General Linear Mixed-effects Models Research Articles

Calling to the collective: contact calling rates within groups of disc-winged bats do not vary by kinship or association.

Many group-living animals coordinate social behaviours using contact calls, which can be produced for all group members or targeted at specific individuals. In the disc-winged bat, Thyroptera tricolor, group members use 'inquiry' and 'response' calls to coordinate daily movements into new roosts (furled leaves). Rates of both calls show consistent among-individual variation, but causes of within-individual variation remain unknown. Here, we tested whether disc-winged bats produce more contact calls towards group members with higher kinship or association. In 446 experimental trials, we recorded 139 random within-group pairs of one flying bat (producing inquiry calls for roost searching) and one roosting bat (producing response calls for roost advertising). Using generalized linear mixed-effect models (GLMM), we assessed how response and inquiry calling rates varied by sender, receiver, genetic kinship and co-roosting association rate. Calling rates varied consistently across senders but not by receiver. Response calling was influenced by inquiry calling rates, but neither calling rate was higher when the interacting pair had higher kinship or association. Rather than dyadic calling rates indicating within-group relationships, our findings are consistent with the hypothesis that bats produce contact calls to maintain contact with any or all individuals within a group while collectively searching for a new roost site. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics'.

Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Global patterns of nuclear and mitochondrial genetic diversity in marine fishes.

Genetic diversity is a fundamental component of biodiversity. Examination of global patterns of genetic diversity can help highlight mechanisms underlying species diversity, though a recurring challenge has been that patterns may vary by molecular marker. Here, we compiled 6862 observations of genetic diversity from 492 species of marine fish and tested among hypotheses for diversity gradients: the founder effect hypothesis, the kinetic energy hypothesis, and the productivity-diversity hypothesis. We fit generalized linear mixed effect models (GLMMs) and explored the extent to which various macroecological drivers (latitude, longitude, temperature (SST), and chlorophyll-a concentration) explained variation in genetic diversity. We found that mitochondrial genetic diversity followed geographic gradients similar to those of species diversity, being highest near the Equator, particularly in the Coral Triangle, while nuclear genetic diversity did not follow clear geographic patterns. Despite these differences, all genetic diversity metrics were correlated with chlorophyll-a concentration, while mitochondrial diversity was also positively associated with SST. Our results provide support for the kinetic energy hypothesis, which predicts that elevated mutation rates at higher temperatures increase mitochondrial but not necessarily nuclear diversity, and the productivity-diversity hypothesis, which posits that resource-rich regions support larger populations with greater genetic diversity. Overall, these findings reveal how environmental variables can influence mutation rates and genetic drift in the ocean, caution against using mitochondrial macrogenetic patterns as proxies for whole-genome diversity, and aid in defining global gradients of genetic diversity.

Habitat overlap and interspecific competition between snow leopards and leopards in the Central Himalayas of Nepal

Traditionally, leopards (Panthera pardus) and snow leopards (P. uncia) occupy distinct habitats. This study explored the coexistence of snow leopards and leopards within the Gaurishankar Conservation Area in Lapchi Valley, Nepal. Both leopard species are crucial for ecosystem stability as apex predators. Camera trapping data from 2018 to 2023 confirmed twenty species of wild mammals and two species of domesticated livestock in Lapchi Valley, where snow leopards have strong spatio-temporal overlap (Δ=0.74) with leopards. Snow leopards exhibited distinct temporal patterns before and after the leopards’ arrival in the study area. Generalized Linear Mixed Effect Models (GLMM) revealed seasonal and prey-type associations with leopard presence, highlighting the snow leopards' preference for cold season and wild prey. Leopards, however, did not show a significant seasonal preference. The findings highlight Lapchi Valley's ecological richness as well as the need for comprehensive conservation strategies. The record of spatial and temporal overlap between the leopards and snow leopards provides important insights into the behavioral dynamics of apex predators and the need for targeted biodiversity conservation in the face of changing ecosystems. The study emphasizes the valley's transboundary significance, calling for collaborative efforts between Nepal and China to help promote effective conservation management. Lapchi Valley's isolation, traditional and religious importance, and recent infrastructure developments further impact the conservation challenges.

Consistent efficacy outcomes between phase 2 and phase 3 trialsin Crohn's disease or ulcerative colitis in adults: a meta-analysis.

The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. PROSPERO (CRD42023407947).

Review of methodologies for detecting an observer effect in commercial fisheries data

Observers are deployed on commercial fishing trips to collect representative samples of discard rates. However, fishers may change their fishing habits when an observer is onboard (“observer effect”) or observer programs may over- or under-sample portions of the fleet (“deployment effect”). If the extent of these effects are substantial, observer data will not be representative of unobserved trips, potentially biasing the estimation of discards. This sampling bias can impact catch monitoring, stock assessments, and fishery management. The purpose of this study was to examine the power and error rate of several published methods for detecting an observer effect using a simulation of observer and deployment effects at varying sampling ratios (i.e., observer coverage) for several sample statistics. The simplest methods (t-test and F-test for difference of means and variances) provided an accurate although imprecise estimate of the observer effect size, but only when there were no deployment effects. A generalized linear mixed effects model (GLMM) was also not reliable for detecting small bias, but was not confounded by deployment effects and was relatively robust to changing coverage rates. The most complicated tests involved comparing differences in trip characteristics between subsequent trips for observed-unobserved and unobserved-unobserved pairs. These tests were able to detect smaller observer effects and were not confounded by deployment effects, but were unreliable at high coverage rates (>60%), producing both high false positive and false negative rates. Sensitivity tests also showed differing detection accuracy as the distribution of the metric of interest changed. Thus, the optimal test for detecting an observer effect will depend on the metric of interest, the coverage rate, and whether a deployment effect exists. An example from the New England groundfish fishery is provided to illustrate how conflicting results may be explained. Results should always be considered carefully when declaring that an observer effect is or is not occurring because of the sensitivity of the tests.

Physicochemical variables influencing the abundance of Atlantic goliath grouper juveniles (Epinephelus itajara) in a tropical Brazilian mangrove habitat

The purpose of this study was to investigate the relationships between the abundance and occurrence of juvenile Atlantic goliath grouper and physicochemical variables in a tropical mangrove ecosystem, employing a non-lethal methodology. Juvenile Atlantic goliath grouper individuals were captured biweekly, using blue crab traps, across three locations within the São Mateus estuary (18°36′S, 39°44′W), from August 2021 to July 2022. Simultaneously, the physicochemical water variables were assessed during each trap inspection. The physicochemical water variables influence on the abundance and occurrence of Atlantic goliath grouper juveniles were assessed using the Zero-Inflated Binomial (ZIB) and the Poisson (ZIP) generalized linear mixed-effects models (GLMMs). A total of 66 Atlantic goliath grouper juveniles were sampled (Pontal do Sul = 50, Lagoa Creek = 13, and Pitangueiras Creek = 3), ranging from 32 to 319 mm in total length. The best model fitted to presence-absence data (AIC = 278.6) consisted of location, depth, and salinity, with only location having a significant influence on the likelihood of species occurrence. Regarding abundance data, the best model (AIC = 336.4) included location, depth, and turbidity, with only location and depth showing a significant impact on abundance variation, with lower abundance at deeper areas. Although our results indicate a weak significant influence of physicochemical variables on juvenile Atlantic goliath grouper distribution, it is imperative to continue this monitoring effort, considering that additional data may be required to gain a deeper understanding of these patterns.

A price on their heads? Assessing foreign demand as a driver of hornbill hunting in Cameroon

Unsustainable hunting to supply wildlife markets is a global threat to bird species and a key driver of biodiversity declines across Africa. Despite well-documented negative impacts of wildlife trade on many bird species, such as Asian hornbills and African vultures, its consequences for African hornbills remain poorly understood. Here, we use data from both online trade and interviews with hunters in Cameroon to investigate the implications of foreign demand for African hornbills, using a twofold approach. First, we explored factors associated with the prices of hornbill skulls, the most heavily traded and expensive hornbill products, in online markets. Second, we examined the relationship between hunting pressure and market demand using semi-structured interviews with hornbill hunters and traders in Cameroon. In our online sales analysis, we considered factors including numbers of sales, species conservation status, Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) listing, body size, sex, and skull length (including bill and casque). In addition, we considered the number of sound recordings available for focal species, as this factor is highly correlated with species range size and may serve as a proxy for detectability in the field. We then used generalized linear mixed-effects models (GLMM) to identify variables closely associated with the prices of hornbill skulls online. Generalized linear models (GLM) were used to examine the relationship between hunting pressure and the local and foreign demands in Cameroon. We found that online trade included skulls and other products from 20 African and five Asian hornbill species, the latter of which were all CITES-listed. The median online price for a hornbill skull was £117. Nearly half (nine out of 20) of the African hornbill species found in online trade were native to Cameroon. The three most heavily traded species—Yellow-casqued Hornbill (Ceratogymna elata), Black-casqued Hornbill (C. atrata), and White-thighed Hornbill (Bycanistes albotibialis)—accounted for 66% of online hornbill products. Larger-bodied hornbill species classified as threatened, subject to CITES regulations, and species with higher numbers of sound recordings available tended to command higher prices online and thus likely face higher hunting pressure. We also found that foreign demand has a significant impact on hornbill hunting pressure, particularly among younger hunters. Approximately 73% of Cameroonian hunters interviewed targeted hornbills, with 91% of these motivated to acquire hornbill heads for trade, and 98% intending to sell their products to foreign buyers. Our findings highlight the urgent need to address the negative impacts of international wildlife trade and implement measures to protect African hornbill populations from increasing threats of overexploitation.

Functional reorganization of memory processing in the hippocampus is associated with neuroprotector GLP-1 levels in type 2 diabetes

Type 2 diabetes (T2D) often impairs memory functions, suggesting specific vulnerability of the hippocampus. In vivo neuroimaging studies relating encoding and retrieval of memory information with endogenous neuroprotection are lacking. The neuroprotector glucagon-like peptide (GLP-1) has a high receptor density in anterior/ventral hippocampus, as shown by animal models. Using an innovative event-related fMRI design in 34 participants we investigated patterns of hippocampal activity in T2D (n = 17) without mild cognitive impairment (MCI) versus healthy controls (n = 17) during an episodic memory task. We directly measured neurovascular coupling by estimating the hemodynamic response function using event-related analysis related to encoding and retrieval of episodic information in the hippocampus. We applied a mixed-effects general linear model analysis and a two-factor ANOVA to test for group differences. Significant between-group differences were found for memory encoding, showing evidence for functional reorganization: T2D patients showed an augmented activation in the posterior hippocampus while anterior activation was reduced. The latter was negatively correlated with both GLP-1 pre- and post-breakfast levels, in the absence of grey matter changes. These results suggest that patients with T2D without MCI have pre-symptomatic functional reorganization in brain regions underlying episodic memory, as a function of the concentration of the neuroprotective neuropeptide GLP-1.

Flexible multi-step hypothesis testing of human ECoG data using cluster-based permutation tests with GLMEs

BackgroundTime series analysis is critical for understanding brain signals and their relationship to behavior and cognition. Cluster-based permutation tests (CBPT) are commonly used to analyze a variety of electrophysiological signals including EEG, MEG, ECoG, and sEEG data without a priori assumptions about specific temporal effects. However, two major limitations of CBPT include the inability to directly analyze experiments with multiple fixed effects and the inability to account for random effects (e.g. variability across subjects). Here, we propose a flexible multi-step hypothesis testing strategy using CBPT with Linear Mixed Effects Models (LMEs) and Generalized Linear Mixed Effects Models (GLMEs) that can be applied to a wide range of experimental designs and data types. MethodsWe first evaluate the statistical robustness of LMEs and GLMEs using simulated data distributions. Second, we apply a multi-step hypothesis testing strategy to analyze ERPs and broadband power signals extracted from human ECoG recordings collected during a simple image viewing experiment with image category and novelty as fixed effects. Third, we assess the statistical power differences between analyzing signals with CBPT using LMEs compared to CBPT using separate t-tests run on each fixed effect through simulations that emulate broadband power signals. Finally, we apply CBPT using GLMEs to high-gamma burst data to demonstrate the extension of the proposed method to the analysis of nonlinear data. ResultsFirst, we found that LMEs and GLMEs are robust statistical models. In simple simulations LMEs produced highly congruent results with other appropriately applied linear statistical models, but LMEs outperformed many linear statistical models in the analysis of “suboptimal” data and maintained power better than analyzing individual fixed effects with separate t-tests. GLMEs also performed similarly to other nonlinear statistical models. Second, in real world human ECoG data, LMEs performed at least as well as separate t-tests when applied to predefined time windows or when used in conjunction with CBPT. Additionally, fixed effects time courses extracted with CBPT using LMEs from group-level models of pseudo-populations replicated latency effects found in individual category-selective channels. Third, analysis of simulated broadband power signals demonstrated that CBPT using LMEs was superior to CBPT using separate t-tests in identifying time windows with significant fixed effects especially for small effect sizes. Lastly, the analysis of high-gamma burst data using CBPT with GLMEs produced results consistent with CBPT using LMEs applied to broadband power data. ConclusionsWe propose a general approach for statistical analysis of electrophysiological data using CBPT in conjunction with LMEs and GLMEs. We demonstrate that this method is robust for experiments with multiple fixed effects and applicable to the analysis of linear and nonlinear data. Our methodology maximizes the statistical power available in a dataset across multiple experimental variables while accounting for hierarchical random effects and controlling FWER across fixed effects. This approach substantially improves power leading to better reproducibility. Additionally, CBPT using LMEs and GLMEs can be used to analyze individual channels or pseudo-population data for the comparison of functional or anatomical groups of data.

Effects of different land-use planning instruments on urban shrub and tree canopy cover in Zurich, Switzerland

Sustainable urban development requires not only dense and land-saving construction, but also a large share of urban vegetation. A planned unit development (PUD) is a land-use planning instrument that is often used to improve urban quality in urban renewal and densification worldwide. In this study, we analyse the influence of PUDs on urban vegetation in the Canton of Zurich, Switzerland, by contrasting them with conventional zoning. We modelled the share of shrub and tree canopy cover per neighbourhood block using generalized linear mixed effect models (GLMM), with the type of planning instrument as the focal predictor amongst other control variables known from the literature to be influential on urban vegetation. Results show that PUDs are associated with significantly less urban vegetation cover than conventional zoning. This is unexpected and raises concerns. Given how important PUDs are as levers for improving urban quality, their observed inability to promote valuable shrub and tree structures leads us to recommend that good landscape planning and long-term management of (existing and new) urban vegetation be included as an additional standard criterion of high priority in the assessment of future PUDs.

A natural experiment to assess recess frequency on children’s physical activity in Arizona (U.S.) elementary schools

BackgroundIn the United States, the number of state policies mandating recess in schools has rapidly increased over the past decade; however, few policies specify recess frequency. Informed by an ecological model of physical activity (PA) policy, this study examined and compared total amounts and intensity of PA expended during recess among children attending schools in compliance with Arizona recess policy ARS§ 15–118 mandating 2 + daily recess periods versus not.MethodsPA during recess was measured among grade three children (ages 8–10) in four randomly selected elementary schools (two complying averaging 30 daily recess minutes; two non-complying averaging 15 daily recess minutes) in Maricopa County, Arizona. Group-level PA was assessed by direct observation using the System for Observing Play and Leisure (137 observations). A subset of students (N = 134) from all schools wore ActiGraph GT3X + devices during recess to measure individual PA. General linear mixed effects models were used to analyze the impact of recess frequency on group and individual PA during recess.ResultsStudents attending complying schools spent significantly greater proportions of time in moderate-to-vigorous PA (MVPA) based on direct observation (5%) and accelerometry (15%) and less time being sedentary based on accelerometry (14%) during recess. Across the school day, this would equate to 5.1 more MVPA minutes based on systematic direct observation and 9.5 more MVPA minutes based on accelerometry, and 4.1 less minutes being sedentary based on accelerometry if students received two daily 15-minute recess periods compared to one.ConclusionsStudents attending elementary schools implementing 2 + recesses, in accordance with state policy, demonstrated greater MVPA and less sedentary time, providing preliminary evidence that recess frequency is associated with greater PA intensity among children during recess. Schools that adhere to state-level PA policies may provide a more supportive environment for PA, resulting in increased movement among students. Specifying recess frequency should be considered in statewide recess policy.

Effect of digital monitoring and counselling on self-management ability in patients with rheumatoid arthritis: a randomised controlled trial.

To assess a remote physiotherapist (PT) counselling intervention using self-monitoring tools for improving self-management ability, physical activity participation, and health outcomes in people with rheumatoid arthritis (RA). Eligible participants were randomly assigned to receive group education, a Fitbit®, a self-monitoring app, and PT counselling phone calls (Immediate Group). The Delayed Group received a monthly e-newsletter until week 26, and then the intervention. The primary outcome was Patient Activation Measure (PAM-13). Participants were assessed at baseline, 27 weeks (the primary end point) and 53 weeks. Secondary outcomes included disease activity, pain, fatigue, depression, sitting/walking habits, daily physical activity time, and daily awake sedentary time. Generalized Linear Mixed-effect Models (GLMMs) were used to assess the effect of the intervention on the change of each outcome measure from the initiation to 27 weeks after the intervention. Analysis included 131 participants (91.6% women; 80.2% completed during the COVID-19 pandemic). The mean change of PAM-13 at 27 weeks was 4.6 (SD = 14.7) in the Immediate Group vs -1.6 (SD = 12.5) in the Delayed Group. The mean change in Delayed Group at 53 weeks (after the 26-week intervention) was 3.6 (SD = 14.6). Overall, the intervention improved PAM-13 at 27 weeks post-intervention from the GLMM analysis (adjusted coefficient: 5.3; 95% CI: 2.0, 8.7; p = <0.001). Favourable intervention effects were also found in disease activity, fatigue, depression, and self-reported walking habit. Remote counselling paired with self-monitoring tools improved self-management ability in people with RA. Findings of secondary outcomes indicate that the intervention had a positive effect on symptom management.

Effect of grazing and climatic factors on biodiversity-ecosystem functioning relationships in grassland ecosystems -a case study of typical steppe in Inner Mongolia, China.

Biodiversity underpins grassland ecological functions and productive capacities. By studying the mechanisms for the maintenance of species diversity in animal communities, we can provide important theoretical guidance for the optimization of grazing management and biodiversity protection. The typical grassland of Xilingol in Inner Mongolia, China, was used as the experimental area, and a grazing intensity experiment was set up. This consisted of four gradient levels that were grazed by sheep, which were available for continuous monitoring, namely control standard sheep unit·day·hectare-1·year-1 (CK, 0 SSU·d·hm-2y-1), light grazing (LG, 170 SSU·d·hm-2·y-1), moderate grazing (MG, 340 SSU·d·hm-2·y-1), and high grazing (HG, 510 SSU·d·hm-2·y-1). Nine consecutive years of multi-indicator monitoring of vegetation was carried out from 2014-2022, using monitoring data coupled with time series and inter-annual climatic (relative moisture index, RMI) fluctuations. This was done to analyze the impacts of disturbances, such as grazing use and climatic fluctuations, on the diversity of species and above-ground productivity of the community, thereby exploring the relationship between diversity and productivity, and provide possible explanations for the emergence of a range of ecological responses. The statistical analysis methods used were One-way Analysis of Variance (ANOVA), general linear regression and mixed-effects models. The main conclusions of this study are as follows: (1) The grassland in the experimental area under CK had the highest diversity and productivity and the ecosystem was better able to buffer the negative impacts of climatic drought. Furthermore, the effect of climate on productivity and diversity weakened as the intensity of grazing increased. (2) LG to MG had a constant diversity. (3) Grazing utilization changed the relationship between community species diversity and aboveground productivity by releasing spatial community resources, altering the structure of plant communities, weakening competitive exclusion, and strengthening complementary effects. However, under all of the conditions there is a brief stage in the time series when diversity is stimulated to increase, and the higher the grazing intensity, the earlier this occurs.

Course of objectively measured physical activity and sleep in postmenopausal breast cancer survivors during the COVID-19 pandemic: A 1-year follow-up.

As physical inactivity and poor sleep quality may impose additional risk for cancer recurrence and overall mortality in postmenopausal breast cancer (PMBC) survivors, it is important to gain insight into the effect of the COVID-19 pandemic on their physical activity (PA) and sleep level. This study aimed to assess the course of their physical activity (PA) and sleep throughout governmental measures against COVID-19 during 12 months of the COVID-19 pandemic. PMBC survivors (n = 96) wore an ActiGraph wGT3X-BT for seven consecutive days at 12 and 18 months after diagnosis and additional measurements were taken after onset of the second (partial) COVID-19 lockdown. Longitudinal data was categorized into four timepoints: before onset of COVID-19 (T1), during the initial lockdown (T2), in between initial and second lockdown (T3), and during the second lockdown (T4). General linear mixed effects models assessed differences in moderate-to-vigorous physical activity (MVPA) per day, total minutes of PA per day, average acceleration, intensity gradient, sleep efficiency, and sleep duration over time. Levels of MVPA per day before COVID-19 were low (Median = 20.9min/day (IQR = 10.8;36.2)), and time spent physically active was most often in light intensity, which remained stable throughout the pandemic. Sleep duration (Median = 442.8min/night (IQR = 418.3;478.0)) and efficiency (85.9% (IQR = 79.6;88.4)) was sufficient before COVID-19 and showed stability over time. Low levels of PA with mostly light intensity, and adequate sleep efficiency and duration were observed before COVID in PMBC survivors. This was not further affected by COVID-19 governmental measures.

Molecular hallmarks of Alzheimer’s disease with a multimodal single cell atlas of the cortex

AbstractBackgroundThe Seattle Alzheimer’s Disease Cell Atlas (SEA‐AD, https://sea-ad.org) is a large‐scale effort to identify, at single cell resolution, the cellular and molecular mechanisms that cause AD and facilitate its progression. SEA‐AD brings together quantitative neuropathology (QNP) derived from classic histopathological and cell type stains with single nucleus transcriptomics, epigenetics, and spatial transcriptomics on a cohort of 84 aged donors that span the pathological and cognitive disease spectrum, including unaffected controls.MethodWe ordered SEA‐AD donors based on QNP using a Bayesian latent space model to construct a model‐estimated “pseudo‐progression” (PS). We then used a general linear mixed effects model to test for gene expression changes along the PS in each of the BRAIN initiative’s 139 cell types present in SEA‐AD’s single nucleus RNA sequencing dataset (∼1.2 million nuclei) from the middle temporal gyrus. By separately fitting models to donors with lower and higher pathology, we obtained two beta coefficients for each gene that enabled distinction between early, late, and consistent up‐ and down‐regulation along PS. We then tested whether the betas for each gene were different across all cell types or in only certain ones to measure specificity. We curated gene modules from biological processes potentially relevant to AD, identified in gene‐set enrichment analyses and prior studies, and categorized each gene within them based on their dynamics and specificity.ResultRoughly one‐third of genes had differential expression across neuronal cell types (mean betas &gt; 0.2), split evenly between up‐ and down‐regulation, while a smaller subset were changed in specific cell types. Modules enriched in broadly changed genes that had increased expression early in PS included those involved with the microtubule cytoskeleton, vesicle adaptors, and neurotransmitter receptors, while those with decreased expression included those involved with cholesterol synthesis, glycolysis, mitochondrial function, and neurofilaments. Among the genes changed only in specific cell types were NOTCH2 in Somatostatin and Parvalbumin interneurons selectively vulnerable to pathology, PTPRG in disease associated microglia, and COL21A1 in disease associated astrocytes.ConclusionBroadly affected modules identified by SEA‐AD suggest most neurons are affected by disease pathology and cell type‐specific differences may provide clues to selective vulnerability.

Antimicrobial resistance of Escherichia coli in the UK: comparison of single vs. pooled samples from healthy pigs.

This study compared the antimicrobial resistance (AMR) of Escherichia coli detected from single samples vs. pooled samples at herd level. The national monitoring dataset included isolates from one sample per pig holding, whereas the research study included isolates from pooled samples of 10 pigs per holding. In both datasets, caecal samples were collected from healthy pigs randomly selected at slaughterhouses and plated on non-selective and antibiotic selective media. Resistance against a panel of nine antibiotics was compared between datasets by generalized linear mixed effects models (GLMMs) and by bootstrapped generalized linear model (GLM) to account for pooling. The highest proportion of resistant E. coli was observed against tetracycline and ampicillin in both datasets. In non-selective media, single and pooled samples showed similar results, but the bootstrapped GLM detected significantly lower resistance to ciprofloxacin and nalidixic acid in the national dataset. In selective media, a significantly greater proportion of resistant isolates was observed in the research dataset for ceftazidime (OR: 0.05, 95%CI=0.01-0.42) and nalidixic acid (OR: 0.15, 95%CI=0.05-0.51). The results suggest that one sample per holding provides similar information on AMR at herd level as pooled samples for most of the tested antibiotics, although less resistance to ciprofloxacin, ceftazidime, and nalidixic acid was detected.

Characterization of spatiotemporal dynamics of binary and graded tonic pain in humans using intracranial recordings.

Pain is a complex experience involving sensory, emotional, and cognitive aspects, and multiple networks manage its processing in the brain. Examining how pain transforms into a behavioral response can shed light on the networks' relationships and facilitate interventions to treat chronic pain. However, studies using high spatial and temporal resolution methods to investigate the neural encoding of pain and its psychophysical correlates have been limited. We recorded from intracranial stereo-EEG (sEEG) electrodes implanted in sixteen different brain regions of twenty patients who underwent psychophysical pain testing consisting of a tonic thermal stimulus to the hand. Broadband high-frequency local field potential amplitude (HFA; 70-150 Hz) was isolated to investigate the relationship between the ongoing neural activity and the resulting psychophysical pain evaluations. Two different generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. The first model examined the relationship between HFA and whether the patient responded "yes" or "no" to whether the trial was painful. The second model investigated the relationship between HFA and how painful the stimulus was rated on a visual analog scale. GLMEs revealed that HFA in the inferior temporal gyrus (ITG), superior frontal gyrus (SFG), and superior temporal gyrus (STG) predicted painful responses at stimulus onset. An increase in HFA in the orbitofrontal cortex (OFC), SFG, and striatum predicted pain responses at stimulus offset. Numerous regions, including the anterior cingulate cortex, hippocampus, IFG, MTG, OFC, and striatum, predicted the pain rating at stimulus onset. However, only the amygdala and fusiform gyrus predicted increased pain ratings at stimulus offset. We characterized the spatiotemporal representations of binary and graded painful responses during tonic pain stimuli. Our study provides evidence from intracranial recordings that the neural encoding of psychophysical pain changes over time during a tonic thermal stimulus, with different brain regions being predictive of pain at the beginning and end of the stimulus.

Patterns of reef fish taxonomic and functional diversity in the Eastern Tropical Pacific

A core challenge in ecology is identifying the factors that determine species distribution and functional diversity of species assemblages. Reef fish are the most diverse group of vertebrates, form taxonomically rich and functionally diverse communities and represent a key source of food for humans. We examine regional distribution patterns of reef fish species richness and functional diversity and investigate how these are determined by historical, biogeographic, energetic, and anthropogenic factors. We compiled data from 3,312 underwater visual censuses performed at 122 locations comprising rocky and coral reefs along the Eastern Tropical Pacific (ETP). We used generalized linear mixed‐effects models (GLMMs) implemented in a Bayesian framework to investigate whether distance from quaternary refugia, distance from mainland, shelf area, primary productivity, sea surface temperature (SST), human population gravity, and conservation status influence reef fish species richness and functional diversity in the ETP. Species richness and functional richness (FRic) peaked towards the center of the ETP and our null model suggests that FRic followed a spatial pattern that would be predicted by species richness. Additionally, functional evenness (FEve) was highest at higher latitudes whereas functional dispersion (FDis) was homogeneous throughout the ETP. Species richness was negatively influenced by shelf area and distance from mainland, but positively influenced by SST and conservation status. FEve was influenced by human population gravity and FDis by shelf area. Reef fish species richness and functional diversity in the ETP exhibited a strong division within the region mainly mediated by SST and human population gravity. Our results also suggest that dominant species within small shelf areas share more common traits than dominant species in large areas. This study uncovers previously unknown regional patterns of reef fish functional diversity and provides new insights into how historical, biogeographic, energetic, and anthropogenic factors influence complementary biodiversity facets.

Titi monkey father-daughter bond-related behaviors explain stress response variability

Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds. We established a method for quantifying variability in expression of bond-related behaviors in females (n = 12), and the present study is the second to use this method for explaining titi monkey responses to behavioral tests. We also investigated how manipulations of oxytocin (OT) and vasopressin (AVP) influenced juvenile behavior and physiology. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT receptor antagonist (OTA) prior to an acute social separation. General linear mixed-effects model results revealed fathers were significant behavioral and physiological stress buffers for their daughters, as evidenced by fewer distress vocalizations (p < 0.001), less locomotion (p < 0.001), and lower plasma cortisol (p < 0.001) in a social separation paradigm. Females vocalized less if they exhibited greater expression of bond-related behaviors with their fathers as infants (p = 0.01), and this stress-buffering effect remained even when the daughter was separated from the father (p = 0.001). While treatments did not alter behaviors, OTA treatment caused the largest rise in plasma cortisol (p < 0.001), suggesting blockade of OT receptors can inhibit fathers’ stress-buffering effects. Remarkably, females with greater expression of father-daughter bond-related behaviors exhibited an overall reduced physiological separation distress response (p = 0.04). Findings from the present study advance current knowledge of the neurobiological mechanisms foundational to female bonds and help inform how social disruptions may differently impact individuals based on expression of bond-related behaviors.