Bayesian Linear Mixed Effects Models Research Articles

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

Data aggregation can lead to biased inferences in Bayesian linear mixed models and Bayesian analysis of variance.

Bayesian linear mixed-effects models (LMMs) and Bayesian analysis of variance (ANOVA) are increasingly being used in the cognitive sciences to perform null hypothesis tests, where a null hypothesis that an effect is zero is compared with an alternative hypothesis that the effect exists and is different from zero. While software tools for Bayes factor null hypothesis tests are easily accessible, how to specify the data and the model correctly is often not clear. In Bayesian approaches, many authors use data aggregation at the by-subject level and estimate Bayes factors on aggregated data. Here, we use simulation-based calibration for model inference applied to several example experimental designs to demonstrate that, as with frequentist analysis, such null hypothesis tests on aggregated data can be problematic in Bayesian analysis. Specifically, when random slope variances differ (i.e., violated sphericity assumption), Bayes factors are too conservative for contrasts where the variance is small and they are too liberal for contrasts where the variance is large. Running Bayesian ANOVA on aggregated data can-if the sphericity assumption is violated-likewise lead to biased Bayes factor results. Moreover, Bayes factors for by-subject aggregated data are biased (too liberal) when random item slope variance is present but ignored in the analysis. These problems can be circumvented or reduced by running Bayesian LMMs on nonaggregated data such as on individual trials, and by explicitly modeling the full random effects structure. Reproducible code is available from https://osf.io/mjf47/. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mixed language in flux? The various impacts of multilingual contact on Lánnang-uè’s wh-question system

Aims and objectives: What exactly happens to a mixed language’s system in a multilingual contact setting? This study aims to investigate the interactions between speakers’ exposure to, frequency of, and proficiency in four languages (English, Tagalog, Hokkien, and Mandarin) and their influences on the why-fronting only wh-question system of Lánnang-uè, a mixed language used by the metropolitan Manila Lannangs. It also aims to test the validity of the assertion that symbiotic mixed languages are more likely to be in flux. Methodology: The Lánnang-uè speakers participated in production and acceptability experiments. Data analysis: Likelihood to front (production) and responses to a 7-point Likert-type scale (acceptability) were the dependent variables for several Bayesian linear mixed-effects models with age, frequency of language use, and language proficiency as primary fixed effects, sociolinguistic factors (e.g., attitudes, identity) as covariates, and participant (and when appropriate, item) as a random effect. Findings: Both production and acceptability results showed that the effects of contact are numerous and far from homogeneous. They vary depending on the source language, wh-phrase type, and degree of consciousness. They corroborate the widely held belief that mixed languages are more stable in symbiotic contexts. However, this paper goes an extra step to show that this “instability” or variability is not always a consequence of contact-induced transfer. It demonstrates that when the source languages influence the stability or development of the mixed language, the effects can be diverse, encompassing aspects such as identity processes, language attitudes, structural transfer, and/or other sociolinguistic innovations. Originality: This article is one of the first studies to examine the effects of contact between multiple languages on a mixed language variable using both production and acceptability experimental data in a five-language context. It is one of the very few variationist works in the Philippines that considers the effects of multilingualism on variation and change.

County‐level cumulative effect of ambient PM2.5 exposure on the Alzheimer’s disease mortality rate in the west coast regions of the United States

AbstractBackgroundSeveral studies have investigated the relationship between long‐term exposure to fine particulate matter (PM2.5) and the risk of Alzheimer’s disease (AD), yet studies on the cumulative effect of PM2.5 exposure are limited. This study assesses the association between the county‐level cumulative PM2.5 exposure at a level above 35 ug/m3, the safe threshold recommended by the World Health Organization (WHO), on Alzheimer’s mortality in the west coast population of the United States.MethodAnnual county‐level Alzheimer’s disease mortality rates from 2010 to 2019 were obtained from the Centers for Disease Control and Prevention WONDER database, and the cumulative county‐level PM2.5 exposure greater than 35 ug/m3 were derived from publicly accessible data at the Environmental Protection Agency (EPA). Analysis focused on 76 counties for about 48 million people in the states of Washington, Oregon, and California of the US.Analysis was conducted using a Bayesian spatiotemporal linear mixed effects model with the Markov Chain Monte Carlo Simulations. For each county, the log transformed county‐level annual AD mortality rates were regressed against the total number of days with concentration levels of PM2.5 over 35 ug/m3 in the year and its past t years, where t = 1, 2, …, 10 (Figure 1 for t = 10). Each of the 10 regression models was adjusted for thirteen potentially confounding variables including the rate of poverty, percent rural land area, median household income, percent unemployed, percent uninsured, percent obesity, percent smokers, percent excessive drinking, percent African American, percent Asian, percent Hispanic, percent ages under 18, and percent ages 65 and older.ResultResults showed that in periods of three calendar years or longer, having a higher number of days of PM2.5 exceeding the safe level is associated with a higher rate of AD mortality (Figure 2). The results also showed an increasing trend between AD mortality and years of cumulative PM2.5 exposure.ConclusionCumulative PM2.5 exposure at a level above the WHO recommended safe threshold is associated with AD mortality rate in three west coast states of the US.

Preliminary investigation of semantic memory assessments in Colombian adults with and without post-stroke aphasia

PurposeThis work evaluates clinical-standard semantic memory assessments in monolingual Spanish-speaking Colombian adults with and without aphasia, addressing 2 aims: (1) to examine whether event semantic memory is related to object and action semantic memory performance; and (2) to explore whether clinical-standard semantic memory assessments can distinguish between Colombian adults with and without aphasia. MethodsObject, action, and event semantic memory clinical assessments were used evaluate 16 adults with aphasia and 16 matched controls from Colombia. Bayesian linear mixed-effects models were used to examine the 2 specific aims. ResultsFirst, results replicated and extended findings that object and action deficits may contribute to event semantic memory impairments in aphasia. Second, results suggested that clinical-standard semantic memory assessments may distinguish between people with and without post-stroke aphasia in a Colombian sample. ConclusionThis work identifies the need to continue developing sociolinguistically sensitive neuropsychological assessments, which are critical for establishing valid cognitive models and improving clinical diagnostics and treatments in diverse populations of stroke survivors.

Pinpointing change in virtual reality assisted treatment for violent offenders: a pilot study of Virtual Reality Aggression Prevention Training (VRAPT).

Preventing relapse into violence and its destructive consequences among persistent re-offenders is a primary concern in forensic settings. The Risk-Need-Responsivity framework models the best current practice for offender treatment, focused on building skills and changing pro-criminal cognitions. However, treatment effects are often modest, and the forensic context can obstruct the delivery of interventions. Developing treatments for offenders should focus on the best method of delivery to make "what works work." Virtual reality (VR)-assisted treatments such as Virtual Reality Aggression Prevention Training (VRAPT) are a new and innovative approach to offender treatment. This pilot study followed 14 male violent offenders who participated in VRAPT in a Swedish prison context and measured changes from pre-treatment to post-treatment and 3-month follow-up in targeted aggression, emotion regulation, and anger. It also investigated potential impact factors (pro-criminal cognitions, externalizing behaviors, psychosocial background, and childhood adverse experiences). In Bayesian linear mixed effects models, participants showed a high probability of change from pre-treatment to post-treatment and to follow-up on all outcome measures. All outcome measures demonstrated a low probability of change from post-treatment to follow-up. Analysis of reliable change showed that participants' results ranged from recovery to deterioration. We discuss the implications of the study for VRAPT's impact on the target group, those who might benefit from the approach, and suggested foci for future studies in the field of VR-assisted offender treatment. The study was preregistered at the International Standard Randomized Controlled Trial Number registry (https://doi.org/10.1186/ISRCTN14916410).

The Potential Impacts of Statins and Beta-Blockers on West Virginia Ichthyofauna

Pharmaceuticals and personal care products (PPCPs), such as statins and beta-blockers, are commonly used to treat cardiovascular disease in adults. Active versions of these pharmaceuticals and their various metabolites enter surface waters via wastewater treatment plant (WWTP) discharge, as well as from other point sources. Sub-lethal effects of statins and beta-blockers on wild fish at environmental concentrations have been understudied up to this point. The objectives of this study were to use several health condition metrics and determine if there was a relationship between fish condition and environment concentrations of statins and beta-blockers near two West Virginia WWTPs. Water samples were collected from upstream, downstream, and effluent pipe from August to November 2022, and analyzed for atorvastatin, simvastatin, metoprolol, and carvedilol via liquid chromatography with tandem mass spectrometry. Fish were sampled upstream, at the discharge, and downstream of each WWTP in November 2022. Fish health was assessed with three metrics: relative weight (Wr), hepatosomatic index (HSI), and gonadosomatic index (GSI). ANOVAs were used to assess differences among the health metrics based on sex, genus/species, and location relative to WWTPs. Additionally, changes in Wr relative to surface water concentrations of statins and beta-blockers was modeled with a Bayesian linear mixed effects model, with surface water concentrations as fixed effects with a random slope, while the section and genus parameters were treated as random intercepts. Surface concentrations for atorvastatin (0.47–4.36 ng/L), simvastatin (0.27–0.95 ng/L), metoprolol (2.80–21.01 ng/L), and carvedilol (0.43–0.90 ng/L) varied across sampling sections. HSI based on sex and species were nearly significant. GSI was significantly higher in females. Wr differed among genera, as well as the interaction between genus and sample section (p < 0.001). Fixed effects from the linear mixed effects model showed Wr was negatively related to simvastatin (−0.139 [−2.072–1.784]) and carvedilol (−0.262 [−2.164–1.682]) while atorvastatin (0.207 [−1.371–1.845]) and metoprolol (0.052 [−0.533–0.584]) were positively related to Wr. Individual genera responded differently to each pharmaceutical based on location, indicating that it is likely that other factors were also influencing the fish health metrics. Further research targeting individual tissues and controlled experiments with different exposure regimes will be required to further enlighten the long-term effects of cardiovascular PPCPs on fish health.

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa.

The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN. Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models. Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females. This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

Letter-similarity effects in braille word recognition.

Letter-similarity effects are elusive with common words in lexical decision experiments: viotin and viocin (base word: violin) produce similar error rates and rejection latencies. However, they are robust for stimuli often presented with the same appearance (e.g., misspelled logotypes such as anazon [base word: amazon] produce more errors and longer latencies than atazon). Here, we examine whether letter-similarity effects occur in reading braille. The rationale is that braille is a writing system in which the sensory information is processed in qualitatively different ways than in visual reading: the form of the word's letters is highly stable due to the standardisation of braille and the sensing of characters is transient and somewhat serial. Hence, we hypothesised that the letter similarity effect would be sizable with misspelled common words in braille, unlike the visual modality. To test this hypothesis, we conducted a lexical decision experiment with blind adult braille readers. Pseudowords were created by replacing one letter of a word with a tactually similar or dissimilar letter in braille following a tactile similarity matrix (e.g., [ausor] vs [aucor]; baseword: [autor]). Bayesian linear mixed-effects models showed that the responses to tactually similar pseudowords were less accurate than to tactually dissimilar pseudowords-the response times (RTs) showed a parallel trend. This finding supports the idea that, when reading braille, the mapping of input information onto abstract letter representations is done through a noisy channel.

Like Father, Like Child? Paternal Age at Birth and Offspring’s Facial Asymmetry and Distinctiveness

Paternal age at birth, a potential proxy of mutation load transmitted to the offspring, has previously been related to the offspring’s health, biological condition and reproductive potential. As higher facial asymmetry and distinctiveness serve as putative markers of the lower genetic quality of an individual, we hypothesize that more advanced paternal age at birth will be related to children’s higher levels of facial asymmetry and distinctiveness. To the best of our knowledge, this is the first study evaluating the link between paternal age at birth and facial asymmetry in offspring. Based on archived photographs of 159 children born within 47 Polish families, we have conducted facial geometric morphometric measurements and calculated the levels of facial asymmetry and distinctiveness. The relationship between paternal age at birth and the offspring’s facial features was explored with the use of Bayesian Linear Mixed-effects Models, controlling for sex, age and birth order of the offspring, and maternal age at child’s birth. No associations between paternal age at birth and facial asymmetry or distinctiveness in children were found. The lack of such a relationship might be a result of the potentially insufficient influence of newly accumulated paternal mutations affecting the offspring’s phenotype or higher importance of maternal (prenatal) and postnatal environments in shaping facial features.

An examination of atypical primary progressive aphasia variants

AbstractBackgroundThe Neurodegenerative Research Group (NRG) at Mayo clinic has followed patients with degenerative speech and/or language disorders for over a decade. In this presentation I will present data from this cohort to inform a broader discussion about the importance of apraxia of speech (AOS) and its subtypes, heterogeneity within the agrammatic PPA variant, and perils of mixed phenotypes.MethodWe reviewed the NRG database to identify patients who initially presented with isolated (PPAOS), AOS in conjunction with agrammatic aphasia (AOS‐PAA), isolated agrammatic aphasia (PAA), and patients who had PAA or AOS overlapping with another degenerative diagnosis. Data from the following clinical instruments were abstracted: WAB AQ (aphasia severity), UPDRS III (parkinsonism), WAB Praxis (ideomotor apraxia), and the MoCA (cognitive ability). We assessed the effect of baseline diagnosis and AOS subtype on these outcomes over time using Bayesian linear mixed effects models. We qualitatively reviewed longitudinal diagnostic trajectories. Preliminary analyses were done on available autopsy data.ResultPAA was associated with greater aphasia at baseline and more rapid decline; PPAOS was associated with normal language at baseline and slow decline; and PAA‐AOS with intermediate baseline aphasia and decline. However, for those with AOS longitudinal decline differed based on AOS subtype: prosodic PPAOS was associated with the slowest decline and phonetic PAA‐AOS with the fastest. Some patients met criteria for non‐PPA disorders during follow up. However, compared to patients who met criteria for these disorders at enrollment, the speech/language‐first patients remained qualitatively distinct, and neither resembled the cases that were mixed at onset. Preliminary autopsy data suggests that AOS is predictive of tau and that the specific tauopathy may be related to the initial syndrome and AOS subtype.ConclusionThe differences between PAA, PAA‐AOS and PPAOS suggest that these disorders should not be lumped. In fact, the longitudinal trajectories are sufficiently different that doing so would add noise to observational and interventional studies. Instead, more detailed phenotyping, including AOS subtype, can aid prognostication and may improve prediction of the underlying pathology. Finally, caution should be exercised when considering PPAOS and PPA patients for other FTLD diagnostic categories.

Bayes Factors for Mixed Models

Although Bayesian linear mixed effects models are increasingly popular for analysis of within-subject designs in psychology and other fields, there remains considerable ambiguity on the most appropriate Bayes factor hypothesis test to quantify the degree to which the data support the presence or absence of an experimental effect. Specifically, different choices for both the null model and the alternative model are possible, and each choice constitutes a different definition of an effect resulting in a different test outcome. We outline the common approaches and focus on the impact of aggregation, the effect of measurement error, the choice of prior distribution, and the detection of interactions. For concreteness, three example scenarios showcase how seemingly innocuous choices can lead to dramatic differences in statistical evidence. We hope this work will facilitate a more explicit discussion about best practices in Bayes factor hypothesis testing in mixed models.

Diffusion tensor imaging analysis in three progressive supranuclear palsy variants

Clinical variants of progressive supranuclear palsy (PSP) include the classic Richardson's syndrome (PSP-RS), as well as cortical presentations such as PSP-speech/language (PSP-SL) and subcortical presentations such as PSP-parkinsonism (PSP-P). Patterns of white matter tract degeneration underlying these variants, and the degree to which white matter patterns could differentiate these variants, is unclear. Forty-nine PSP patients (28 PSP-RS, 12 PSP-P, and 9 PSP-SL) were recruited by the Neurodegenerative Research Group and underwent diffusion tensor imaging. Regional diffusion tensor imaging metrics were compared across PSP variants using Bayesian linear mixed-effects models, with inter-variant differentiation assessed using the area under the receiver operator characteristic curve (AUROC). All three variants showed degeneration of the body of the corpus callosum, posterior thalamic radiation, superior cerebellar peduncle, internal and external capsule, and superior fronto-occipital fasciculus. PSP-RS showed greater degeneration of superior cerebellar peduncle compared to PSP-P and PSP-SL, whereas PSP-SL showed greater degeneration of body and genu of the corpus callosum, internal capsule, external capsule, and superior longitudinal fasciculus compared to the other variants. Fractional anisotropy in body of the corpus callosum provided excellent differentiation of PSP-SL from both PSP-P and PSP-RS (AUROC = 0.91 and 0.92, respectively). Moderate differentiation of PSP-RS and PSP-P was achieved with fractional anisotropy in superior fronto-occipital fasciculus (AUROC = 0.68) and mean diffusivity in the superior cerebellar peduncle (AUROC = 0.65). In this pilot study, patterns of white matter tract degeneration differed across PSP-RS, PSP-SL, and PSP-P, with the body of the corpus callosum showing some utility in the differentiation of PSP-SL from the other two variants.

The Impact of COVID-19 on Students' Marks: A Bayesian Hierarchical Modeling Approach.

Due to COVID-19, universities across Canada were forced to undergo a transition from classroom-based face-to-face learning and invigilated assessments to online-based learning and non-invigilated assessments. This study attempts to empirically measure the impact of COVID-19 on students’ marks from eleven science, technology, engineering, and mathematics (STEM) courses using a Bayesian linear mixed effects model fitted to longitudinal data. The Bayesian linear mixed effects model is designed for this application which allows student-specific error variances to vary. The novel Bayesian missing value imputation method is flexible which seamlessly generates missing values given complete data. We observed an increase in overall average marks for the courses requiring lower-level cognitive skills according to Bloom’s Taxonomy and a decrease in marks for the courses requiring higher-level cognitive skills, where larger changes in marks were observed for the underachieving students. About half of the disengaged students who did not participate in any course assessments after the transition to online delivery were in special support.

Stimulus novelty, task demands, and strategy use in episodic memory.

Cognitive task performance is a dynamic process that evolves over time, starting from the first encounters with a task. An important aspect of these task dynamics is the employment of strategies to support successful performance and task acquisition. Focusing on episodic memory performance, we: (1) tested two hypotheses on the effects of novelty and task difficulty on strategy use, (2) replicated our previous results regarding strategy use in a novel memory task, and (3) evaluated whether repeated open-ended strategy queries affect task performance and/or strategy use. The present pre-registered online study comprised 161 adult participants who were recruited through the Prolific crowdsourcing platform. We employed two separate 5-block list learning tasks, one with 10 pseudowords and the other with 18 common nouns, and collected recall performance and strategy reports for each block. Using Bayesian linear mixed effects models, the present findings (1) provide some support for the hypothesis that task-initial strategy development is not triggered only by task novelty, but can appear also in a familiar, moderately demanding task; (2) replicate earlier findings from an adaptive working memory task indicating strategy use from the beginning of a task, associations between strategy use and objective task performance, and only modest agreement between open-ended versus list-based strategy reports; and (3) indicate that repeated open-ended strategy reports do not affect objective recall. We conclude that strategy use is an important aspect of memory performance right from the start of a task, and it undergoes development at the initial stages depending on task characteristics. In a larger perspective, the present results concur with the views of skill learning and adaptivity in cognitive task performance.

Microbial community structure across grazing treatments and environmental gradients in the Serengeti

As one of the last remaining naturally grazed ecosystems on Earth, the Serengeti National Park is an ideal location to study the influence of migratory mammals on the structure of microbial communities and the factors that generate biogeography of soil microbes. Furthermore, volcanic inputs generate environmental gradients that may also structure microbial communities. We studied 16S rRNA amplicons in a 13-year herbivore removal experiment to examine the influence of grazing and environmental gradients on the natural distribution of soil microbes. Removal of mammalian herbivores shifted microbial community structure, with 31 taxa that were significant indicator taxa of the ungrazed treatment and three taxa that were indicators of the grazed treatment. The abundance of many taxa were correlated with soil texture, phosphorus, iron, calcium and rainfall, and the evenness of taxa within samples was also correlated with these variables. Bayesian general linear mixed effects models with single predictors of multiple, highly correlated variables of beta diversity were consistent with a significant, but weak (2%), effect of grazing, and stronger effects of phosphorus (14%). Beta diversity of microbial communities was greater in grazed than in ungrazed plots; suggesting that the impacts of grazing on community assembly of microbes results from deterministic environmental filtering caused by the influence of herbivores on plant communities and soil properties rather than stochastic dispersal via herds of large mammals. These herbivore effects are superimposed on deterministic environmental filtering by natural soil and precipitation gradients across the Serengeti.

Rates of Brain Atrophy Across Disease Stages in Familial Frontotemporal Dementia Associated With MAPT, GRN, and C9orf72 Pathogenic Variants

Several clinical trials are planned for familial forms of frontotemporal lobar degeneration (f-FTLD). Precise modeling of brain atrophy in f-FTLD could improve the power to detect a treatment effect. To characterize regions and rates of atrophy in the 3 primary f-FTLD genetic groups (MAPT, GRN, and C9orf72) across all disease stages from asymptomatic to dementia. This investigation was a case-control study of participants enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration or Longitudinal Evaluation of Familial Frontotemporal Dementia studies. The study took place at 18 North American academic medical centers between January 2009 and September 2018. Participants with f-FTLD (n = 100) with a known pathogenic variant (MAPT [n = 28], GRN [n = 33], or C9orf72 [n = 39]) were grouped according to disease stage (ie, Clinical Dementia Rating [CDR] plus National Alzheimer's Coordinating Center [NACC] FTLD module). Included were participants with at least 2 structural magnetic resonance images at presymptomatic (CDR + NACC FTLD = 0 [n = 57]), mild or questionable (CDR + NACC FTLD = 0.5 [n = 15]), or symptomatic (CDR + NACC FTLD = ≥1 [n = 28]) disease stages. The control group included family members of known pathogenic variant carriers who did not carry the pathogenic variant (n = 60). This study fitted bayesian linear mixed-effects models in each voxel of the brain to quantify the rate of atrophy in each of the 3 genes, at each of the 3 disease stages, compared with controls. The study also analyzed rates of clinical decline in each of these groups, as measured by the CDR + NACC FTLD box score. The sample included 100 participants with f-FTLD with a known pathogenic variant (mean [SD] age, 50.48 [13.78] years; 53 [53%] female) and 60 family members of known pathogenic variant carriers who did not carry the pathogenic variant (mean [SD] age, 47.51 [12.43] years; 36 [60%] female). MAPT and GRN pathogenic variants were associated with increased rates of volume loss compared with controls at all stages of disease. In MAPT pathogenic variant carriers, statistically significant regions of accelerated volume loss compared with controls were identified in temporal regions bilaterally in the presymptomatic stage, with global spread in the symptomatic stage. For example, mean [SD] rates of atrophy in the left temporal were -231 [47] mm3 per year during the presymptomatic stage, -381 [208] mm3 per year during the mild stage, and -1485 [1025] mm3 per year during the symptomatic stage (P < .05). GRN pathogenic variant carriers generally had minimal increases in atrophy rates between the presymptomatic and mild stages, with rapid increases in atrophy rates in the symptomatic stages. For example, in the right frontal lobes, annualized volume loss was -267 [81] mm3 per year in the presymptomatic stage and -182 [90] mm3 per year in the mild stage, but -1169 [555] mm3 per year in the symptomatic stage. Compared with the other groups, C9orf72 expansion carriers showed minimal increases in rate of volume loss with disease progression. For example, the mean (SD) annualized rates of atrophy in the right frontal lobe in C9orf72 expansion carriers was -272 (118) mm3 per year in presymptomatic stages, -310 (189) mm3 per year in mildly symptomatic stages, and -251 (145) mm3 per year in symptomatic stages. These findings are relevant to clinical trial planning and suggest that the mechanism by which C9orf72 pathogenic variants lead to symptoms may be fundamentally different from the mechanisms associated with other pathogenic variants.

The essential value of the alternatives of the suboptimal choice procedure is different for pigeons and rats

Suboptimal choice is the preference for a discriminative alternative with low probability of reinforcement, over a non-discriminative alternative with higher probability of reinforcement. Pigeons consistently prefer the discriminative alternative, whereas rats prefer the non-discriminative; the variables accounting for this difference are not yet clear. The economic concepts related to demand curves have been used to calculate the essential value of different types of reinforcers, so they may be useful to compare the value of the alternatives in the suboptimal choice procedure. The goal of this study was to calculate the essential value of each of the alternatives presented in the suboptimal choice procedure to assess if pigeons (Experiment 1) and rats (Experiment 2) value them differently. In both experiments, the fixed ratio requirement in the initial link was increased throughout sessions in order to obtain the demand curve and calculate the essential value by fitting the exponential-demand model. A Bayesian Linear Mixed-Effects Model indicated that pigeons had higher essential values for the discriminative alternative, whereas rats obtained higher essential values for the non-discriminative alternative. These results suggest that preferences in the suboptimal choice procedure are indeed based on the essential value of the alternatives, and provide a new paradigm to study the variables affecting this phenomenon.

Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: Anested case-control study.

BackgroundInflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery.Methods and findingsOur data come from a case–control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women’s Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m2). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%–97% higher among SGA cases and 33%–39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth.ConclusionsIn this nested case–control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes.

Personality profiles differ between patients with epileptic seizures and patients with psychogenic non-epileptic seizures

PurposePsychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) are often difficult to differentiate, leading to incorrect or delayed diagnosis. The aim of the study was to determine whether patients of these two diagnostic groups possess different personality profiles, and whether they could be used to efficiently screen for PNES in clinical settings. MethodsCollection of data was conducted on 305 patients who completed the NEO-Five Factor Inventory questionnaire during a Video EEG Monitoring admission to the Royal Melbourne Hospital between 2002–2017. Personality differences were investigated using Bayesian linear mixed effects models, with receiver operating characteristic curve analysis computed to evaluate diagnostic accuracy. ResultsThe ‘openness to experience’ domain (BF10 = 21.55, d = −0.43 [95% CI −0.71, −0.17]) and the ‘aesthetic interest’ facet (B10 = 7.98, d= −0.39 [95% CI −0.66, −0.12]) were the only personality factors demonstrating strong evidence for a group difference, with patients with PNES having higher scores compared to the ES group. ES patients had lower scores on these measures compared to the normal population, while PNES patients did not. Both openness to experience and aesthetic interest showed poor sensitivities (53%, 46% respectively) and specificities (69%, 46% respectively) for classifying PNES and ES patients. ConclusionWhile openness and aesthetic interests differ greatly between PNES and ES groups, low sensitivity and specificity suggests their use is limited in a clinical setting. Nevertheless, these findings open up new avenues of research using modern personality models to further understand patients with epilepsy and related presentations.