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Background Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. Methods Children and adolescents aged 6–17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. Results Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. Conclusions Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Patients with schizophrenia have consistently shown brain volumetric abnormalities, implicating both etiological and pathological processes. However, the genetic relationship between schizophrenia and brain volumetric abnormalities remains poorly understood. Here, we applied novel statistical genetic approaches (MiXeR and conjunctional false discovery rate analysis) to investigate genetic overlap with mixed effect directions using independent genome-wide association studies of schizophrenia (n = 130,644) and brain volumetric phenotypes, including subcortical brain and intracranial volumes (n = 33,735). We found brain volumetric phenotypes share substantial genetic variants (74–96%) with schizophrenia, and observed 107 distinct shared loci with sign consistency in independent samples. Genes mapped by shared loci revealed (1) significant enrichment in neurodevelopmental biological processes, (2) three co-expression clusters with peak expression at the prenatal stage, and (3) genetically imputed thalamic expression of CRHR1 and ARL17A was associated with the thalamic volume as early as in childhood. Together, our findings provide evidence of shared genetic architecture between schizophrenia and brain volumetric phenotypes and suggest that altered early neurodevelopmental processes and brain development in childhood may be involved in schizophrenia development. acceptedVersion

ImportancePremenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders.ObjectiveTo assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs).Design, Setting, and ParticipantsWomen from the Norwegian Mother, Father and Child Cohort Study were included in this genetic association study. PRSs were used to determine whether genetic liability for major depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism spectrum disorder were associated with the symptoms of premenstrual disorders, using the PRS for height as a somatic comparator. The sample was recruited across Norway between June 1999 and December 2008, and analyses were performed from July 1 to October 14, 2022.Main Outcomes and MeasuresThe symptoms of premenstrual disorders were assessed at recruitment at week 15 of pregnancy with self-reported severity of depression and irritability before menstruation. Logistic regression was applied to test for the association between the presence of premenstrual disorder symptoms and the PRSs for major psychiatric disorders.ResultsThe mean (SD) age of 56 725 women included in the study was 29.0 (4.6) years. Premenstrual disorder symptoms were present in 12 316 of 56 725 participants (21.7%). The symptoms of premenstrual disorders were associated with the PRSs for major depression (β = 0.13; 95% CI, 0.11-0.15; P = 1.21 × 10−36), bipolar disorder (β = 0.07; 95% CI, 0.05-0.09; P = 1.74 × 10−11), attention deficit/hyperactivity disorder (β = 0.07; 95% CI, 0.04-0.09; P = 1.58 × 10−9), schizophrenia (β = 0.11; 95% CI, 0.09-0.13; P = 7.61 × 10−25), and autism spectrum disorder (β = 0.03; 95% CI, 0.01-0.05; P = .02) but not with the PRS for height. The findings were confirmed in a subsample of women without a history of psychiatric diagnosis.ConclusionsThe results of this genetic association study show that genetic liability for both affective spectrum disorder and major psychiatric disorders was associated with symptoms of premenstrual disorders, indicating that premenstrual disorders have overlapping genetic foundations with major psychiatric disorders.

Low vitamin D (vitD) levels have been consistently reported in schizophrenia (SCZ) suggesting a role in the etiopathology. However, little is known about the role of underlying shared genetic mechanisms. We applied a conditional/conjunctional false discovery rate approach (FDR) on large, nonoverlapping genome-wide association studies for SCZ (N cases = 53 386, N controls = 77 258) and vitD serum concentration (N = 417 580) to evaluate shared common genetic variants. The identified genomic loci were characterized using functional analyses and biological repositories. We observed cross-trait SNP enrichment in SCZ conditioned on vitD and vice versa, demonstrating shared genetic architecture. Applying the conjunctional FDR approach, we identified 72 loci jointly associated with SCZ and vitD at conjunctional FDR

Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features. We analysed genome-wide association study data for all epilepsies (n = 44 889), genetic generalized epilepsy (n = 33 446), focal epilepsy (n = 39 348), schizophrenia (n = 77 096), bipolar disorder (n = 406 405), depression (n = 500 199), attention deficit hyperactivity disorder (n = 53 293) and autism spectrum disorder (n = 46 350). First, we applied the MiXeR tool to estimate the total number of causal variants influencing the disorders. Next, we used the conjunctional false discovery rate statistical framework to improve power to discover shared genomic loci. Additionally, we assessed the validity of the findings in independent cohorts, and functionally characterized the identified loci. The epilepsy phenotypes were considerably less polygenic (1.0 K to 3.4 K causal variants) than the psychiatric disorders (5.6 K to 13.9 K causal variants), with focal epilepsy being the least polygenic (1.0 K variants), and depression having the highest polygenicity (13.9 K variants). We observed cross-trait genetic enrichment between genetic generalized epilepsy and all psychiatric disorders and between all epilepsies and schizophrenia and depression. Using conjunctional false discovery rate analysis, we identified 40 distinct loci jointly associated with epilepsies and psychiatric disorders at conjunctional false discovery rate The extensive genetic overlap with mixed effect directions between psychiatric disorders and common epilepsies demonstrates a complex genetic relationship between these disorders, in line with their bi-directional relationship, and indicates that overlapping genetic risk may contribute to shared pathophysiological and clinical features between epilepsy and psychiatric disorders.

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hemispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.

While genome-wide association studies (GWAS) are increasingly successful in discovering genomic loci associated with complex human traits and disorders, the biological interpretation of these findings remains challenging. We developed the GSA-MiXeR analytical tool for gene-set analysis (GSA), which fits a model for gene-set heritability enrichments for complex traits, accounting for linkage disequilibrium across variants, and allowing the quantification of partitioned heritability and fold enrichment for small gene-sets. We validate the method using extensive simulations and sensitivity analyses. When applied to height and schizophrenia, GSA-MiXeR implicates gene-sets with greater biological specificity compared to standard GSA approaches, including insulin-like growth factor for height, as well as calcium channel function, GABAergic and dopaminergic signaling for schizophrenia. Such biologically relevant gene-sets, often with less than ten genes, are more likely to provide new insights into the pathobiology of complex diseases and highlight potential drug targets.

Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, SCZ, BD and MD. Next, we characterized the identified shared loci using biological annotation resources. OUD data was obtained from the Million Veteran Program (15,756 cases 99,039 controls). SCZ (53,386 cases 77,258 controls), BD (41,917 cases 371,549 controls) and MD (170,756 cases 329,443 controls) data was provided by the Psychiatric Genomics Consortium. We discovered genetic enrichment for OUD conditional on associations with SCZ, BD, MD and vice versa, indicating polygenic overlap with identification of 14 novel OUD loci at condFDRDRD2 on chromosome 11 (BD and MD), at FURIN on chromosome 15 (SCZ, BD and MD), and at the major histocompatibility complex region (SCZ and MD). Our findings provide new insights into the shared genetic architecture between OUD and SCZ, BD, and MD, indicating a complex genetic relationship, suggesting overlapping neurobiological pathways.

MotivationGenome-wide association studies (GWAS) have been successful in identifying genetic variants associated with a particular phenotype. However, many complex phenotypes are influenced by multiple genetic variants with small effects. Detecting the genetic pleiotropy can provide insights into biological mechanisms influencing complex human phenotypes. The recently developed Multivariate Omnibus Statistical Test (MOSTest) has proven to be efficient and powerful, suited for complex large-scale data. The method substantially increased discovery of genetic variants associated with brain MRI phenotypes in the UK Biobank compared to conventionally use multivariate approach. Here we extend the MOSTest to meta-analysis (Meta-MOSTest), facilitating data analysis of multiple phenotypes across multiple cohorts. We evaluated our updated approach in the UK Biobank using brain MRI phenotypes, by comparing the discovery yield of the single-cohort MOSTest versus Meta-MOSTest through simulating sub-cohorts of different sample sizes from 265 to 26501 subjects.ResultsOur method works efficiently on large-scale cohorts with a large number of MRI phenotypes. We found that lower per-cohort sample sizes resulted in a reduced discovery yield indicating a loss of statistical power. However, with a minimum sample size of 250 subjects across cohorts, Meta-MOSTest was equivalent to MOSTest on discovery yield while maintaining a well-calibrated type I error and equivalent statistical power. We conclude that Meta-MOSTest is a useful tool for multivariate analysis across separate brain imaging genetics cohorts.Availability and implementationAll codes are freely available on GitHub: MOSTest and Meta-MOSTest.

The genetic architecture of testosterone is highly distinct between sexes. Moreover, obesity is associated with higher testosterone in females but lower testosterone in males. Here, we ask whether male-specific testosterone variants are associated with a male pattern of obesity and type 2 diabetes (T2D) in females, and vice versa. In the UK Biobank, we conducted sex-specific genome-wide association studies and computed polygenic scores for total (PGSTT) and bioavailable testosterone (PGSBT). We tested sex-congruent and sex-incongruent associations between sex-specific PGSTs and metabolic traits, as well as T2D diagnosis. Female-specific PGSBT was associated with an elevated cardiometabolic risk and probability of T2D, in both sexes. Male-specific PGSTT was associated with traits conferring a lower cardiometabolic risk and probability of T2D, in both sexes. We demonstrate the value in considering polygenic testosterone as sex-related continuous traits, in each sex.

Personality and cognition are heritable mental traits, and their genetic determinants may be distributed across interconnected brain functions. However, previous studies have employed univariate approaches which reduce complex traits to summary measures. We applied the “pleiotropy-informed” multivariate omnibus statistical test (MOSTest) to genome-wide association studies (GWAS) of 35 item and task-level measures of neuroticism and cognition from the UK Biobank (n=336,993). We identified 431 significant genetic loci and found evidence of abundant pleiotropy across personality and cognitive domains. Functional characterisation implicated genes with significant tissue-specific expression in all tested brain tissues and enriched in brain-specific gene-sets. We conditioned independent GWAS of the Big 5 personality traits and cognition on our multivariate findings, which boosted genetic discovery in other personality traits and improved polygenic prediction. These findings advance our understanding of the polygenic architecture of complex mental traits, indicating a prominence of pleiotropic genetic effects across higher-order domains of mental function.Graphical abstract

The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discovered 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% were validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during development were found to significantly impact the measured variations in tissue-specific imaging features. Our results shed new light on the biological determinants of brain tissue composition and their potential overlap with the genetic basis of neuropsychiatric disorders.

Adolescence is a period of brain maturation that may involve a second wave of organizational effects of sex steroids on the brain. Rodent studies suggest that, overall, organizational effects of gonadal steroid hormones decrease from the prenatal/perinatal period to adulthood. Here we used multimodal magnetic resonance imaging to investigate whether 1) testosterone exposure during adolescence (9-17 years) correlates with the structure of cerebral cortex in young men (n = 216, 19 years of age); 2) this relationship is modulated by the timing of testosterone surge during puberty. Our results showed that pubertal testosterone correlates with structural properties of the cerebral cortex, as captured by principal component analysis of T1 and T2 relaxation times, myelin water fraction, magnetization transfer ratio, fractional anisotropy and mean diffusivity. Many of the correlations between pubertal testosterone and the cortical structure were stronger in individuals with earlier (vs. later) testosterone surge. We also demonstrated that the strength of the relationship between pubertal testosterone and cortical structure across the cerebral cortex varies as a function of inter-regional profiles of gene expression specific to dendrites, axonal cytoskeleton, and myelin. This finding suggests that the cellular substrate underlying the relationships between pubertal testosterone and cerebral cortex involves both dendritic arbor and axon.

Through dynamic transactional processes between genetic and environmental factors, childhood and adolescence involve reorganization and optimization of the cerebral cortex. The cortex and its development plays a crucial role for prototypical human cognitive abilities. At the same time, many common mental disorders appear during these critical phases of neurodevelopment. Magnetic resonance imaging (MRI) can indirectly capture several multifaceted changes of cortical macro- and microstructure, of high relevance to further our understanding of the neural foundation of cognition and mental health. Great progress has been made recently in mapping the typical development of cortical morphology. Moreover, newer less explored MRI signal intensity and specialized quantitative T2 measures have been applied to assess microstructural cortical development. We review recent findings of typical postnatal macro- and microstructural development of the cerebral cortex from early childhood to young adulthood. We cover studies of cortical volume, thickness, area, gyrification, T1-weighted (T1w) tissue contrasts such a grey/white matter contrast, T1w/T2w ratio, magnetization transfer and myelin water fraction. Finally, we integrate imaging studies with cortical gene expression findings to further our understanding of the underlying neurobiology of the developmental changes, bridging the gap between ex vivo histological- and in vivo MRI studies.

Importance Many psychiatric disorders can be conceptualized as disorders of brain maturation during childhood and adolescence. Discovering the neurobiological underpinnings of brain maturation may elucidate molecular pathways of vulnerability and resilience to such disorders. Objective To investigate the underlying neurobiological mechanisms of age-associated cortical thinning during maturation and their implications for psychiatric disorders. Design, Setting, and Participants This multicohort analysis used data from 3 community-based studies. The Saguenay Youth Study provided data from 1024 adolescents who were recruited at a single site in Quebec, Canada. The IMAGEN cohort provided data from 1823 participants who were recruited in 8 European cities. The Brazil High Risk Cohort Study for the Development of Childhood Psychiatric Disorders provided data from 815 participants who were recruited in 2 Brazilian cities. Cortical thickness was estimated from the results of magnetic resonance imaging (MRI) scans, and age-associated cortical thinning was estimated in 34 cortical regions. Gene expression from the Allen Human Brain Atlas was aligned with the same regions. Similarities in the interregional profiles of gene expression and the profiles of age-associated cortical thinning were measured. The involvement of dendrites, dendritic spines, and myelin was tested using 3 gene panels. Enrichment for genes associated with psychiatric disorders was tested among the genes associated with thinning and their coexpression networks. Data analysis was conducted between March and October 2019. Main Outcomes and Measures MRI-derived estimates of age-associated cortical thinning and gene expression in 34 cortical regions. Results A total of 3596 individuals aged 9 to 21 years were included in this study. Of those, 1803 participants (50.1%) were female, and the mean (SD) age was 15.2 (2.6) years. Interregional profiles of age-associated cortical thinning were associated with interregional gradients in the expression of genes associated with dendrites, dendritic spines, and myelin; the variance in thinning explained by the gene panels across different points ranged from 0.45% to 10.55% for the dendrite panel, 0.00% to 9.98% for the spine panel, and 0.19% to 26.39% for the myelin panel. These genes and their coexpression networks were enriched for genes associated with several psychiatric disorders. Conclusions and Relevance In this study, genetic similarity between interregional variation in cortical thinning during maturation and multiple psychiatric disorders suggests overlapping molecular underpinnings. This finding adds to the understanding of the neurodevelopmental mechanisms of psychiatric disorders.

Many traits of the brain and body show marked sex differences, but the distributions of their values overlap substantially between the two sexes. To investigate variations associated with biological sex, beyond binary differences, we create continuous sex scores capturing the inter-individual variability in phenotypes. In an adolescent cohort (n = 1,029; 533 females), we have generated three sex scores based on brain-body traits: 'overall' (48 traits), 'pubertal' (26 traits) and 'non-pubertal' (22 traits). We then conducted sex-stratified multiple linear regressions (adjusting for age) using sex scores to test associations with sex hormones, personality traits and internalizing-externalizing behaviour. Higher sex scores (that is, greater 'femaleness') were associated with lower testosterone in males only, as well as lower extraversion, higher internalizing and lower externalizing in both sexes. The associations with testosterone, internalizing and externalizing were driven by pubertal sex scores, underscoring the importance of adolescence in shaping within-sex individual variability.

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4–97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

Injuries to children caused by falling televisions have become more frequent during the last decade. These injuries can be severe and even fatal and are likely to become even more common in the future as TVs increase in size and become more affordable.To formulate guidelines for the prevention of these injuries, the authors systematically reviewed the literature on injuries related to toppling televisions. The authors searched MEDLINE, PubMed, Embase, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library, and Google Scholar according to the Cochrane guidelines for all studies involving children 0–18 years of age who were injured by toppled TVs. Factors contributing to injury were categorized using Haddon’s Matrix, and the public health approach was used as a framework for developing strategies to prevent these injuries.The vast majority (84%) of the injuries occurred in homes and more than three-fourths were unwitnessed by adult caregivers. The TVs were most commonly large and elevated off the ground. Dressers and other furniture not designed to support TVs were commonly involved in the TV-toppling incident. The case fatality rate varies widely, but almost all deaths reported (96%) were due to brain injuries. Toddlers between the ages of 1 and 3 years most frequently suffer injuries to the head and neck, and they are most likely to suffer severe injuries. Many of these injuries require brain imaging and neurosurgical intervention. Prevention of these injuries will require changes in TV design and legislation as well as increases in public education and awareness. Television-toppling injuries can be easily prevented; however, the rates of injury do not reflect a sufficient level of awareness, nor do they reflect an acceptable effort from an injury prevention perspective.

BackgroundAccumulating evidence suggests that breastfeeding benefits the children’s intelligence. Long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk may explain part of this association. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.Methods and FindingsWe investigated this Gene×Environment interaction in a de novo meta-analysis involving >12,000 individuals in the primary analysis, and >45,000 individuals in a secondary analysis using relaxed inclusion criteria. Our primary analysis used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Using random effects meta-analysis, ever breastfeeding was associated with 0.17 (95% CI: 0.03; 0.32) higher Z scores in IQ, or about 2.1 points. There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e., difference between genetic groups of the difference in IQZ scores comparing ever with never breastfed individuals) of 0.12 (95% CI: −0.19; 0.43) and 0.06 (95% CI: −0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with >5.85 and ConclusionsOur findings do not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, our subgroup analysis raises the possibility that breastfeeding supplies LC-PUFAs requirements for cognitive development (if such threshold exists) if it lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and would improve our understanding on the role of breastfeeding duration in the breastfeeding×FADS2 interaction.

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age.

Introduction: Improvements in stroke patient care have led to increases in stroke survivors. However, these survivors are prone to hospital readmission, a burden for both patients and health system deserving of greater investigation. We hypothesize rates and risk factors for stroke patient readmission are not consistent across age. Thus, our aim was to characterize age related patterns of post stroke readmission including trends in patient and healthcare factors. Methods: Using the Discharge Abstract Database, a collection of hospital discharge records maintained by the Canadian Institute for Health Information, patients aged 18+ discharged with the main diagnosis of stroke/TIA between 2003-2014 were identified. Three age groups (18-44, 45-64, 65+) were determined for comparison of age related trends in stroke readmission. Trends were identified using the Cochran-Armitage and Jonckheere-Terpstra tests for binary and larger categorical events respectively. Kaplan-Meier analysis for 90-day recurrence, Chi-squared and multivariable Cox regression analysis for probability and risk of readmission were also performed. Results: A total of 267,768 patients had at least one stroke admission and were discharged alive. The mean age overall was 72 ±14.34 where 4% were aged 18-44, 23% aged 45-64, and 73% aged 65+. The younger groups were predominantly male and the oldest more female (p Conclusions: Age related differences in stroke readmission is evident. With this information better targeted treatment and prevention strategies can be implemented.

We used four methods to compare the breeding chronologies of Marbled Murrelet at two sites at similar latitudes in British Columbia: Desolation Sound on the mainland, inshore of the Strait of Georgia, and Clayoquot Sound on the west coast of Vancouver Island. At both sites, we estimated breeding chronologies from the timing of (1) nest initiation dates determined by radio-telemetry, (2) the chick feeding period determined from observations of fish-holding adults, (3) hatch dates determined from observations of juveniles on the water, and (4) brood patch scores determined from captured birds. At Desolation Sound, these methods each produced a similar distribution of nesting dates, but at Clayoquot Sound, the distribution of nesting dates of radio-tracked birds were substantially biased towards later nests. Despite these methodological difficulties, we found that Marbled Murrelets at Desolation Sound bred ca. 30 d later than at Clayoquot Sound. Regional differences in breeding chronology of this ma...

Marbled Murrelets ( Brachyramphus marmoratus ) observed at sea usually are in pairs through- out the year. Although it has been assumed that these pairs are mates, this assumption has not been formally examined. Using data from three study sites during the breeding seasons of 1997-2001, we found that 92% of the birds that were paired at capture were of male-female pairs, and that paired females were more likely (73%) to be producing eggs than were single females (8%). Fourteen of fifteen pairs were tracked to a single nest location per pair. No pair members caught at sea were found breeding at separate nest sites. One pair was caught in two successive seasons, suggesting that at least some pairs are long lasting. Notably, pair members breeding

We tested the hypothesis that spatial arrangement and movements of bottlenose dolphins (Tursiops truncatus) are related to the spatial arrangement of their prey. From 65 groups we: (1) classified feeding behavior of dolphins according to spatial arrangement and movements of individuals; (2) assessed spatial arrangement and location of prey from direct observations, numbers of associated seabirds, and echosounder recordings; and (3) related feeding behavior of dolphins to spatial arrangement and location of prey. Four feeding categories were defined from cluster and principal component analyses: (1) moving rapidly with no diving, (2) milling with no diving, (3) diving in several locations, and (4) diving in one location. These feeding categories were related to spatial arrangement and location of prey.

Identifying and managing nesting habitat for the threatened Marbled Murrelet (Brachyramphus marmoratus) is difficult because it nests secretively, high in the canopies of large, old conifers of the Pacific Northwest. In British Columbia, low-level surveying from a helicopter is now a recommended standard method of assessing forested landscapes for key microhabitat features—such as availability of potential platforms and developed moss pads for nests, foliage cover above the nest, and accessibility—that are not distinguishable on air photos, satellite images, or forest cover maps. Using a sample of 111 nest sites and 139 random sites within forests greater than 140 years old and distributed across three study areas in south coastal British Columbia, we confirmed the effectiveness of the aerial survey method for classifying overall habitat quality of murrelet nesting habitat. The minimum map units were 3-ha patches. Overall, 40% of the 111 nest sites were in patches classed as Very High, 36% were in High, 15% were in Moderate, 6% were in Low, and 3% were in Very Low. Our ranking of habitat quality was most strongly influenced by estimates of platform availability and moss development. Using an information-theoretic approach, we identified that the Resource Selection Function scores of nest patches improved as elevation decreased, slope grade increased, and the proportion of emergent and canopy trees with mossy pads increased. We also confirmed that study area location affected the strength of model application. Our findings support the potential utility of the low-level aerial survey method for identifying or confirming Marbled Murrelet nesting habitat for land-management purposes.

We studied habitat selection and breeding success in marked populations of a protected seabird (family Alcidae), the marbled murrelet (Brachyramphus marmoratus), in a relatively intact and a heavily logged old-growth forest landscape in south-western Canada. Murrelets used old-growth fragments either proportionately to their size frequency distribution (intact) or they tended to nest in disproportionately smaller fragments (logged). Multiple regression modelling showed that murrelet distribution could be explained by proximity of nests to landscape features producing biotic and abiotic edge effects. Streams, steeper slopes and lower elevations were selected in both landscapes, probably due to good nesting habitat conditions and easier access to nest sites. In the logged landscape, the murrelets nested closer to recent clearcuts than would be expected. Proximity to the ocean was favoured in the intact area. The models of habitat selection had satisfactory discriminatory ability in both landscapes. Breeding success (probability of nest survival to the middle of the chick rearing period), inferred from nest attendance patterns by radio-tagged parents, was modelled in the logged landscape. Survivorship was greater in areas with recent clearcuts and lower in areas with much regrowth, i.e. it was positively correlated with recent habitat fragmentation. We conclude that marbled murrelets can successfully breed in old-growth forests fragmented by logging.

BackgroundSince the 1994 International Conference on Population and Development, male involvement in reproductive health issues has been advocated as a means to improve maternal and child health outcomes, but to date, health providers have failed to achieve successful male involvement in pregnancy care especially in rural and remote areas where majority of the underserved populations live. In an effort to enhance community participation in maternity care, TBAs were trained and equipped to ensure better care and quick referral. In 1997, after the advent of the World Health Organization’s Safe Motherhood initiative, the enthusiasm turned away from traditional birth attendants (TBAs). However, in many developing countries, and especially in rural areas, TBAs continue to play a significant role. This study explored the interaction between men and TBAs in shaping maternal healthcare in a rural Ugandan context.MethodsThis study employed ethnographic methods including participant observation, which took place in the process of everyday life activities of the respondents within the community; 12 focus group discussions, and 12 in-depth interviews with community members and key informants. Participants in this study were purposively selected to include TBAs, men, opinion leaders like village chairmen, and other key informants who had knowledge about the configuration of maternity services in the community. Data analysis was done inductively through an iterative process in which transcribed data was read to identify themes and codes were assigned to those themes.ResultsContrary to the thinking that TBA services are utilized by women only, we found that men actively seek the services of TBAs and utilize them for their wives’ healthcare within the community. TBAs in turn sensitize men using both cultural and biomedical health knowledge, and become allies with women in influencing men to provide resources needed for maternity care.ConclusionIn this study area, men trust and have confidence in TBAs; closer collaboration with TBAs may provide a suitable platform through which communities can be sensitized and men actively brought on board in promoting maternal health services for women in rural communities.