Mixed Effects Research Articles

Right ventricular dysfunction parameters at echocardiography in patients with acute pulmonary embolism: meta-analysis of individual participant data

Abstract Background & Aim Echocardiography has a crucial role for decision making on management of patient with acute pulmonary embolism (PE) according to current international guidelines. However, the definition of right ventricle dysfunction (RVD) at echocardiography requires standardization. We performed an Individual patient data meta-analysis (IPDMA) to assess the role of individual parameters of RVD and of combinations of parameters for the prediction of short-term all-cause mortality and PE-related death. Methods A systematic search was run to identify clinical studies reporting on RVD at echocardiography and on short-term clinical outcome in patients with acute PE. Individual patient data from the original studies were pooled to perform a meta-analysis (IPDMA). The study outcomes were short-term death defined as death occurring within 30 days from PE diagnosis and PE-related death. Multiple imputation was used for the management of missing data. The odds ratio for all cause and PE related mortality were calculated using generalized linear mixed effects model. Results Individual data from 9,233 patients with acute PE from 16 studies were pooled in a unique database. All cause short-term mortality occurred in 9% of patients (95% CI 0.06-0.13, I2 93%). The IPDMA was feasible for the following parameters: tricuspid anulus systolic excursion (TAPSE), estimated pulmonary artery pressure (PAP) >30mmHg, right to left ventricle diameter ratio (RV/LV)>1, hypokinesia, paradoxical septal motion, RV diameter>30 mm and McConnel sign. All these parameters, except for PAP>30mmHg and RV diameter>30 mm, were predictors of short-term all cause death in the overall population and in hemodynamically patients (table). All the assessed RV findings, except for the McConnell’s sign, were predictors of PE-related death (Table). The presence of one RVD parameter only was not associated with increased risk of all cause death (OR 1.22, 95% CI 0.97-1-54), while the presence of two parameters or ≥ three parameters were (OR 1.63, 95% CI 1.24-2.15; OR 2.07 95% CI 1.59-2.69, respectively). Conclusion In patients with acute PE, the majority of RVD parameter at echocardiography are predictors of short-term death and of PE-related death. The higher the number of RVD parameters the worst the prognosis. These results claim for standardization in RVD definition to guide decision making for patient management.

Family-based sexual health intervention for adolescents; A systematic review and meta-analysis

Abstract Background Family-based interventions are important in promoting adolescent sexual health outcomes. However, the effectiveness of these interventions in promoting adolescent sexual and reproductive health (ASRH) in Lower and middle-income countries (LMIC) has not been empirically evaluated. This review aimed to summarise the effectiveness of family-based sexual and reproductive health interventions in promoting ASRH in LMIC. Methods We conducted a systematic search for studies published in English from 2000 to October 2023 using MEDLINE, PsyINFO, CINAHL, Web of Science, and EMBASE databases. Studies were included if they involved adolescents aged 10-19 years, included family members in a key intervention component, evaluated the effectiveness of the interventions using an experimental or quasi-experimental design, assessed ASRH outcomes reported by adolescents and were conducted in LMIC setting. Standardized mean difference (SMD) and 95% confidence intervals were computed and meta-analyses were conducted using random effect models. Results Ten articles involving 2,246 participants were included in the review. The studies were nostly conducted in Africa. Across studies, there was no significant impact of family-based interventions in improving adolescent sexual health knowledge (SMD=0.5, 95%CI: -1.98 to 2.98), attitudes (SMD= -0.05, 95%CI: -1.92 to 1.82), practices (SMD=0.53, 95%CI: -0.69 to 1.75), or sexual communication with their family (SMD= 0.14, 95%CI: -0.42 to 0.7). Although individual studies reported a mixed effect of family-based interventions in improving sexual health outcomes, the pooled results from the meta-analysis showed no significant impact of family-based interventions. Conclusions Our review did not find any significant impact of family-based interventions in improving ASRH in LMIC. We recommend interventions using innovative approaches and novel strategies to align with the socio-cultural and economic background of the study setting. Key messages • This study found no significant impact of family-based interventions in improving ASRH in LMIC. • Additional studies, particularly from Asia, using culturally relevant interventions is required in this area.

Risk factors for cardiometabolic multimorbidity: an analysis of 4 million participants from May Measurement Month 2017-2019

Abstract Background Cardiometabolic multimorbidity (CMM), defined as the presence of two or more cardiometabolic conditions, presents a significant global challenge due to aging populations and a growing prevalence of cardiometabolic diseases. However, evidence regarding the risk factors for CMM is scarce, particularly in low- and middle-income countries. May Measurement Month (MMM) is the largest annual global campaign collecting data on blood pressure (BP) and cardiometabolic diseases. Purpose To determine the proportion of hypertension in people with CMM and risk factors associated with CMM, from the three MMM campaigns in 2017-2019. Methods A total of 3 397 746 participants (≥18 years) were included, arising from 103 countries. CMM was defined as having two or more of three cardiometabolic diseases: myocardial infarction, stroke, and diabetes. Hypertension was defined as a systolic BP≥140mmHg and/or diastolic BP≥90mmHg, using the average of the second and third of three readings and/or taking antihypertensive medication. A multivariable logistic mixed effects regression model was used to examine associations between CMM and potential risk factors, including age, sex, BMI category, smoking status, and alcohol consumption in the model, with random effects for country. Results Amongst all participants, 316 940 (9.3%), 62 731 (1.8%), and 28 491 (0.8%) had one, two or three cardiometabolic conditions, respectively, and 91 222 (2.7%) had CMM. The proportion with hypertension increased with an increasing number of cardiometabolic conditions: 29.6% in those with none, and 63.0%, 68.6% and 71.2% in those with one, two, or three conditions, respectively. In a fully adjusted model, females had 16% (OR = 1.16, 95% CI: 1.12-1.20, p-value <0.001) higher odds of having CMM than males (Figure). Increasing age was associated with higher odds of having CMM, the highest risk being found in participants ≥70 years. Participants who were underweight, overweight, or obese, were more likely to have CMM than those with a healthy weight. Of the risk factors studied, current smoking was associated with the highest odds for CMM, (OR = 12.8, 95% CI: 12.62-13.04, p-value<0.001) compared with not smoking. Participants consuming alcohol at least once per week had 74% lower odds (OR = 0.26, 95% CI: 0.25-0.27, p-value <0.001) of having CMM compared with those who never or rarely consumed alcohol (Figure 1). Conclusions The risk of CMM increases with female sex, older age, abnormal weight, and smoking. Additionally, CMM is associated with a higher likelihood of having hypertension. Efforts targeting high-risk populations with modifiable CMM related-risk factors are crucial for prevention of CMM.Figure 1.Risk factors for CMM

Hair cortisol concentration, a biomarker of stress, is gradually increased in patients with acute myocardial infarction before the acute episode

Abstract Background/Introduction Chronic stress is considered to be an important element of residual cardiovascular risk and modern guidelines recommend its systematic assessment and treatment. Its pathophysiologic contribution, however, in acute myocardial infarction (AMI) was not, until recently, easy to elucidate. This arises from difficulties in objectively quantifying stress levels using conventional research methods, like questionnaires. Purpose The purpose of our study was to measure stress levels at the days preceding an acute myocardial infarction using a solid biomarker, Hair Cortisol Concentration (HCC). Methods 102 consecutive patients with AMI (71 patients with ST-elevation Myocardial Infarction [STEMI] and 31 with Non ST-elevation Myocardial Infarction) from our institution were recruited for this study. We took hair samples from them to precisely measure HCC, which reflects cumulative cortisol levels for the time period preceding the acute event. We also did full clinical, biochemical and psychological evaluation. HCC levels were then compared with 50 age-matched healthy controls. Results To assess the temporal trend of HCC in hair segments, corresponding to specific time periods, we fitted linear mixed models. The mixed effects linear model including the main effects of time and group (AMI versus controls) and their interaction showed that cortisol concentration in hair increased over time with higher rate of increase in AMI patients versus controls (beta of interaction = 3.57; 95%CI: 1.74, 5.40; p < 0.001) The model explained a high percentage of the variance (conditional R2=0.940). No other baseline variable had a significant effect when added to the basic model. There was no significant difference between STEMI and NSTEMI (beta of interaction = 1.15; 95%CI: -1.330, 3.59; p = 0.358) Conclusions Hair cortisol levels, presumably reflecting stress levels, were gradually increasing before an acute myocardial infarction with higher rate of increase in patients compared to healthy controls. There was no significant difference between STEMI and NSTEMI patients. Picture 1. Predicted hair concentrations of cortisol over time prior to the event, based on linear mixed models.

Characterisation of the pharmacokinetic and pharmacodynamic relationship of milvexian in total knee replacement patients

Abstract Background Milvexian, an oral factor XIa inhibitor, is currently being evaluated in patients at risk for thrombotic events due to atrial fibrillation, ischaemic stroke, or acute coronary syndrome. The exposure-response relationship between clinical efficacy and safety endpoints and milvexian pharmacokinetic (PK) metrics was recently submitted as a separate publication. Characterisation of the relationship between the coagulation pharmacodynamic (PD) markers versus milvexian PK metrics at the patient level has yet to be reported. Purpose This analysis characterised the relationship between the coagulation biomarkers, activated partial thromboplastin time (aPTT) and prothrombin time (PT), and milvexian systemic exposure in patients undergoing total knee replacement (TKR) evaluated in the AXIOMATIC-TKR study. Methods A population pharmacokinetic (PopPK) model was previously developed and characterised the PK of milvexian in TKR patients well. The PK/PD relationships between observed aPTT and PT versus PopPK model estimated time-matched milvexian plasma concentrations via nonlinear mixed effects modeling. The relationship between key clinical safety endpoints (e.g., any bleeding or clinically relevant non-major bleeding) and individual PD marker change (e.g., aPTT ratio to baseline) was also explored. Results The aPTT increased with increasing plasma concentration of milvexian over the range of doses evaluated in the study (25mg QD to 200mg BID). An Emax type of model reasonably characterised the PK/PD relationship between the aPTT and model predicted time-matched milvexian plasma concentration, which is consistent with previously observed relationships in healthy volunteers. No change was observed in PT with increased milvexian exposure. No obvious relationship was identified between any (including clinically relevant non-major) bleeding and aPTT ratio to baseline. Conclusions Increased milvexian exposure is directly correlated with aPTT prolongation over the range of doses evaluated in the TKR study. There was no obvious relationship between any (including clinically relevant non-major) bleeding and aPTT ratio. The PK/PD relationship of aPTT without a parallel relationship in PT distinguishes milvexian, a FXIa inhibitor, from previously studied FXa inhibitors. These analyses were a complementary component in dose selection for the milvexian Phase 3 program. Figure 1. PK/PD relationship between aPTT (left) and PT (right) and estimated time-matched plasma concentration (AXIOMATIC-TKR study)

Missed opportunities of method information index plus (MII+) counseling among current modern contraceptive users. multi-level analysis from the Ethiopian PMA 2021 data set

IntroductionIn Ethiopia, there is a decrease in percentage of women who receive method information index counseling service from 39% (95%CI: 33%, 44%) in 2015 to 12% in 2019 (95% CI: 10%, 14%) nationally, and less than 40% of these services provided are high quality. Therefore, the aim of this study was to identify modern contraceptive users-related factors at individual level and community level associated with missed opportunities of method information index plus counseling.MethodsThis study used the datasets from the 2019 Performance Monitoring for Action Ethiopia Survey, which comprised a total of 8,365 households (98.9%) and 7,988 women (98.8%). The data analysis was done with Stata version 14. Using multilevel mixed effect logistics regression, both individual and community-level factors were found to be associated with missed opportunities of method information index plus counseling. a P-value of less than 0.05 was used to declare statistical significance. The association was presented using an adjusted odds ratio with a 95% confidence interval.ResultsThe study shows that the prevalence of missed opportunity MII + family planning counseling among current modern contraceptive users was 81% (79.15, 82.66) and factors significantly associated with missed opportunities of method information index plus counselling are educational status, low level of media exposure, religion, receiving the service in health centers and health posts, never heard of any other methods, number of children at first contraceptive use and region.ConclusionsIn Ethiopia 81% of women had a missed opportunities of MII + counseling service. In order to address this, we recommend policy makers to focus on training of health care workers and pharmacists about MII + counseling, and establishing ways to improve access to media exposure.

Non-health-targeted promotions and step counts of smartphone-based mall walking program users

Abstract Background The COVID-19 pandemic changed lifestyles and raised concerns regarding physical inactivity among adults. Mobile health interventions for physical activity may be a potential solution. However, the effects may diminish over time. This study investigated whether incorporating non-health-targeted promotions into an existing mobile health-walking program could stimulate users to walk. Methods We used nationwide cohort data of smartphone users participating in a shopping mall walking program in Japan. We focused on existing users registered in the program until October 31, 2022. A Japanese anime tie-in promotion was conducted by the shopping mall company from December 3 to 25, 2022, offering additional rewards alongside the regular program. We collected step count records of existing users 1 month before and after (November 1 to December 2, 2022, and December 26, 2022 to January 31, 2023, respectively), and during the promotion period. Propensity score matching was applied to ensure balance in the baseline characteristics of existing users in terms of gender, age, and pre-promotion program participation frequency. Next, we analyzed the association between participation in the promotion program and the average daily step counts during and after the promotional period using mixed effects models for repeated measures, while adjusting for the same covariates. Results Among the 18,156 users included in the study, 13,386 (73.7%) were women, with a mean (SD) age of 45.2 (12.7) years, and a mean (SD) pre-promotion program participation frequency of 9.7 (9.6) per month. During the promotion period, the participants walked 87 (95% CI: 50-125) more steps per day than non-participants, after adjusting for covariates. No clear association was observed 1 month post-promotion. Conclusions These findings indicate that non-health-targeted promotions may be short-term motivators for existing app users to walk. Ongoing monitoring is necessary to assess the long-term impact. Key messages • Mobile health intervention effects may diminish over time. • A non-health-related promotion could stimulate existing mall walking program app users to increase their daily step count temporarily.

Corporate Social Responsibility and Financial Performance of Nawiri Sacco Society Limited in Embu County, Kenya

This study explored the relationship between Corporate Social Responsibility (CSR) and financial performance in the context of Nawiri Sacco Society Limited in Embu County, Kenya. Given the dynamic nature of CSR and the divergent results from global studies on its impact on financial performance, this research aimed to shed light on whether CSR activities contributed positively to Nawiri Sacco's financial outcomes. Specifically, it examined how stakeholder expectations, regulatory compliance, CSR-related costs and risks, and industry characteristics affected the Sacco’s financial performance. The research employed a regression model to evaluate these factors, with a notable emphasis on how stakeholder pressures and regulatory frameworks shaped CSR's financial implications. Data was collected from 85 executive members through structured questionnaires, achieving an impressive 88.9% response rate, which supported the reliability of the results.The findings indicated a significant relationship between CSR and financial performance, revealing mixed effects among the different CSR factors. For instance, stakeholder expectations showed a negative impact on financial performance, suggesting that while stakeholder engagement was critical, excessive focus could strain financial resources. Conversely, regulatory compliance, cost implications, and industry characteristics demonstrated a positive association, highlighting the potential of CSR to improve financial outcomes when effectively managed. These insights reinforced the need for a balanced CSR strategy that aligned with both social responsibilities and financial goals. This study contributed to existing literature by focusing on a Sacco's CSR practices, adding a unique perspective on how socially responsible initiatives could affect financial performance in cooperative institutions, particularly within the Kenyan context.

MRI-Free Processing of Tau PET images for Early Detection

Abstract Tau PET imaging in Alzheimer’s Disease (AD) is becoming increasingly common to assess in vivo tau burden. MR images are often acquired to assist with processing of PET data including for region-of-interest definitions in native space and for normalization to template space. However, in the real-world setting, corresponding MRIs may not be available and PET processing may require MRI-free pipelines. This is particularly important and challenging as the field moves towards early detection among clinically unimpaired (CU) individuals where changes in tau PET signal are expected to be subtle. We used two independent [18F]Flortaucipir tau PET datasets to evaluate whether MRI-free PET processing can detect subtle tau PET uptake differences in Amyloid+ (A+) CU individuals (preclinical AD) versus A-. Standardized Uptake Value Ratios (SUVRs) from MRI-free compared to MRI-based methods were evaluated using linear regression and linear mixed effects regression models. Effect size differences between A+/- CU groups in MRI-free processed cross-sectional and longitudinal tau PET SUVRs were compared to differences quantified through MRI-based processing. Regional MRI-free SUVRs were highly correlated with MRI-based SUVRs within CU individuals (average ICC = 0.90 for ADNI CU and 0.81 for A4 CU). MRI-free and MRI-based pipelines resulted in similar estimates of cross-sectional and longitudinal differences between A- and A+ CU, even in early focal regions within the medial temporal lobe.

Effects of PACK training on the management of asthma and chronic obstructive pulmonary disease by primary care clinicians during 2 years of implementation in Florianópolis, Brazil: extended follow-up after a pragmatic cluster randomised controlled trial with a stepped-wedge design

BackgroundTraining primary care doctors and nurses to use Practical Approach to Care Kit (PACK) improved management of asthma and chronic obstructive pulmonary disease (COPD) in a previous randomised trial. The...

A Study of Long-Run Equilibrium Relationship Between Foreign Direct Investment and Its Key Determinants in Malaysia

This study investigates the long-run equilibrium relationship between foreign direct investment (FDI) and its key determinants in Malaysia. Employing the Autoregressive Distributed Lag (ARDL) model on annual data between 1971 and 2021. The key findings confirm a long-run equilibrium relationship between FDI and the selected macroeconomic variables as a group. However, the individual impact of gross domestic product, inflation, exchange rate, and trade openness on FDI is not statistically significant when analyzed separately. Specifically, the long-run results suggest that the determinants do not have significant effects on FDI. Meanwhile, the short-run relationship between FDI and its determinants in Malaysia reveals a complex interplay of factors. Inflation and exchange rates play significant roles, with inflation generally encouraging FDI and exchange rate volatility creating mixed effects. Trade openness on the other hand shows some short-run significance but it is not consistently impactful. The error correction (ECM) model also confirms the existence of a long-run relationship. It highlights that while short-term fluctuations can occur, FDI tends to move towards a long-term equilibrium influenced by a relatively moderate speed of adjustment. The key conclusion implies that FDI is influenced by the combined effect of these variables in the longer term, but the individual contribution of each variable is not strong enough to stand out statistically. This research contributes to the understanding of FDI dynamics in Malaysia by providing insights, thereby informing policymakers and investors about effective strategies to attract and leverage FDI for sustainable development.

Population Pharmacokinetic Modelling of Norepinephrine in Healthy Volunteers Prior to and During General Anesthesia.

Intraoperation hypotension (IOH) is commonly observed in patients undergoing surgery under general anesthesia, and even a brief episode of IOH can lead to unfavorable outcomes. To reduce the risk, blood pressure is closely measured during general anesthesia, and norepinephrine (NE) is frequently administered if hypotension is detected. Despite its routine application, information on the dose-exposure-response relationship of NE remains limited. Additionally, quantification of the influence of general anesthesia on the pharmacokinetics (PK) of NE is lacking. In this study, we aimed to describe NE PK in healthy volunteers and the influence of general anesthesia on its PK. A single-center, cross-over study was conducted in healthy volunteers. The volunteers received a step-up NE dosing scheme (0.04, 0.08, 0.12, 0.16 and 0.20 mcg-1/kg-1/min-1) first in the awake state and then under general anesthesia. General anesthesia was administered using a propofol/remifentanil Eleveld target-controlled infusion. During general anesthesia, a 30-second electrical stimulus was given as surrogate for surgical incision to the volunteers at each dosage step. Blood samples were drawn before the initial dosing and after each dosing step, and plasma NE, propofol and remifentanil concentrations were subsequently determined. A population PK model was developed using non-linear mixed effects modelling. Simulations were conducted to predict the plasma NE concentration in patients at different measured propofol concentrations. A total of 1219 samples were analyzed from 36 volunteers. A two-compartment model with a first-order elimination best described the data. Weight, age, and session effect (awake vs general anesthesia) were identified as relevant covariates on the clearance (CL) of NE. A 10% decrease in NE CL was observed after general anesthesia induction. This difference between sessions is better explained by the measured concentration of propofol, rather than the anticipated impact of cardiac output. The estimated post-stimulation NE concentration is 0.66 nmol/L-1 (95% CI 0.06-1.20 nmol/L-1) lower than the pre-stimulation NE concentration. Model simulation indicates that patients at a higher measured propofol concentration (e.g., 6 mcg/mL-1) exhibited higher NE concentrations (95% PI 18.10-43.89 nmol/L-1) than patients at a lower measured propofol concentration (e.g., 3 mcg/mL-1) (95% PI 16.81-38.91 nmol L-1). The NE PK is well described with a two-compartment model with a first-order elimination. NE CL exhibiting a 10% decrease under general anesthesia, with this difference being attributed to the measured concentration of propofol. The impact of stimulation on NE PK under general anesthesia is very limited. NL9312.

Prevalence and Associated Risk Factors of Vitamin D Deficiency Among Female Adolescents in Sulaimaniyah, Iraq: A Community-Based Cross-Sectional Study

Objectives: This study aims to examine the prevalence and risk factors related to VD deficiency among female adolescents. Methods: This cross-sectional study was done in secondary and preparatory schools in Sulaimaniyah, Iraq, from May 2022 to July 2023. A total of 120 schools were included in the study, with a calculated sample size of 340 female adolescents using a probability multistage random sampling method. Data was collected through a validated questionnaire, and blood samples were analyzed for VD levels. Results: In a study of 340 female adolescents aged 14-18 years, the findings showed that 39.4% of participants had severe VD deficiency, 42.6% were deficient, and 17.9% had insufficiency. The mean VD level was 13.29±6.45 ng/mL. Seasonal variation significantly impacted VD level (p=0.001), with the highest levels seen in summer and the lowest in winter. Skin colour also significantly influenced VD level (p=0.020), as individuals with lighter skin have higher levels. There were positive correlations between VD levels, milk intake (r=0.138, p=0.011), and cheese consumption (r = 0.135, p=0.013). The use of sunscreen had mixed effects. Interestingly, there was a positive correlation between SPF 15 and VD level (r=0.132, p=0.015), while higher SPF values were associated with lower levels. Conclusion: The findings highlight the importance of seasonal adjustments, improved dietary habits, and lifestyle changes to address VD deficiency in the population effectively.

Flexible Bayesian modeling for longitudinal binary and ordinal responses

Longitudinal studies with binary or ordinal responses are widely encountered in various disciplines, where the primary focus is on the temporal evolution of the probability of each response category. Traditional approaches build from the generalized mixed effects modeling framework. Even amplified with nonparametric priors placed on the fixed or random effects, such models are restrictive due to the implied assumptions on the marginal expectation and covariance structure of the responses. We tackle the problem from a functional data analysis perspective, treating the observations for each subject as realizations from subject-specific stochastic processes at the measured times. We develop the methodology focusing initially on binary responses, for which we assume the stochastic processes have Binomial marginal distributions. Leveraging the logits representation, we model the discrete space processes through continuous space processes. We utilize a hierarchical framework to model the mean and covariance kernel of the continuous space processes nonparametrically and simultaneously through a Gaussian process prior and an Inverse-Wishart process prior, respectively. The prior structure results in flexible inference for the evolution and correlation of binary responses, while allowing for borrowing of strength across all subjects. The modeling approach can be naturally extended to ordinal responses. Here, the continuation-ratio logits factorization of the multinomial distribution is key for efficient modeling and inference, including a practical way of dealing with unbalanced longitudinal data. The methodology is illustrated with synthetic data examples and an analysis of college students’ mental health status data.

Technology-assisted instruction with teacher prompts on fraction multiplication word problems: A single-case design with visual analysis and Bayesian multilevel modeling

ABSTRACT This study examines the effects of technology-assisted instruction with teacher prompts on the ability to visualize and solve fraction multiplication word problems for four middle school students with learning disabilities. A multiple-probe design across participants, a type of single-case design, showed a functional relationship between the intervention and the targeted mathematical outcomes. Although there were some fluctuations over time, students demonstrated improvements from the baseline to intervention phases (Tau ranged from 0.76 to 1.00 for visualization and was 1.00 for problem-solving). Researchers employed Bayesian cumulative link mixed effects models to examine the moderating effects of word problem question types. Students showed greater maintenance effects on problem-solving than on visualization tasks, as reflected in changes in level (logit coefficient = 2.6) and trend (logit coefficient = 0.22). Students and teachers perceived vocabulary and multiplication fact practices, as well as the cognitive and metacognitive features embedded in the technology-assisted intervention, to be useful in learning targeted mathematics concepts. This study underscores the role of technology integration in enhancing teachers’ instructional approach and in aiding students’ acquisition and retention of mathematical concepts and skills.

Regional variation in the landscape ecology of West Nile virus sentinel chicken seroconversion in Florida.

How landscape composition and configuration impact the distribution of multi-vector and multi-host mosquito vector-borne disease systems, such as West Nile virus (WNV), remains challenging because of complex habitat and resource requirements by hosts and vectors that affect transmission opportunities. We examined correlations between landscape composition and configuration and 2018 WNV sentinel chicken seroconversion in Florida, USA across the state and within five National Oceanic Atmospheric Administration (NOAA) bioclimatic regions to understand strength and variation of landscape effects during an elevated transmission year. Although few landscape studies have examined WNV in Florida, we expected higher percentages of residential or medium-developed landscapes and more fragmented landscapes would be positively correlated with WNV seroconversion owing to the main mosquito vector habitats and avian host distributions. However, we expected to find variation in the importance of forest, wetland, and agriculture landscapes across bioclimatic regions in the state. WNV seroconversion rates were calculated using Florida 2018 Department of Health WNV sentinel chicken seroconversion data from 187 flocks maintained by mosquito control programs. Percent land cover and edge density metrics were calculated for multiple land cover classes and within multiple buffer distances from chicken coops using 2019 National Land Cover Data. We used binomial generalized linear mixed effects models to calculate the importance of landscape metrics to WNV seroconversion. We found no statewide predictors of seroconversion, but as expected, the importance of landscape varied across regions. In the north-central part of the state, we found higher seroconversion in less populated suburban areas while higher seroconversion in south-central Florida was correlated with fragmented forested areas within 0.5 km of coops and intact woody wetland areas within 2 km of coops. This work corroborates previous findings that consistent landscape predictors of WNV are difficult to identify across broader geographic areas and sets the stage for additional work that incorporates climate and landscapes interactions for a greater understanding of WNV ecology in this geographic region.

Longitudinal mediation analysis with multilevel and latent growth models: a separable effects causal approach

BackgroundCausal mediation analysis is widespread in applied medical research, especially in longitudinal settings. However, estimating natural mediational effects in such contexts is often difficult because of the presence of post-treatment confounding. Moreover, many models frequently used in applied research, like multilevel and latent growth models, present an additional difficulty, i.e. the presence of latent variables. In this paper, we propose a causal interpretation of these two classes of models based on a novel type of causal effects called separable, which overcome some of the issues of natural effects.MethodsWe formally derive conditions for the identifiability of separable mediational effects and their analytical expressions based on the g-formula. We carry out a simulation study to investigate how moderate and severe model misspecification, as well as violation of the identfiability assumptions, affect estimates. We also present an application to real data.ResultsThe results show how model misspecification impacts the estimates of mediational effects, particularly in the case of severe misspecification, and that the bias worsens over time. The violation of assumptions affects separable effect estimates in a very different way for the mixed effect and the latent growth models.ConclusionOur approach allows us to give multilevel and latent growth models an appealing causal interpretation based on separable effects. The simulation study shows that model misspecification can heavily impact effect estimates, highlighting the importance of careful model choice.

Simultaneous Fixed and Random Effects Selection in Order-restricted Mixed Effects Models

When dealing with longitudinal data, if we directly select a specific model for modeling without any prior information about the existence of significant random effects before utilizing the mixed model, it may result in the misuse of the model, thereby affecting the final estimation results. This paper investigates a variable selection method that can jointly select both fixed and random effects in Bayesian mixed model under order constraints. This method can effectively prevent model misuse. A computationally feasible Gibbs algorithm is proposed for posterior inference. The performance of our proposal is evaluated by simulated data and two real applications related to Blood lead levels and Ramus bone heights. Results show that the proposed approaches perform very well in various situations.

Variation in diurnal and nocturnal movements distances revealed in wintering dabbling ducks in the Mississippi Alluvial Valley

Movement of waterfowl during winter is central to resource acquisition and mortality avoidance, despite the imminent risk to survival and overall fitness induced by hunting disturbance and energy expenditure. Weather and other environmental conditions may influence movement by altering resource needs, in which ducks must balance the trade‐offs of resource acquisition and risk management. We compared how environmental factors influenced total daily diurnal and nocturnal movement distances of three dabbling duck species wintering in the Mississippi Alluvial Valley. We estimated total daily diurnal and nocturnal movement distances of green‐winged teal (Anas crecca; n = 51), American wigeon (Mareca americana; n = 38), and mallards (Anas platyrhynchos; n = 31) using backpack transmitters during the winter period of February–November 2020–2021 and 2021–2022. We used linear mixed effects models to model the influence of weather, hunt season, day of season, and sex on total diurnal and nocturnal movement distances by species. Green‐winged teal moved 7.7% further during the nocturnal period (x̅ = 3.38 km; SE = 0.32; p < 0.001) than during the diurnal period (x̅ = 3.13 km SE = 0.10), while American wigeon and mallards moved 36.6% (x̅ = 4.95 km; SE = 0.20; p < 0.001) and 28.1% (x̅ = 4.39 km; SE = 0.23; p < 0.001) further during the diurnal period than the nocturnal period (x̅ = 3.42 km, SE = 0.28 and x̅ = 3.31 km, SE = 0.22), respectively. Fine‐scale movement distances during the diurnal period were weakly associated with environmental covariates for all species. Conversely, moon illumination influenced nocturnal movement distances for all species. Nightly movement distances of mallards increased by 2.1 times from new to full moon during the hunting season. Conversely, there were no changes in nocturnal movement distance during pre‐hunt and post‐hunt periods when hunting disturbance was absent. In the face of intensifying environmental pressures on movement patterns in dabbling duck populations, this research demonstrates a behavioral response to moon illumination as a mechanism for moving about the landscape for resource acquisition in the presence of human disturbances that induce risk, such as hunting.

Incidence of Concurrent Cerebral Desaturation and Electroencephalographic Burst Suppression in Cardiac Surgery Patients.

Increased intraoperative electroencephalographic (EEG) burst suppression is associated with postoperative delirium. Cerebral desaturation is considered as one of the factors associated with burst suppression. Our study investigates the association between cerebral desaturation and burst suppression by analyzing their concurrence. Additionally, we aim to examine their association with cardiac surgical phases to identify potential for targeted interventions. We retrospectively analyzed intraoperative 1-minute interval observations in 51 patients undergoing cardiac surgery. Processed EEG and cerebral oximetry were collected, with the anesthesiologists blinded to the information. The associations between cerebral desaturation (defined as a 10% decrease from baseline) and burst suppression, as well as with phase of cardiac surgery, were analyzed using the Generalized Logistic Mixed Effect Model. The results were presented as odds ratio and 95% confidence intervals (CIs). A value of P < .05 was considered statistically significant. The odds of burst suppression increased 1.5 times with cerebral desaturation (odds ratio [OR], 1.52, 95% CI, 1.11-2.07; P = .009). Compared to precardiopulmonary bypass (pre-CPB), the odds of cerebral desaturation were notably higher during CPB (OR, 22.1, 95% CI, 12.4-39.2; P < .001) and post-CPB (OR, 18.2, 95% CI, 12.2-27.3; P < .001). However, the odds of burst suppression were lower during post-CPB (OR, 0.69, 95% CI, 0.59-0.81; P < .001) compared to pre-CPB. Compared to pre-CPB, the odds of concurrent cerebral desaturation and burst suppression were notably higher during CPB (OR, 52.3, 95% CI, 19.5-140; P < .001) and post-CPB (OR, 12.7, 95% CI, 6.39-25.2; P < .001). During CPB, the odds of cerebral desaturation (OR, 6.59, 95% CI, 3.62-12; P < .001) and concurrent cerebral desaturation and burst suppression (OR, 10, 95% CI, 4.01-25.1; P < .001) were higher in the period between removal of aortic cross-clamp and end of CPB. During the entire surgery, the odds of burst suppression increased 8 times with higher inhalational anesthesia concentration (OR, 7.81, 95% CI, 6.26-9.74; P < .001 per 0.1% increase). Cerebral desaturation is associated with intraoperative burst suppression during cardiac surgery, most significantly during CPB, especially during the period between the removal of the aortic cross-clamp and end of CPB. Further exploration with simultaneous cerebral oximetry and EEG monitoring is required to determine the causes of burst suppression. Targeted interventions to address cerebral desaturation may assist in mitigating burst suppression and consequently enhance postoperative cognitive function.