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Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 – June 2023 compared to the first “wave” of the outbreak in this region, which occurred April – August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in “Wave 2”, cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.

ABSTRACT The objective of the study was to ascertain an optimal Helicobacter pylori diagnostic strategy using population-level laboratory data comparing the performance of serology against urea breath test (UBT). H. pylori diagnostic test results for serology and UBT from two laboratories over a 12-year period (2006–20017) were extracted, linked, and analyzed. A subset of this population underwent both methods of testing within days of each other, enabling a direct comparison of the two methods. The average prevalence of H. pylori positivity was 21.3% by serology and 17.5% by UBT. There were 2,612 individuals who had serology performed first, followed by UBT within 14 days. For this subset, the sensitivity of serology compared with UBT was 96.5% with a specificity of 79.2%. The negative predictive value for serology was 98.4%. Contrary to various recent clinical guidelines, the data show that serology still has utility as a sensitive enough test to be used as an initial H. pylori screening test in a lower prevalence population. Negative serology can be used with confidence to rule out active infection, whereas a positive serology could be followed up with a UBT or a similar performing test such as stool antigen to differentiate active from past infection. For population-based diagnostic recommendations, such a strategy may be ideal since serology generally costs less than UBT and may be combined with a blood draw being done for other diagnostic tests. Continuing to offer serology increases options for patients and may provide economic benefits for single-payer health care systems or health maintenance organizations.IMPORTANCEThis study compares the performance of serology with urea breath test in the diagnosis of Helicobacter pylori in a population-level data set and mimics a head-to-head direct comparison as the study population had both tests performed within 2 weeks of each other. This provides new information supporting the use of serology in a diagnostic algorithm. There are several instances where serology could be preferable to patients to rule out disease, despite some guidelines suggesting serology should not be used.

BackgroundSARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). ObjectiveThis study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. MethodsWe used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. ResultsWe included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. ConclusionsOur study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

Inflammatory responses to acute stimuli are proposed to regulate sleep, but the relationship between chronic inflammation and habitual sleep duration is elusive. Here, we study this relation using genetically predicted level of chronic inflammation, indexed by CRP and IL6 signaling, and self-reported sleep duration. By Mendelian randomization analysis, we show that elevated CRP level within

Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Introduction: Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker. Methods: DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1). Expected Results: Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites. Discussion: The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.

Abstract Introduction Stakeholder engagement remains scarce in basic brain research. However, it can greatly improve the relevance of investigations and accelerate the translation of study findings to policy. The Lifebrain consortium investigated risk and protective factors influencing brain health using cognition, lifestyle and imaging data from European cohorts. Stakeholder activities of Lifebrain—organized in a separate work package—included organizing stakeholder events, investigating public perceptions of brain health and dissemination. Here, we describe the experiences of researchers and stakeholders regarding stakeholder engagement in the Lifebrain project. Methods Stakeholder engagement in Lifebrain was evaluated through surveys among researchers and stakeholders and stakeholders' feedback at stakeholder events through evaluation forms. Survey data were analysed using a simple content analysis approach, and results from evaluation forms were summarized after reviewing the frequency of responses. Results Consortium researchers and stakeholders experienced the engagement activities as meaningful and relevant. Researchers highlighted that it made the research and research processes more visible and contributed to new networks, optimized data collection on brain health perceptions and the production of papers and provided insights into stakeholder views. Stakeholders found research activities conducted in the stakeholder engagement work package to be within their field of interest and research results relevant to their work. Researchers identified barriers to stakeholder engagement, including lack of time, difficulties in identifying relevant stakeholders, and challenges in communicating complex scientific issues in lay language and maintaining relationships with stakeholders over time. Stakeholders identified barriers such as lack of budget, limited resources in their organization, time constraints and insufficient communication between researchers and stakeholders. Conclusion Stakeholder engagement in basic brain research can greatly benefit researchers and stakeholders alike. Its success is conditional on dedicated human and financial resources, clear communication, transparent mutual expectations and clear roles and responsibilities. Public Contribution Patient organizations, research networks, policymakers and members of the general public were involved in engagement and research activities throughout the project duration.

Abstract Circulating levels of the astrocytic marker S100B have been associated with risk of neuropsychiatric or neurological disorders. However, reported effects have been inconsistent, and no causal relations have yet been established. We applied two-sample Mendelian Randomization (MR) on the association statistics from genome-wide association studies (GWAS) for circulating S100B levels measured 5-7 days after birth (the iPSYCH sample) and in an older adult sample (mean age, 72.5 years; the Lothian sample), upon those derived from major depression disorder (MDD), schizophrenia (SCZ), bipolar disorder (BIP), autism spectral disorder (ASD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). We studied the causal relations in the two S100B datasets for risk of these six neuropsychiatric disorders. MR suggested increased S100B levels 5-7 days after birth to causally increase the risk of MDD (OR = 1.014; 95%CI = 1.007–1.022; FDR-corrected p = 6.43×10−4). In older adults, MR suggested increased S100B levels to have a causal relation to the risk of BIP (OR = 1.075; 95%CI = 1.026–1.127; FDR-corrected p = 1.35×10−2). No significant causal relations were found for the other five disorders. We did not observe any evidence for reverse causality of these neuropsychiatric or neurological disorders on altered S100B levels. Sensitivity analyses using more stringent SNP-selection criteria and three alternative MR models suggested the results are robust. Altogether, our findings imply a small cause-effect relation for the previously reported associations of S100B and mood disorders. Such findings may provide a novel avenue for the diagnosis and management of disorders.

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors.

Memory performance results from plasticity, the ability to change with experience. We show that benefit from practice over a few trials, learning slope, is predictive of long-term recall and hippocampal volume across a broad age range and a long period of time, relates to memory training benefit, and is heritable. First, in a healthy lifespan sample (n = 1825, age 4-93 years), comprising 3483 occasions of combined magnetic resonance imaging (MRI) scans and memory tests over a period of up to 11 years, learning slope across 5 trials was uniquely related to performance on a delayed free recall test, as well as hippocampal volume, independent from first trial memory or total memory performance across the five learning trials. Second, learning slope was predictive of benefit from memory training across ten weeks in an experimental subsample of adults (n = 155). Finally, in an independent sample of male twins (n = 1240, age 51-50 years), learning slope showed significant heritability. Within-session learning slope may be a useful marker beyond performance per se, being heritable and having unique predictive value for long-term memory function, hippocampal volume and training benefit across the human lifespan.

Solar cells play an increasing role in global electricity production, and it is critical to maximize their conversion efficiency to ensure the highest possible production. The number of photons entering the absorbing layer of the solar cell plays an important role in achieving a high conversion efficiency. Metal nanoparticles supporting localized surface plasmon resonances (LSPRs) have for years been suggested for increasing light in-coupling for solar cell applications. However, most studies have focused on materials exhibiting strong LSPRs, which often come with the drawback of considerable light absorption within the solar spectrum, limiting their applications and widespread use. Recently, aluminum (Al) nanoparticles have gained increasing interest due to their tuneable LSPRs in the ultraviolet and visible regions of the spectrum. In this study, we present an ideal configuration for maximizing light in-coupling into a standard textured crystalline silicon (c-Si) solar cell by determining the optimal Al nanoparticle and anti-reflection coating (ARC) parameters. The best-case parameters increase the number of photons absorbed by up to 3.3%. We give a complete description of the dominating light–matter interaction mechanisms leading to the enhancement and reveal that the increase is due to the nanoparticles optically exhibiting both particle- and thin-film characteristics, which has not been demonstrated in earlier works.

The human cerebral cortex is highly regionalized, and this feature emerges from morphometric gradients in the cerebral vesicles during embryonic development. We tested if this principle of regionalization could be traced from the embryonic development to the human life span. Data-driven fuzzy clustering was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) (n = 301, 4-12 years). The principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the major embryonic morphometric anterior-posterior (AP) gradient. Embryonic factors showing a clear AP gradient were identified, and we found significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT clusters showed distinguishable life span trajectories in a larger longitudinal dataset (4-88 years, 1633 observations), and the SA and CT clusters showed differential relationships to cognitive functions. This means that regions that developed together in childhood also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample. In conclusion, the development of cortical regionalization is a continuous process from the embryonic stage throughout life.

Abstract Higher general cognitive ability (GCA) is associated with lower risk of neurodegenerative disorders, but neural mechanisms are unknown. GCA could be associated with more cortical tissue, from young age, i.e. brain reserve, or less cortical atrophy in adulthood, i.e. brain maintenance. Controlling for education, we investigated the relative association of GCA with reserve and maintenance of cortical volume, -area and -thickness through the adult lifespan, using multiple longitudinal cognitively healthy brain imaging cohorts (n = 3327, 7002 MRI scans, baseline age 20–88 years, followed-up for up to 11 years). There were widespread positive relationships between GCA and cortical characteristics (level-level associations). In select regions, higher baseline GCA was associated with less atrophy over time (level-change associations). Relationships remained when controlling for polygenic scores for both GCA and education. Our findings suggest that higher GCA is associated with cortical volumes by both brain reserve and -maintenance mechanisms through the adult lifespan.

Cortical asymmetry is a ubiquitous feature of brain organization that is subtly altered in some neurodevelopmental disorders, yet we lack knowledge of how its development proceeds across life in health. Achieving consensus on the precise cortical asymmetries in humans is necessary to uncover the developmental timing of asymmetry and the extent to which it arises through genetic and later influences in childhood. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in seven datasets and chart asymmetry trajectories longitudinally across life (4–89 years; observations = 3937; 70% longitudinal). We find replicable asymmetry interrelationships, heritability maps, and test asymmetry associations in large–scale data. Cortical asymmetry was robust across datasets. Whereas areal asymmetry is predominantly stable across life, thickness asymmetry grows in childhood and peaks in early adulthood. Areal asymmetry is low-moderately heritable (max h2SNP ~19%) and correlates phenotypically and genetically in specific regions, indicating coordinated development of asymmetries partly through genes. In contrast, thickness asymmetry is globally interrelated across the cortex in a pattern suggesting highly left-lateralized individuals tend towards left-lateralization also in population-level right-asymmetric regions (and vice versa), and exhibits low or absent heritability. We find less areal asymmetry in the most consistently lateralized region in humans associates with subtly lower cognitive ability, and confirm small handedness and sex effects. Results suggest areal asymmetry is developmentally stable and arises early in life through genetic but mainly subject-specific stochastic effects, whereas childhood developmental growth shapes thickness asymmetry and may lead to directional variability of global thickness lateralization in the population.

Abstract While immediate effects of memory-training are widely reported in young and older adults, less is known regarding training-dependent hippocampal plasticity across multiple intervention phases, and long-term maintenance of such. Here, 157 healthy young and older adults underwent a training-intervention including two 10 weeks periods of episodic-memory training, separated by two 2 weeks periods of no training. Both age groups showed improvements on a criterion task, which prevailed after 3 years. When compared to the reference condition of no training, relative increases in hippocampal volume were observed after the training across age groups, which were maintained after 10 weeks periods of no training. However, there was age-group dependent temporal variation with respect to timing of effects. Hippocampal volume of the training group did not differ from that of a passive control-group 3 years after the intervention. The young showed an immediate near-transfer effect on a word-association task. We show that training-gains on memory performance can prevail for at least 3 years. Memory training can induce increases in hippocampal volume immediately after the intervention and after months. Episodic-memory training can produce transfer effects to a non-trained memory task in young adults. However, maintained effects on hippocampal volume beyond 10 weeks are uncertain, and likely require continuous training.

Major initiatives attempt to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to, due to its relationship with dementia. Impact of education is difficult to assess, however, because of associations with multiple other factors, requiring large population-representative samples to tease the relationships apart. We studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other important factors. Participants were grouped into five education levels and seven cognitive levels. A total of 1,521 were diagnosed with dementia between ages 60 and 69 y. While having compulsory education only was associated with increased risk (Hazard ratio [HR] = 1.37, CI: 1.17 to 1.60), this association was markedly attenuated when controlling for cognitive test scores (HR = 1.08, CI: 0.91 to 1.28). In contrast, low cognitive score was associated with double risk of later diagnosis, even when controlling for education (HR = 2.00, CI: 1.65 to 2.42). This relationship survived controlling for early-life socioeconomic status and replicated within pairs of brothers. This suggests that genetic and environmental factors shared within families, e.g., common genetics, parental education, socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, nonfamilial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden. [ABSTRACT FROM AUTHOR]

Contemporary accounts of factors that may modify the risk for age-related neurocognitive disorders highlight education and its contribution to a cognitive reserve. By this view, individuals with higher educational attainment should show weaker associations between changes in brain and cognition than individuals with lower educational attainment. We tested this prediction in longitudinal data on hippocampus volume and episodic memory from 708 middle-aged and older individuals using local structural equation modeling. This technique does not require categorization of years of education and does not constrain the shape of relationships, thereby maximizing the chances of revealing an effect of education on the hippocampus-memory association. The results showed that the data were plausible under the assumption that there was no influence of education on the association between change in episodic memory and change in hippocampus volume. Restricting the sample to individuals with elevated genetic risk for dementia (APOE ε4 carriers) did not change these results. We conclude that the influence of education on changes in episodic memory and hippocampus volume is inconsistent with predictions by the cognitive reserve theory.