Linear Effects Models Research Articles

Establishment of an Integrated Population Pharmacokinetic/Pharmacodynamics Model of Apixaban in Chinese Healthy Population Adjusting for Key Genetic Variants.

To improve the understanding of pharmacokinetic/pharmacodynamic (PK/PD) profiles of apixaban, supporting personalised drug prescriptions for future patients. Genetic as well as nongenetic factors can affect the predictable PK and PD characteristics of apixaban. Establish a integrated popPK/PD model that adjusts for critical genetic variant. The integrated PK/PD models was characterized on the basis of PK (apixaban blood concentration) and PD (prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-FXa activity) data from 181 healthy Chinese volunteers. Other investigated covariate variables included: Meaningful intrinsic and extraneous determinants, correlated markers (ABCG2, F13A1, C3, etc.). A total of 2877 PK concentration observations were included in the modeling dataset. The PK model of apixaban is adopted by single compartment model with first-order oral absorption. The estimated values of total clearance rate (CL/F), apparent distribution volume (V/F), and absorption rate constant (KA) in the final model are 3.37 l/h, 28.2 l, and 0.781 l/h, respectively. The PK model includes significance covariates such as FOOD, RBC, WT, and gene (ABCG2). The PD model of apixaban is adopted by a linear direct effect model with additive error, which was used to describe the relationship between markers such as APTT, PT, anti-FXa, versus plasma concentration. PK simulation within the modelled dose range is similar to clinical real date, while PD simulation results also show that the simulated exposure parameters is within the range of the literature. We established a comprehensive PK/PD model and used it to simulate markers level such as APTT, PT, and anti-FXa of apixaban. Individual predictive values with a dose of 2.5 mg are basically within the expected recommended range.

Associations between blood nickel and lung function in young Chinese: An observational study combining epidemiology and metabolomics

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

Prefrontal cortex activation under stress as a function of borderline personality disorder in female adolescents engaging in non-suicidal self-injury.

Neuroimaging studies suggest alterations in prefrontal cortex (PFC) activity in healthy adults under stress. Adolescents with non-suicidal self-injury (NSSI) report difficulties in stress and emotion regulation, which may be dependent on their level of borderline personality disorder (BPD). The aim was to examine alterations in the PFC in adolescents with NSSI during stress. Adolescents (13-17 years) engaging in non-suicidal self-injury (n = 30) and matched healthy controls (n = 29) performed a task with low cognitive demand and the Trier Social Stress Test (TSST). Mean PFC oxygenation across the PFC was measured with an eight-channel near-infrared spectroscopy system. Alongside self-reports on affect, dissociation and stress, BPD pathology was assessed via clinical interviews. Mixed linear-effect models revealed a significant effect of time on PFC oxygenation and a significant time×group interaction, indicating increased PFC activity in patients engaging in NSSI at the beginning of the TSST compared with healthy controls. Greater BPD symptoms overall were associated with an increase in PFC oxygenation during stress. In exploratory analyses, mixed models addressing changes in PFC connectivity over time as a function of BPD symptoms were significant only for the left PFC. Results indicate differences in the neural stress response in adolescents with NSSI in line with classic neuroimaging findings in adults with BPD. The link between PFC oxygenation and measures of BPD symptoms emphasises the need to further investigate adolescent risk-taking and self-harm across the spectrum of BPD, and maybe overall personality pathology, and could aid in the development of tailored therapeutic interventions.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Dissecting heritability, environmental risk, and air pollution causal effects using > 50 million individuals in MarketScan

Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM2.5), nitrogen dioxide (NO2), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM2.5 or NO2 have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM2.5 and NO2 tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.

Desensitizing efficacy of a universal dentin adhesive containing mesoporous bioactive glass on dentin hypersensitivity: a randomized clinical trial with a split-mouth model

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.

Predictors of improvement in LV ejection fraction post PVC ablation

Abstract Introduction Premature ventricular contraction (PVC) is a frequently encountered finding in routine ECGs, that in certain individuals may be followed by reduction in ejection fraction (EF). This may be improved or even reversed with a medical or interventional reduction of ectopic burden. Objective The primary objective of this study is to assess the potential effectiveness of cardiac ablation in suppressing PVC and subsequently enhancing the EF. Further we aim to establish predictive factors of the success of the intervention. Methods In a retrospective data analysis at a single medical centre, we examined records of 116 patients who underwent ectopic ablation, with 10 patients having more than 1 ablation. Demographic information, heart-related conditions along with the presence of a scar on MRI, was collected. The study also recorded pre- and post-procedure PVC burden and EF measurements. Results Demographics and procedural details are in table 1. It was found that patients participating in this study were predominantly male (66.4%), on average 60.1 (± 13.6) years old, overweight (BMI 29.8 ± 5.4) with no additional heart disease (56%) and no scarring on MRI (55%).The PVC burden before ablation (27.9 ± 12.7) significantly reduced to 8.0 ± 11.2 post-ablation (p &amp;lt; 0.005), marking an average relative reduction of 68.1% (± 44.1%). Successful interventions, defined by a reduction exceeding 50%, were observed in 79% of patients. The EF increased from 39.6 ± 8.9 to 47.5 ± 10.7 post-ablation (p &amp;lt; 0.005), corresponding to an average increase by 8.4 ± 8.5. Notably amongst the patients who had a successful ablation, 36% of patients achieved normalized EF (&amp;gt;55%) and 42% showed an improvement of at least 5%. A strong correlation emerged between the relative change in PVC and the ejection fraction measured after ablation, with an increase by 0.10 for every percent reduction (p &amp;lt; 0.00). The relative increase in the EF% was significantly higher in patients where the PVC burden was reduced by at least 50% (figure 1). Linear fixed effect modelling explored the influence of patient characteristics on the model. Patients with higher BMI had a lower EF after ablation with same relative reduction in PVC (p &amp;lt; 0.03). Similarly, a scar on MRI and associated heart condition was associated with reduced improvement in ejection fraction (p &amp;lt; 0.02). Also, for every increase in age patients had a reduction of 0.2 EF after ablation (p &amp;lt; 0.01). Right heart PVC’s were ablated more successfully, and had higher EF post ablation (p &amp;lt; 0.01). Conclusion In conclusion, reduction in PVC burden increases the EF after treatment. Increasing BMI, age and presence of associated heart disease can negatively impacted LVEF post ablation. Further research could improve the model that predicts improvement in LV function post successful PVC ablation.Figure 1Table 1

Incidence of diabetes and influencing factors in HIV-infected individuals after antiretroviral therapy in Dehong Dai and Jingpo Autonomous Prefecture

Objective: To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong). Methods: The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4. Results: A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions: The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

Head Exposure to Acceleration Database in Sport (HEADSport): a kinematic signal processing method to enable instrumented mouthguard (iMG) field-based inter-study comparisons

ObjectiveInstrumented mouthguard (iMG) systems use different signal processing approaches limiting field-based inter-study comparisons, especially when artefacts are present in the signal. The objective of this study was to assess the...

Effects on local oxygen conditions by the invasive macrophyte Myriophyllum spicatum

Myriophyllum spicatum, Eurasian watermilfoil, is a submerged aquatic plant invasive to North America. Several characteristics found in M. spicatum provide reasoning behind its invasion success such as its ability to spread and grow rapidly as well as displace other surrounding native species. However, Eurasian watermilfoil’s effects on ecosystem functioning (such as dissolved oxygen) and how such functioning differ from effects of native vegetation have seldom been studied. Using data collected in field, we used statistical models including Gaussian multivariate linear effect models and structural equation modelling (SEM), to investigate the effect of vegetation type and cover on dissolved oxygen (DO) and temperature gradients. Here, we show that invasive Eurasian watermilfoil colonies, relative to native submerged vegetation, can have a direct effect on DO gradients. These changes in DO conditions were driven by both an increase in surface oxygen concentrations and a decrease in bottom layer oxygen concentration in dense M. spicatum vegetation. Furthermore, we find that the differences in DO gradients could be predicted from M. spicatum’s direct impact on oxygen concentration and not indirectly via its effects on water temperature. Our results demonstrate that dense colonies of M. spicatum can directly affect DO concentrations and may do so more than native macrophytes which could explain its rapid spread and potential impacts on ecosystem functioning.

Change in life space is associated with cognitive decline and increased risk of incident Alzheimer’s and Parkinson’s disease in older men

AbstractBackgroundLife space measures the range of geospatial movement through one’s environment during daily functioning. Prior studies on the association of life space and cognitive change are mostly cross‐sectional and have mixed results. To clarify this association, we prospectively evaluated change in life space with cognitive decline and incident Alzheimer’s disease (AD) and Parkinson’s disease (PD).MethodWe studied 1,684 men enrolled in a prospective study of aging. We excluded individuals with probable dementia or PD at baseline (Study Year 7). Life space was evaluated with the self‐reported University of Alabama at Birmingham Life Space Assessment at Year 7 and Year 14. The composite life space score ranges from 0 (most restricted) to 120 (least restricted). Incident AD or PD was defined as a self‐reported physician diagnosis or medication use at Year 14. We conducted logistic regression analyses examining change in life space with the odds of our outcomes unadjusted and adjusted for age, clinic site, race, education, living arrangement, vascular risk factors, and depression. We also conducted mixed linear effects models to evaluate the association between change in life space and change in 3MS and Trails B score.ResultOf 1,684 men (mean age 77.1 +/‐ 18.7 SD) in our analytic cohort, 80 (4.8%) developed incident AD and 23 (1.4%) developed PD over 7 years. The mean (SD) life space score at baseline was 92.9 (18.7) and change over 7 years was ‐9.9 (22.3). In the fully adjusted model, each 1 SD decrement in life space was associated with increased odds of AD (OR 1.6, 95% CI 1.3, 2.0) and PD (OR 1.6, 95% CI 1.1, 2.5). For each 1 SD decline in life space, men worsened by 20.6 seconds in their Trails B score and 1.15 points in their 3MS score over 7 years (p&lt;0.001 for both).ConclusionIn this novel longitudinal analysis, decline in life space is associated with cognitive decline and incident AD and PD. Future studies should examine whether decline in life space is a sensitive and practical way to identify older individuals at risk for cognitive dysfunction and neurodegenerative disease.

Abstract C020: Racial differences in distress levels among Black and White hormone receptor–positive breast cancer survivors over a 3-year period

Abstract Purpose: The purpose of this study was to determine longitudinal racial variations in distress levels among Black and White women with hormone receptor-positive (HR+) breast cancer. Methods: This is a secondary data analysis from the Women’s Hormonal Initiation and Persistence (WHIP) Study, an observational study of HR+ breast cancer survivors. Data regarding patient demographics (e.g., race, age, education, income) were collected via surveys. Clinicopathologic factors (e.g., stage, type of surgery, chemotherapy, and radiation) and medication type (tamoxifen vs. aromatase inhibitors) were extracted from medical records. The National Comprehensive Cancer Network’s Distress Thermometer was used to capture distress following AET initiation at 4 timepoints (baseline, year 1, year 2 and year 3). Mixed linear effects models were used to identify differences in distress by race over the 3-year period. An unadjusted model included race and time as covariates, whereas the adjusted model controlled for demographics, clinicopathologic factors and medication type. Results: The total sample was comprised of 572 women (410 White and 162 Black). For the unadjusted model, the race by time interaction was not statistically significant (F3, 1002.53= 2.2895, p = 0.077). However, the race by time interaction was statistically significant in the adjusted model (F3, 670.99 = 2.68, p = 0.04576), such that Black survivors experienced increased distress over time compared to White survivors. Age was the only statistically significant covariate as older women had lower distress compared to their younger counterparts (p= 0.01) Conclusion. Black and White HR+ breast cancer survivors had different distress levels over a 3-year period. Over time Black survivors’ distress remained high compared to their White counterparts. It is important to consider these differences, given that Black women have higher breast cancer related morbidity and mortality. Future work should focus on the development of culturally appropriate interventions for distress management in HR+ Black breast cancer survivors. Citation Format: Fariha Tariq, Teletia Taylor, Robert A. Perera, Vanessa B. Sheppard. Racial differences in distress levels among Black and White hormone receptor–positive breast cancer survivors over a 3-year period [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C020.

Assessing the Impacts of Lead Corrosion Control on the Microbial Ecology and Abundance of Drinking-Water-Associated Pathogens in a Full-Scale Drinking Water Distribution System.

Increases in phosphate availability in drinking water distribution systems (DWDSs) from the use of phosphate-based corrosion control strategies may result in nutrient and microbial community composition shifts in the DWDS. This study assessed the year-long impacts of full-scale DWDS orthophosphate addition on both the microbial ecology and density of drinking-water-associated pathogens that infect the immunocompromised (DWPIs). Using 16S rRNA gene amplicon sequencing and droplet digital PCR, drinking water microbial community composition and DWPI density were examined. Microbial community composition analysis suggested significant compositional changes after the orthophosphate addition. Significant increases in total bacterial density were observed after orthophosphate addition, likely driven by a 2 log 10 increase in nontuberculous mycobacteria (NTM). Linear effect models confirmed the importance of phosphate addition with phosphorus concentration explaining 17% and 12% of the variance in NTM and L. pneumophila density, respectively. To elucidate the impact of phosphate on NTM aggregation, a comparison of planktonic and aggregate fractions of NTM cultures grown at varying phosphate concentrations was conducted. Aggregation assay results suggested that higher phosphate concentrations cause more disaggregation, and the interaction between phosphate and NTM is species specific. This work reveals new insight into the consequences of orthophosphate application on the DWDS microbiome and highlights the importance of proactively monitoring the DWDS for DWPIs.

Constricting Life Space and Likelihood of Neurodegenerative Disease in Community-Dwelling Older Men

Life space is a measure of the frequency, range, and independence of movement through the environment. There is increasing interest in life space as a holistic measure of function in older adults, but the association between change in life space and incident neurodegenerative disease is unknown. To evaluate the association between change in life space and cognitive decline or incident neurodegenerative disease over 7 years among community-dwelling older men. In this cohort study, logistic regression analyses were used to examine the association of baseline and change in life space with change in cognition unadjusted and adjusted for demographics, cardiovascular risk factors, depression, gait speed, and physical activity. Mixed linear effects models were used to evaluate the association between change in life space and change in cognition. Men were recruited from 6 US sites to participate in a prospective, community-based cohort study of aging and followed-up from 2007 to 2014. Individuals with prevalent dementia or Parkinson disease (PD) at baseline were excluded. Data were analyzed from May 2022 to September 2023. Life space, assessed using the University of Alabama at Birmingham Life Space Assessment and divided into tertiles. Participants completed the Modified Mini-Mental State (3MS) Test, and Trail-Making Test Part B at baseline and 7 years later. At follow-up, participants were asked about a new physician diagnosis of dementia and PD. A total of 1684 men (mean [SD] age, 77.1 [4.2] years) were recruited and over 7 years of follow-up, 80 men (4.8%) developed dementia and 23 men (1.4%) developed PD. Mean (SD) life space score was 92.9 (18.7) points and mean (SD) change was -9.9 (22.3) points over follow up. In the adjusted model, each 1-SD decrement in life space was associated with increased odds of dementia (odds ratio [OR], 1.59; 95% CI, 1.28-1.98) but not PD (OR, 1.48; 95% CI, 0.97-2.25). For each 1-SD decrement in life space, men worsened by 20.6 (95% CI, 19.8-21.1) seconds in their Trails B score (P < .001) and declined by 1.2 (95% CI, 1.0-1.3) points in their 3MS score (P < .001) over 7 years. In this study of 1684 men followed up over 7 years, change in life space was associated with faster cognitive decline and increased likelihood of neurodegenerative illness. Future studies should examine the role of clinician assessments or wearable electronics in tracking life space in older adults at risk of cognitive decline and neurodegenerative illness.

Carbon Emission Performance of Robot Application: Influencing Mechanisms and Heterogeneity Characteristics

With the new round of technological revolution and industrial change, industrial robots have an important role to play in the fight against climate change and in achieving the goal of “carbon peaking and carbon neutrality.” Based on the panel data of the application level of industrial robots in Shanghai and Shenzhen A-share listed companies from 2011 to 2019, this study examines the impact of industrial robots on carbon emission performance and discusses specific ways industrial robots can affect carbon emission performance. The results show that industrial robots can significantly improve carbon emission performance. Mechanism analysis shows that industrial robots can improve carbon emission performance through productivity and competition effects. Heterogeneity analysis shows that the application effect of industrial robots varies based on enterprise nature, regional location, and carbon emission intensity. The study can make potential contributions. First, this study systematically analyzes the impact of artificial intelligence technology on carbon emissions from the perspective of carbon emission performance, which can supplement the research on carbon emission performance. Second, this study calculates application levels of artificial intelligence technology at the enterprise level and uses panel and linear intermediary effect models to analyze the transmission mechanism between the application of artificial intelligence technology and carbon emission performance. Third, the heterogeneity analysis results can provide empirical support for formulating differentiated artificial intelligence carbon reduction strategies and be used as a reference to further promote the green development of artificial intelligence technology.

P029 Comparing the Impact of General Strength Conditioning and Motor Control Manual Therapy on Sleep Quality in Adults with Chronic Low Back Pain: A Randomised Controlled Trial

Abstract Introduction There is strong evidence indicating interactions between sleep and chronic low back pain (CLBP). However, evidence on the effect of exercise training (first-line treatment for CLBP), especially of specific modes of exercise training, on sleep is limited. This study aimed to investigate the effect of two exercise-based interventions (general strength and conditioning [GSC] and motor control and manual therapy [MCMT]) on sleep quality in adults with CLBP. Methods We conducted a two-group parallel (1:1), randomised controlled trial. Forty adults (mean age [SD]: 34.7 [6.1] years) with CLBP were randomised to receive either GSC (n=20) or MCMT (n=20) for 6 months. Sleep quality and its sub-components (e.g., sleep disturbance, sleep duration) were measured by the Pittsburgh Sleep Quality Index (PSQI). Analysis employed an intention-to-treat approach and group-by-time effects were assessed with mixed linear effect models. Results Both GSC (PSQI mean change [95%CI]: -1.58 [-2.70, -0.46] points) and MCMT (-1.61 [ 2.79, -0.43]) improved sleep quality at 6 months, but no group-by-time effect was detected (β [95%CI]: 0.03 [-1.60, 1.65]). For sleep quality sub-components, GSC improved daytime dysfunction (-0.33 [-0.65, -.0.01]), but led to a small decline in sleep efficiency (0.06 [0.01, 0.10]). MCMT improved sleep disturbance ( 0.31 [-0.55, -0.07]). Conclusion Both GSC and MCMT improved sleep quality, although neither intervention appeared superior. Sleep disturbance was improved in the MCMT group and daytime dysfunction was improved in the GSC group. Future studies would benefit from including a true control, objective sleep measures, and investigation of potential mediators.

Diffuse traumatic brain injury substantially alters plasma growth hormone in the juvenile rat.

Traumatic brain injury (TBI) can damage the hypothalamus and cause improper activation of the growth hormone (GH) axis, leading to growth hormone deficiency (GHD). GHD is one of the most prevalent endocrinopathies following TBI in adults; however, the extent to which GHD affects juveniles remains understudied. We used postnatal day 17 rats (n = 83), which model the late infantile/toddler period, and assessed body weights, GH levels, and number of hypothalamic somatostatin neurons at acute (1, 7 days post injury (DPI)) and chronic (18, 25, 43 DPI) time points. We hypothesized that diffuse TBI would alter circulating GH levels because of damage to the hypothalamus, specifically somatostatin neurons. Data were analyzed with generalized linear and mixed effects models with fixed effects interactions between the injury and time. Despite similar growth rates over time with age, TBI rats weighed less than shams at 18 DPI (postnatal day 35; P = 0.03, standardized effect size [d] = 1.24), which is around the onset of puberty. Compared to shams, GH levels were lower in the TBI group during the acute period (P = 0.196; d = 12.3) but higher in the TBI group during the chronic period (P = 0.10; d = 52.1). Although not statistically significant, TBI-induced differences in GH had large standardized effect sizes, indicating biological significance. The mean number of hypothalamic somatostatin neurons (an inhibitor of GH) positively predicted GH levels in the hypothalamus but did not predict GH levels in the somatosensory cortex. Understanding TBI-induced alterations in the GH axis may identify therapeutic targets to improve the quality of life of pediatric survivors of TBI.

Linear panel regressions with two-way unobserved heterogeneity

We study linear panel regression models in which the unobserved error term is an unknown smooth function of two-way unobserved fixed effects. In standard additive or interactive fixed effect models the individual specific and time specific effects are assumed to enter with a known functional form (additive or multiplicative). In this paper, we allow for this functional form to be more general and unknown. We discuss two different estimation approaches that allow consistent estimation of the regression parameters in this setting as the number of individuals and the number of time periods grow to infinity. The first approach uses the interactive fixed effect estimator in Bai (2009), which is still applicable here, as long as the number of factors in the estimation grows asymptotically. The second approach first discretizes the two-way unobserved heterogeneity (similar to what Bonhomme et al., 2021 are doing for one-way heterogeneity) and then estimates a simple linear fixed effect model with additive two-way grouped fixed effects. For both estimation methods we obtain asymptotic convergence results, perform Monte Carlo simulations, and employ the estimators in an empirical application to UK house price data.

Comparing self-harming intentions underlying eating disordered behaviors and nonsuicidal self-injury: Replication and extension in adolescents.

Eating disorder (ED) behaviors are often characterized as indirect forms of self-harm. However, recent research has found less clear demarcations between direct self-harming behaviors (e.g., nonsuicidal self-injury [NSSI], suicidal behaviors) than previously assumed. The aim of this study was to replicate findings of this prior research on adult populations in adolescents with a history of restrictive eating. A total of 117 adolescents between ages 12-14 were included in the study. Participants reported the presence and frequency of binge eating, compensatory, restrictive eating, and NSSI. Participants also reported thoughts of and intentions to hurt and kill themselves when engaging in each behavior on average. The t-tests and linear effects models were conducted to compare self-harming thoughts and intentions across behaviors. Participants reported at least some intent to hurt themselves physically in the moment and in the long-term when engaging in all ED behaviors and NSSI, and reported engaging in these behaviors while thinking about suicide. Direct self-harming knowledge and intentions were most frequently reported with NSSI and longer-term knowledge and intentions via NSSI and restrictive eating. Additionally, participants reported some suicidal thoughts and intentions across behaviors. This study replicates prior research, suggesting that adolescents engage in ED behaviors and NSSI with non-zero self-harming and suicidal thoughts and intentions. ED behaviors and NSSI may better be explained on a continuum. Implications include the recommendation of safety planning during ED treatment. This study highlights the overlap between eating disorder (ED) behaviors, nonsuicidal self-injury (NSSI), and suicide. Though clear distinctions typically exist for motives of self-harming behavior between ED behaviors (i.e., indirect, in the long run) and NSSI (i.e., direct, in the moment), this research suggests that intentions for self-harming and suicide may exist on a continuum. Clinical ED treatment should consider safety planning as part of routine interventions.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV. The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the nonrenal flare and long-term remission groups. Data from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (P< 0.001) but remained stable during a nonrenal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (P< 0.001), with a cutoff of 12.53 ng/mg urine creatinine yielding a sensitivity of 76.2% and a specificity of 68.4%. Urine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intrarenal complement activation and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.