors of articulatory precision. The findings highlight the importance of measurement selection when examining cross-domain relationships. Additionally, they support the use of behavioral modifications aimed at eliciting larger articulatory gestures to improve intelligibility in individuals with dysarthria due to PD. https://doi.org/10.23641/asha.27011281.

Effectiveness of a Digital Health Intervention Leveraging Reinforcement Learning: Results From the Diabetes and Mental Health Adaptive Notification Tracking and Evaluation (DIAMANTE) Randomized Clinical Trial.

Digital and mobile health interventions using personalization via reinforcement learning algorithms have the potential to reach large number of people to support physical activity and help manage diabetes and depression in daily life. The Diabetes and Mental Health Adaptive Notification and Tracking Evaluation (DIAMANTE) study tested whether a digital physical activity intervention using personalized text messaging via reinforcement learning algorithms could increase step counts in a diverse, multilingual sample of people with diabetes and depression symptoms. From January 2020 to June 2022, participants were recruited from 4 San Francisco, California-based public primary care clinics and through web-based platforms to participate in the 24-week randomized controlled trial. Eligibility criteria included English or Spanish language preference and a documented diagnosis of diabetes and elevated depression symptoms. The trial had 3 arms: a Control group receiving a weekly mood monitoring message, a Random messaging group receiving randomly selected feedback and motivational text messages daily, and an Adaptive messaging group receiving text messages selected by a reinforcement learning algorithm daily. Randomization was performed with a 1:1:1 allocation. The primary outcome, changes in daily step counts, was passively collected via a mobile app. The primary analysis assessed changes in daily step count using a linear mixed-effects model. An a priori subanalysis compared the primary step count outcome within recruitment samples. In total, 168 participants were analyzed, including those with 24% (40/168) Spanish language preference and 37.5% (63/168) from clinic-based recruitment. The results of the linear mixed-effects model indicated that participants in the Adaptive arm cumulatively gained an average of 3.6 steps each day (95% CI 2.45-4.78; P<.001) over the 24-week intervention (average of 608 total steps), whereas both the Control and Random arm participants had significantly decreased rates of change. Postintervention estimates suggest that participants in the Adaptive messaging arm showed a significant step count increase of 19% (606/3197; P<.001), in contrast to 1.6% (59/3698) and 3.9% (136/3480) step count increase in the Random and Control arms, respectively. Intervention effectiveness differences were observed between participants recruited from the San Francisco clinics and those recruited via web-based platforms, with the significant step count trend persisting across both samples for participants in the Adaptive group. Our study supports the use of reinforcement learning algorithms for personalizing text messaging interventions to increase physical activity in a diverse sample of people with diabetes and depression. It is the first to test this approach in a large, diverse, and multilingual sample. ClinicalTrials.gov NCT03490253; https://clinicaltrials.gov/study/NCT03490253. RR2-10.1136/bmjopen-2019-034723.

Universal Design Element Utilization and Mathematics Performance: Implications for Diverse Student Populations

This empirical research study investigates the relationship between the utilization of Universal Design (UD) elements and math performance among eighth graders. We analyzed 2017 National Assessment of Educational Progress process data using Poisson Generalized Linear Mixed-Effects Models to examine how the frequency of UD element usage varies across diverse student demographics. Our findings reveal a great divide: lower achievers, students with disabilities, those from lower socioeconomic backgrounds, English Language Learners, and African American students predominantly use text-to-speech, whereas high achievers more frequently employ digital pencils (which allow for manual writing or drawing on the screen) and elimination capacity (which enables students to dismiss incorrect multiple-choice answers). Linear Mixed-Effects Models show that higher levels of utilization of digital pencils and elimination capacity are correlated with improved math performance across various student subgroups. However, frequent changes in color themes, intended to enhance visual differentiation, were associated with lower performance, suggesting that these might serve as distractions rather than aids for some students. We discuss the implications of the findings in terms of the design of UD elements, as well as for equity, accessibility, and math education more broadly.

Critical Impact of Working Distance on OCT Imaging: Correction of Optical Distortion and Its Effects on Measuring Retinal Curvature.

To assess the impact of working distance (WD) on optical distortion in optical coherence tomography (OCT) imaging and to evaluate the effectiveness of optical distortion correction in achieving consistent retinal Bruch's membrane (BM) layer curvature, regardless of variations in WD. Ten subjects underwent OCT imaging with four serial macular volume scans, each employing distinct WD settings adjusted by balancing the sample and reference arm of the OCT interferometer (eye length settings changed). Either of two types of 30° standard objectives (SOs) was used. A ray tracing model was used to correct optical distortion, and BM layer curvature (represented as the second derivative of the curve) was measured. Linear mixed effects (LME) modeling was used to analyze factors associated with BM layer curvature, both before and after distortion correction. WD exhibited significant associations with axial length (β = -1.35, P < 0.001), SO type (P < 0.001), and eye length settings (P < 0.001). After optical distortion correction, the mean ± SD BM layer curvature significantly increased from 16.80 ± 10.08µm-1 to 49.31 ± 7.50µm-1 (P < 0.001). The LME model showed a significant positive association between BM layer curvature and WD (β = 1.94, P < 0.001). After distortion correction, the percentage change in BM layer curvature due to a 1-mm WD alteration decreased from 9.75% to 0.25%. Correcting optical distortion in OCT imaging significantly mitigates the influence of WD on BM layer curvature, enabling a more accurate analysis of posterior eye morphology, especially when variations in WD are unavoidable.

28-country global study on associations between cultural characteristics and Recovery College fidelity.

Recovery Colleges (RCs) are learning-based mental health recovery communities, located globally. However, evidence on RC effectiveness outside Western, educated, industrialised, rich, and democratic (WEIRD) countries is limited. This study aimed to evaluate associations between cultural characteristics and RC fidelity, to understand how culture impacts RC operation. Service managers from 169 RCs spanning 28 WEIRD and non-WEIRD countries assessed the fidelity using the RECOLLECT Fidelity Measure, developed based upon key RC operation components. Hofstede's cultural dimension scores were entered as predictors in linear mixed-effects regression models, controlling for GDP spent on healthcare and Gini coefficient. Higher Individualism and Indulgence, and lower Uncertainty Avoidance were associated with higher fidelity, while Long-Term Orientation was a borderline negative predictor. RC operations were predominantly aligned with WEIRD cultures, highlighting the need to incorporate non-WEIRD cultural perspectives to enhance RCs' global impact. Findings can inform the refinement and evaluation of mental health recovery interventions worldwide.

Unexpected anthropogenic emission decreases explain recent atmospheric mercury concentration declines.

Anthropogenic activities emit ~2,000 Mg y-1 of the toxic pollutant mercury (Hg) into the atmosphere, leading to long-range transport and deposition to remote ecosystems. Global anthropogenic emission inventories report increases in Northern Hemispheric (NH) Hg emissions during the last three decades, in contradiction with the observed decline in atmospheric Hg concentrations at NH measurement stations. Many factors can obscure the link between anthropogenic emissions and atmospheric Hg concentrations, including trends in the reemissions of previously released anthropogenic ("legacy") Hg, atmospheric sink variability, and spatial heterogeneity of monitoring data. Here, we assess the observed trends in gaseous elemental mercury (Hg0) in the NH and apply biogeochemical box modeling and chemical transport modeling to understand the trend drivers. Using linear mixed effects modeling of observational data from 51 stations, we find negative Hg0 trends in most NH regions, with an overall trend for 2005 to 2020 of -0.011 ± 0.006 ng m-3 y-1 (±2 SD). In contrast to existing emission inventories, our modeling analysis suggests that annual NH anthropogenic emissions must have declined by at least 140 Mg between the years 2005 and 2020 to be consistent with observed trends. Faster declines in 95th percentile Hg0 values than median values in Europe, North America, and East Asian measurement stations corroborate that the likely cause is a decline in nearby anthropogenic emissions rather than background legacy reemissions. Our results are relevant for evaluating the effectiveness of the Minamata Convention on Mercury, demonstrating that existing emission inventories are incompatible with the observed Hg0 declines.

Evaluation of ComBat harmonization for reducing across-tracer differences in regional amyloid PET analyses.

Introduction Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [18F]-florbetapir (FBP) and [11C]-Pittsburgh Compound-B (PiB). Methods One-hundred-thirteen head-to-head FBP-PiB scan pairs, scanned from the same subject within ninety days, were selected from the Open Access Series of Imaging Studies 3 (OASIS-3) dataset. The Centiloid scale, ComBat with no covariates, ComBat with biological covariates, and GAM-ComBat with biological covariates were used to harmonize both global and regional amyloid standardized uptake value ratios (SUVR). Variants of ComBat, including longitudinal ComBat and PEACE, were also tested. Intraclass correlation coefficient (ICC) and mean absolute error (MAE) were computed to measure the absolute agreement between tracers. Additionally, longitudinal amyloid SUVRs from an anti-amyloid drug trial were simulated using linear mixed effects modeling. Differences in rates-of-change between simulated treatment and placebo groups were tested, and change in statistical power/Type-I error after harmonization was quantified. Results In the head-to-head tracer comparison, ComBat with no covariates was the best at increasing ICC and decreasing MAE of both global summary and regional amyloid PET SUVRs between scan pairs of the same group of subjects. In the clinical trial simulation, harmonization with both Centiloid and ComBat increased statistical power of detecting true rate-of-change differences between groups and decreased false discovery rate in the absence of a treatment effect. The greatest benefit of harmonization was observed when groups exhibited differing FBP-to-PiB proportions. Conclusion ComBat outperformed the Centiloid scale in harmonizing both global and regional amyloid estimates. Additionally, ComBat improved the detection of rate-of-change differences between clinical trial groups. Our findings suggest that ComBat is a viable alternative to Centiloid for harmonizing regional amyloid PET analyses.

Somatic and mental symptoms associated with dysglycaemia, diabetes-related complications and mental conditions in people with diabetes: Assessments in daily life using continuous glucose monitoring and ecological momentary assessment.

To analyse the potential drivers (glucose level, complications, diabetes type, gender, age and mental health) of diabetes symptoms using continuous glucose monitoring (CGM) and ecological momentary assessment. Participants used a smartphone application to rate 25 diabetes symptoms in their daily lives over 8 days. These symptoms were grouped into four blocks so that each symptom was rated six times on 2 days (noon, afternoon and evening). The symptom ratings were associated with the glucose levels for the previous 2 hours, measured with CGM. Linear mixed-effects models were used, allowing for nested random effects and the conduct of N = 1 analysis of individual associations. In total, 192 individuals with type 1 diabetes and 179 with type 2 diabetes completed 6380 app check-ins. Four symptoms showed a significant negative association with glucose values, indicating higher ratings at lower glucose (speech difficulties, P = .003; coordination problems, P = .00005; confusion, P = .049; and food cravings, P = .0003). Four symptoms showed a significant positive association with glucose values, indicating higher scores at higher glucose (thirst, P = .0001; urination, P = .0003; taste disturbances, P = .021; and itching, P = .0120). There were also significant positive associations between microangiopathy and eight symptoms. Elevated depression and diabetes distress were associated with higher symptom scores. N = 1 analysis showed highly idiosyncratic associations between symptom reports and glucose levels. The N = 1 analysis facilitated the creation of personalized symptom profiles related to glucose levels with consideration of factors such as complications, gender, body mass index, depression and diabetes distress. This approach can enhance precision monitoring for diabetes symptoms in precision medicine.

Influence of Neuromuscular Activity and Technical Determinants on Scull Rowing Performance

Rowing is a complex sport where technique can significantly impact performance. A better understanding of the rowers’ technique and neuromuscular activations during scull rowing, along with their impact on rowing performance, could greatly help trainers and athletes. Twelve male rowers were asked to row at their competitive stroke rate, and we collected data describing neuromuscular activations, trunk and arm kinematics, as well as technical determinants such as oar angles and angle asymmetries. We fitted linear mixed-effect models to investigate the effects of these variables on power production and boat speed. A larger effective angle had the greatest positive effect on power output, and slip angles had the largest negative effects. Increased elbow flexion at catch had the greatest negative effect on speed. Angle asymmetries affected neither power nor speed. Increased upper limb neuromuscular activity during the first and third quarters of the drive phase helped reduce slip angles, thus increasing performance. Power and speed were influenced similarly by the predictor variables. Still, they showed subtle differences, indicating that the strategies to maximize power production might not be the best ones to also achieve the maximum speed.

Effect of a small increase in off-premises trading hours on alcohol sales in Norway: A stepped-wedge cluster-randomized controlled trial.

Evidence of the effect of limiting off-premises alcohol trading hours is still scarce. This study tested the effect of a small extension in trading hours on alcohol sales in alcohol monopoly outlets in Norway. The extension of trading hours was implemented within a stepped-wedge cluster-randomized trial design. Eligible state monopoly outlets (n = 229) were clustered into trade districts (n = 62), which were block-randomized to one of three sequences regarding date of implementation: 1 September 2020 (n = 21 districts, 82 outlets), 1 December 2020 (n = 21 districts, 73 outlets) and 1 March 2021 (n = 20 districts, 74 outlets). Outcomes were followed-up for a 1-year period. Study participants were state monopoly outlets in urban and rural trade districts in all parts of Norway. Monthly alcohol sales in litres of pure alcohol per trade district and per outlet were measured from March 2020 to March 2022 (primary outcome). We applied a linear mixed-effect model with two-way fixed effects within a difference-in-difference framework. As a robustness check we considered the effects of cross-border trade and effects in subgroups of outlets. Trading hours in monopoly outlets were extended by 1 hour on Saturdays. The extension was permanent. Pre-intervention periods and not-yet-treated units served as control conditions. We did not find a statistically significant effect of the small extension in trading hours on monthly alcohol sales (i) per trade district [average treatment effect: -185.5litres, 95% confidence interval (CI) = -1159.9, 788.9] and (ii) per outlet (-35.3litres, 95% CI = -142.1, 72.0). These findings were consistent across estimation methods and model specifications. There is no clear evidence that a small extension in off-premises trading hours affected alcohol sales in monopoly outlets in Norway.

Examining the effect of soil organic carbon on major Canadian Prairie crop yields with predictive soil mapping

AbstractMaintaining soil organic carbon (SOC) is critical for global food security as it is essential for soil functions that sustain crop yields. There has been an increase in predictive soil mapping, which when combined with extensive crop yield datasets, enables a better understanding of crop yield and SOC relationships. This study focused on updating maps of SOC content in Saskatchewan using recently digitized historical SOC datasets and predictive soil mapping, and using the maps to examine the relationship between SOC and crop yield. A database of 5014 SOC values was used to map SOC contents using a Random Forest model and a range of environmental covariates. The final SOC model had a R2 of 0.48, root mean square error of 0.98%, concordance correlation coefficient of 0.67, and a bias of 0.12%. The relationship between mapped SOC values and crop yield data, with 100,000–200,000 records depending on crop type, was then assessed using a linear mixed effects model after normalizing the data by rural municipality to remove broad‐scale climate effects. Overall, an increase in SOC by 1% led to an increase on average of 263 kg ha−1 for wheat (Triticum aestivum L.), 293 kg ha−1 for barley (Hordeum vulgare L.), 133 kg ha−1 for canola (Brassica napus L.), and 135 kg ha−1 for field peas (Pisum sativum L.). These results show that increasing SOC was associated with greater yields for four major crops in Saskatchewan, with the largest gains occurring when the initial SOC contents are lower.

Metalinguistic explanations and their impact on incidental grammar acquisition: An eye-movement study

Recent research highlights the value of metalinguistic explanations in facilitating second language (L2) grammar acquisition. Nevertheless, a notable research gap persists regarding how these explanations influence incidental grammar acquisition and their impact on overall reading processes and comprehension. Furthermore, whether the potentially positive effects of metalinguistic explanations transfer to the acquisition of subsequent constructions without explicit guidance is an unexplored domain. This study addresses these research gaps by recruiting 42 Korean undergraduate students and assigning them to the metalinguistic or baseline groups. The metalinguistic group read an English text supplemented with bottom-margin metalinguistic explanations, which elucidated the first half of the target grammar (without explanations for the second half), whereas the baseline group read the same text without explanations. This study used eye-tracking technology to register participants’ eye movements during reading, followed by an announced reading comprehension test and an unannounced error correction test. Statistical analyses using linear mixed-effects models (LMMs) and t-tests revealed that metalinguistic explanations significantly enhanced incidental grammar acquisition in L2 learners without compromising overall reading processes and comprehension. However, the benefits of metalinguistic explanations in the metalinguistic group failed to extend to the incidental learning of other unexplained constructions.

8413 Skeletal Muscle Mass, Insulin Sensitivity, And Beta-Cell Function In The Development Of Type 2 Diabetes: A 16-Year Prospective Cohort Study

Abstract Disclosure: H. Mun: None. S. Lee: None. S. Kim: None. S. Yoo: None. J. Son: None. Background: The relationship of relative muscle mass with beta-cell dysfunction and insulin resistance in the development of type 2 diabetes is unclear. We therefore aimed to evaluate longitudinal changes in glycemia, insulin sensitivity, and beta-cell function according to muscle mass. Methods: We prospectively evaluated 7090 middle-aged and older participants without diabetes at baseline every 2 years with oral glucose tolerance tests for 16 years in the Korean Genome Epidemiology Study. Weight-adjusted appendicular skeletal muscle mass was used to derive the muscle mass index (MMI). Using linear mixed-effect models, we assessed trajectories of fasting and 2-hour post-load glucose (2hPG), the composite insulin sensitivity index (ISIcomp), the 60-minute insulinogenic index (IGI60), and the disposition index (DI) according to sex-specific MMI tertiles before diagnosis with type 2 diabetes or the completion of follow-up. Results: During a median follow-up of 13.9 years, 1742 (24.5%) participants were diagnosed with type 2 diabetes. The risk of developing type 2 diabetes gradually increased as MMI decreased (multivariable-adjusted hazard ratio 1.36; 95% CI 1.29; 1.44 per SD decline in MMI). After age- and sex adjustment, significant differences were found in fasting and 2hPG trajectories between low and high MMI tertiles during follow-up (p &amp;lt; 0.001 for group-by-time interaction). The low MMI tertile showed significantly lower ISIcomp and DI at baseline compared to the high MMI tertile. The rate of increase in IGI60 was significantly lower in the low MMI tertile than in the high MMI tertile (0.0021 vs. 0.0191; p &amp;lt; 0.001) despite a progressive decline in ISIcomp during follow-up. The rate of decrease in DI was significantly greater in the low MMI tertile than in the high MMI tertile (-0.0228 vs. -0.006; p &amp;lt; 0.001). Conclusion: Sufficient muscle mass in middle-aged and older adults could protect against incident type 2 diabetes by preserving beta-cell function to compensate for aging-induced reductions in insulin action, independent of obesity. Presentation: 6/1/2024

Anthropogenic double jeopardy: Urban noise and artificial light at night interact synergistically to influence abundance

Artificial light at night (ALAN) and urban noise are increasing globally and can have a range of impacts on wildlife. While ALAN and noise often co-occur and can affect wildlife in similar ways, their impacts have generally been studied in isolation. Information about possible interactive impacts, which can be more serious, is critical to guide conservation.We studied how noise and ALAN impact a common urban waterbird (Eurasian coot Fulica atra) around the city of Melbourne in south-eastern Australia. We aimed to examine: (1) the individual and (2) interactive impacts of noise and ALAN on abundance, and (3) the relative influence of these stressors and other environmental predictors. To do so, we used data from a large-scale (1,463 surveys across an area of 9,250 km2 with significant heterogeneity in noise and ALAN conditions), long-term (2008–2018) monitoring program, overlaid with georeferenced noise and light data. We used generalized linear mixed effects models and boosted regression trees to model individual and interactive effects of ALAN and noise on abundance.Abundance was negatively correlated with noise and ALAN individually. Furthermore, the two stressors had a negative synergistic effect, ultimately resulting in the absence of coots at the highest observed ALAN and noise levels. We also estimate that the combined influence of the two stressors on abundance was larger than that of other examined environmental factors.Our findings that noise and ALAN have detrimental interactive impacts is worrying for two reasons. First, Eurasian coots are thought to be tolerant to urbanisation, so impacts may be more severe for less tolerant species. Second, noise and ALAN commonly co-occur around cities, so similar impacts are likely elsewhere. By adopting more biologically and ecologically realistic analytical frameworks, future studies can better estimate the cumulative impacts of multiple stressors to facilitate improved conservation and management.

8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study

Abstract Disclosure: A.O. Agbaje: None. Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p&amp;lt;0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p&amp;lt;0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p&amp;lt;0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p&amp;lt;0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood. Presentation: 6/1/2024

7310 System-level Analysis in Polycystic Ovary Syndrome on a Panel of Genetically Diverse Strains of Mice

Abstract Disclosure: L.M. Velez: None. C. Johnson: None. I. Tamburrini: None. M. Zhou: None. C. Viesi: None. N. Ujagar: None. D. Ashbrook: None. M. Nelson: None. A. Senior: None. D. James: None. R. Williams: None. D. Nicholas: None. M. Seldin: None. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, with a prevalence of ∼4-20% in women of reproductive age. The diagnosis of the syndrome generally occurs when the patient consults for fertility issues and is only based on a reproductive criterion, which includes (1) hyperandrogenism, (2) oligo-anovulation, and (3) polycystic ovary morphology. However, the overlap of PCOS with cardiometabolic diseases is significant. To put in numbers; up to 75% of PCOS women present some degree of insulin insensitivity, 38-88% present obesity or overweight, 20-50% develop type 2 diabetes by age 40, and PCOS women are at increased risk of cardiovascular disease. Despite these facts, shared reproductive/metabolic mechanisms are largely underexplored. Moreover, studies addressing the genetic architecture of PCOS are missing. Here, we induced a PCOS-like condition in 25 recombinant and classical inbred female strains and matched placebo controls over 6 weeks. Comprehensive in vivo and terminal reproductive/metabolic analyses were performed, as well as ovary and adipose RNA-Seq. These strains varied in PCOS response in a number of key metabolic and reproductive traits, including circulating hormone levels, glucose metabolism, and cardiac function. We applied a linear mixed-effects model to estimate heritability, and genetic (h2), PCOS, and gene-by-PCOS interactions. High h2 was observed for lean and fat mass, glucose, and AUC, whereas PCOS effects were high for the BW change, testosterone, and AUC. Substantial gene-by-PCOS interactions were found for reproductive hormones. Undirected network construction and centrality estimates showed that the reproductive hormones LH and LH/FSH ratio were the strongest central traits connecting metabolic phenotypes. We also showed select strains represent subtypes of human PCOS-metabolism interaction with varied susceptibilities to disease in a PCOS setting. Ovarian RNA-seq analysis of PCOS DEGs showed strong enrichments with human disease settings such as hyperandrogenism, inflammation, and pregnancy hypertension. Similar analyses in GWAT RNA-seq showed enrichments in weight gain, liposarcoma, inflammation, and reproductive diseases were at the top, with adipose genes connecting these diseases and potentially involved with PCOS. In conclusion, we established a PCOS model to study relevant mechanisms intersecting reproduction with metabolism in the context of genetic variation. Presentation: 6/2/2024