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Above the first lactate threshold, the steady‐state V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ is delayed or prevented due to the V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ slow component (V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$). This phenomenon has been associated with muscle fatigue, but evidence for a causal relationship is equivocal. Moreover, little is known about the contribution of pedalling technique adjustments to V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$ during fatiguing cycling exercise. Eleven participants completed constant power trials at 10% above the second lactate threshold. Muscle fatigue was assessed, utilizing femoral nerve stimulation and instrumented pedals, while V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$, quadriceps oxygenation, electromyography (EMG) and pedal force components were measured. Correlations between physiological and mechanical variables were estimated at group and individual levels. Group correlations revealed moderate values for V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$ with quadriceps twitch force (r = −0.51) and muscle oxygenation (r = −0.52), while weak correlations were observed for EMG amplitude (r = 0.26) and EMG mean power frequency (r = −0.16), and with pedalling mechanical variables such as peak total downstroke force (r = −0.16), minimum total upstroke force (r = −0.16) and upstroke index of effectiveness (r = 0.16). The findings here align with prior literature reporting significant correlations between the magnitude of muscle fatigue and that of V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$, although there was large interindividual variability for all the reported correlations. Considering the heterogeneity in the data, it is difficult to determine the relative impact of pedalling technique adjustments on V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$ overall, but the present study opens the possibility that in some cases, increases in V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ secondary to technical adjustments may be 'superimposed' on the underlying V̇O2SC${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{SC}}}}$. What is the central question of this study?Is there an interplay between muscle fatigue and alterations in pedalling technique in the development of the V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ slow component during cycling?What is the main finding and its importance?There was a significant correlation between the V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ slow component and muscle fatigue, although they were not temporally aligned, and substantial individual heterogeneity existed in the strength of the association. Alterations in pedalling technique were shown to be weakly correlated with the V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ slow component across the whole group, but certain individuals showcased strong associations, suggesting that biomechanical changes may play a role in the development of the V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ slow component in some individuals. [ABSTRACT FROM AUTHOR]

Background: First Contact Practitioners (FCP) have developed as a more advanced physiotherapy clinical role delivering specialist MSK services in GP practice settings. They aim to support GPs in effectively managing increasing patient workloads. As FCPs are now a more established NHS role, it is important to understand how these clinicians perceive their roles to guide and support future service development. Aims: To review the current evidence regarding the experience of FCPs in the UK. To understand how FCPs perceive their role. To gain an insight into FCP practice which can inform future primary research studies. Method: A systematic review of FCP primary qualitative research studies. Multiple database and grey literature search with screening following PRISMA guidelines. Qualitative critical appraisal and analysis used tools and frameworks from the Joanna Briggs Institute. Results: The review reports on 11 included studies which informed the creation of six key concepts impacting upon FCP role experience and perceptions. These were complexity, competency and role development, role understanding, job satisfaction, wellbeing and burnout and service delivery. Conclusion: FCP clinicians feel broadly positive about their roles, although they report a clear risk of burnout and associated negative impact on their wellbeing. Job satisfaction is linked to adequate training and developing the competencies required to manage patients in an environment of clinical uncertainty. Having access to regular clinical mentorship is a key requirement and FCPs must adapt to the specific demands of work in a GP practice environment. [ABSTRACT FROM AUTHOR]

Communities across Aotearoa New Zealand are collaborating to reverse ecological decline, but little attention has been given to understanding the deeper relationship required with our physical and socio‐cultural landscapes. We used knowledge co‐production to develop 11 insights to support place‐based strategies that nurture a collective responsibility to revitalise both people and place. Twenty‐five subject matter experts across communities, government, industry and research drew from their collective expertise and the review of 63 local‐to‐global case study examples of farm‐to‐community‐scale place‐based approaches. A key output from this work is an Aotearoa New Zealand framework that diagrammatically represents the interdisciplinary nature of the 11 insights. [ABSTRACT FROM AUTHOR]

Aim: To investigate clinicians' psychosocial experiences navigating interdisciplinary care for children with severe neurological impairment (SNI), for example children with a developmental epileptic encephalopathy; secondarily, to identify preferences for future interventions to support clinicians caring for children with SNI. Method: We conducted a qualitative descriptive study with interdisciplinary clinicians by using a purposeful sampling recruitment strategy. Twenty‐four participants with expertise caring for children with SNI completed in‐depth, semi‐structured interviews. We transcribed the interviews, de‐identified them, and performed inductive thematic analysis. Results: Thematic analysis elicited interrelated themes. Clinicians experienced immense professional barriers providing patient‐centred care across fragmented healthcare contexts. Physical, emotional, and psychological impacts were attributed to inadequate reflective practice training and a paucity of integrated resources to support clinicians over time. Multipronged strategies were prioritized by clinicians, incorporating psychoeducation, interdisciplinary peer mentorship, and psychological resources to build reflective practice skills for clinicians providing complex care in an advancing era of medicine. Interpretation: This study provides novel and in‐depth insight into clinicians' experiences navigating care for children with SNI. The results will be used to inform future integrated and multipronged co‐developed resources tailored for clinicians, on the basis of their recommendations. [ABSTRACT FROM AUTHOR]

Disease outbreaks are one of the key threats to great apes and other wildlife. Because the spread of some pathogens (e.g., respiratory viruses, sexually transmitted diseases, ectoparasites) are mediated by social interactions, there is a growing interest in understanding how social networks predict the chain of pathogen transmission. In this study, we built a party network from wild chimpanzees (Pan troglodytes), and used agent‐based modeling to test: (i) whether individual attributes (sex, age) predict individual centrality (i.e., whether it is more or less socially connected); (ii) whether individual centrality affects an individual's role in the chain of pathogen transmission; and, (iii) whether the basic reproduction number (R0) and infectious period modulate the influence of centrality on pathogen transmission. We show that sex and age predict individual centrality, with older males presenting many (degree centrality) and strong (strength centrality) relationships. As expected, males are more central than females within their network, and their centrality determines their probability of getting infected during simulated outbreaks. We then demonstrate that direct measures of social interaction (strength centrality), as well as eigenvector centrality, strongly predict disease dynamics in the chimpanzee community. Finally, we show that this predictive power depends on the pathogen's R0 and infectious period: individual centrality was most predictive in simulations with the most transmissible pathogens and long‐lasting diseases. These findings highlight the importance of considering animal social networks when investigating disease outbreaks. Summary: Older male Chimpanzees are the most central within their network, and their centrality determines their probability of getting infected during simulated outbreaks.Direct measures of social interaction (strength centrality), as well as eigenvector centrality, strongly predict disease dynamics in the chimpanzee community.This predictive power depends on the pathogen's R0 and infectious period: individual centrality was most predictive in simulations with the most transmissible pathogens and long‐lasting diseases. [ABSTRACT FROM AUTHOR]

Primates show large interindividual variability in the character and quantity of interactions between mothers and their immature offspring. Multiple studies have documented associations between maternal behavior and the occurrence or frequency of certain behaviors among offspring, but it remains unclear whether and how early maternal interactions generally affect behavioral development in offspring. We followed two wild groups of Japanese macaques on Yakushima island and investigated the relationship between maternal behavior and several types of behavior performed by 35 juvenile offspring. We further asked if the impact of maternal behavior on juvenile behavior persists regardless of the distance between mother and offspring, testing whether the influence extends beyond cases when the mother is nearby. We found that juveniles whose mothers frequently rejected them approached and played with others more often, independent of their mother's presence. Juveniles of more protective mothers were in proximity to fewer other individuals and played less, but only if their mothers were nearby. Maternal rejection appears to exert a generalized effect on offspring behavior that endures when mothers are absent. In contrast, effects of maternal protectiveness may be temporary and/or reflect direct maternal influences, such as active intervention in offspring interactions, or effects of the mother's own social relationships on offspring interactions. Our results suggest that understanding how maternal behavior affects offspring development requires paying attention to the context of juvenile behavior, including the mother's distance from her offspring. Research Highlights: Maternal rejection and protectiveness are associated with a decrease in the time juveniles spent in proximity with adults, but only in maternal presence.The more rejective their mother is, the more juveniles approach others regardless of maternal presence, and the more they play when the mother is not around.The more protective their mother is, the more juveniles scratch themselves when she is not around, and the less they play in maternal presence. [ABSTRACT FROM AUTHOR]

Aim: Arctic plants survived the Pleistocene glaciations in unglaciated refugia. The number, ages, and locations of these refugia are often unclear. We use high‐resolution genomic data from present‐day and Little‐Ice‐Age populations of Arctic Bell‐Heather to re‐evaluate the biogeography of this species and determine whether it had multiple independent refugia or a single refugium in Beringia. Location: Circumpolar Arctic and Coastal British Columbia (BC) alpine. Taxon: Cassiope tetragona L., subspecies saximontana and tetragona, outgroup C. mertensiana (Ericaceae). Methods: We built genotyping‐by‐sequencing (GBS) libraries using Cassiope tetragona tissue from 36 Arctic locations, including two ~250‐ to 500‐year‐old populations collected under glacial ice on Ellesmere Island, Canada. We assembled a de novo GBS reference to call variants. Population structure, genetic diversity and demography were inferred from PCA, ADMIXTURE, fastsimcoal2, SplitsTree, and several population genomics statistics. Results: Population structure analyses identified 4–5 clusters that align with geographic locations. Nucleotide diversity was highest in Beringia and decreased eastwards across Canada. Demographic coalescent analyses dated the following splits with Alaska: BC subspecies saximontana (5 mya), Russia (~1.4 mya), Europe (>200–600 kya), and Greenland (~60 kya). Northern Canada populations appear to have formed during the current interglacial (7–9 kya). Admixture analyses show genetic variants from Alaska appear more frequently in present‐day than historic plants on Ellesmere Island. Conclusions: Population and demographic analyses support BC, Alaska, Russia, Europe and Greenland as all having had independent Pleistocene refugia. Northern Canadian populations appear to be founded during the current interglacial with genetic contributions from Alaska, Europe and Greenland. We found evidence, on Ellesmere Island, for continued recent gene flow in the last 250–500 years. These results suggest that a re‐analysis of other Arctic species with shallow population structure using higher resolution genomic markers and demographic analyses may help reveal deeper structure and other circumpolar glacial refugia. [ABSTRACT FROM AUTHOR]

The measurement of skeletal muscle fatigue in response to cycling exercise is commonly done in isometric conditions, potentially limiting its ecological validity, and creating challenges in monitoring the time course of muscle fatigue across an exercise bout. This study aimed to determine if muscle fatigue could be reliably assessed by measuring quadriceps twitch force evoked while pedaling, using instrumented pedals. Nine participants completed three laboratory visits: a step incremental test to determine power output at lactate threshold, and on separate occasions, two constant‐intensity bouts at a power output 10% above lactate threshold. Femoral nerve electrical stimulation was applied to elicit quadriceps twitch force both while pedaling (dynamic) and at rest (isometric). The test–retest reliability of the dynamic twitch forces and the agreement between the dynamic and isometric twitch forces were evaluated. Dynamic twitch force was found to have excellent reliability in an unfatigued state (intraclass correlation coefficient (ICC) = 0.920 and mean coefficient of variation (CV) = 7.5%), and maintained good reliability at task failure (ICC = 0.846 and mean CV = 11.5%). When comparing dynamic to isometric twitch forces across the task, there was a greater relative decline in the dynamic condition (P = 0.001). However, when data were normalized to the 5 min timepoint when potentiation between conditions was presumed to be more similar, this difference disappeared (P = 0.207). The reliability of this method was shown to be commensurate with the gold standard method utilizing seated isometric dynamometers and offers a new avenue to monitor the kinetics of muscle fatigue during cycling in real time. Highlights: The measurement of skeletal muscle fatigue during cycling exercise typically requires stopping the exercise task, potentially confounding the measurement, and limiting the frequency at which measurements can be madeWe have developed a novel method of assessing skeletal muscle fatigue which can be done while allowing cycling exercise to continue uninterruptedThe reliability of this method was shown to be commensurate with the gold standard method utilizing seated isometric dynamometers [ABSTRACT FROM AUTHOR]

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision‐making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi‐timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post‐labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi‐timepoint data can be acquired in the same scan time as single‐PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single‐PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi‐timepoint ASL and provides robust recommendations for acquiring high‐quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi‐timepoint ASL data. Furthermore, we review the potential clinical applications where multi‐timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article. [ABSTRACT FROM AUTHOR]

POLR3‐related hypomyelinating leukodystrophy (POLR3‐HLD) is a rare inherited neurological disorder caused by biallelic pathogenic variants in specific genes encoding subunits of RNA polymerase III (Pol III). Here, we report the third patient worldwide with pathogenic variants in POLR3K and clinical features consistent with POLR3‐HLD. The female patient presented with mild intellectual and behavioural disturbances in childhood, as well as growth delay, with brain MRI revealing diffuse hypomyelination and a pattern consistent with POLR3‐HLD. In adolescence, she manifested minor motor dysfunction. Next‐generation sequencing revealed a paternally inherited missense variant in POLR3K (c.322G>T; p.D108Y) and a maternally inherited large deletion, spanning approximately 17.8 kb from chr16:30,362‐48,162. The missense variant is located at the C‐terminus position of the protein and is predicted to impair residue interactions and cause steric interference in enzyme conformational changes. The large deletion encompasses the third and last exon of POLR3K, leading to a likely amorphic truncated protein product lacking the final 42 amino acids from the total 108 amino acid–length protein. Studies of RNA‐level expression showed a significant reduction in the levels of POLR3K RNA in the patient compared to the control. In considering whether the transcriptional function of Pol III was affected, the expression of several Pol III‐transcribed RNAs was measured, where the levels of several distinct tRNAs were significantly reduced in the patient while the expression of other RNA transcripts was not decreased, suggesting that Pol III retains partial function. This study provides further evidence for the association of pathogenic variants in POLR3K with POLR3‐HLD, expanding the spectrum of pathogenic variants in genes encoding for Pol III subunits associated with this disease. [ABSTRACT FROM AUTHOR]

There is a growing need to understand the potential ecological impacts of contaminants in offshore oil and gas infrastructure, especially if that infrastructure is to be left in situ as a decommissioning option. Naturally occurring radioactive material (NORM) is one type of contaminant found in solid deposits on internal surfaces of infrastructure that poses potential ecological harm if released into the marine environment. Microbes are important components of marine sediment ecosystems because they provide ecosystem services, yet the impacts of NORM contamination to these communities are not well understood. The present study aimed to investigate the response of benthic microbial communities to NORM‐contaminated scale, collected from an offshore oil and gas system, via controlled laboratory microcosm studies. Changes to microbial communities in natural sediment and sediments spiked with NORM at radium‐226 activity concentrations ranging from 9.5 to 59.8 Bq/kg (in partial equilibria with progeny) over 7 and 28 days were investigated using high‐throughput sequencing of environmental DNA extracted from experimental sediments. There were no significant differences in microbial community composition between control and scale‐spiked sediments over 7 and 28 days. However, we observed a greater presence of Firmicutes in the scale‐mixed treatment and Chloroflexi in the scale‐surface treatments after 28 days. This could suggest selection for species with contaminant tolerance or potential resilience to radiation and metal toxicity. Further research is needed to explore microbial tolerance mechanisms and their potential as indicators of effects of radionuclide‐contaminated sediments. The present study demonstrated that microcosm studies can provide valuable insights about the potential impacts of contamination from oil and gas infrastructure to sediment microbial communities. Environ Toxicol Chem 2024;43:1648–1661. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

This pilot study examined the process and outcome of Developmental Couple Therapy for Complex Trauma (DCTCT) with seven couples. DCTCT is a novel form of couple therapy designed to address complex posttraumatic stress disorder symptomatology and couple‐level distress in trauma survivors and their partners. These couples showed statistically significant improvements in overall trauma symptoms, emotion regulation capacities, and reductions in attachment‐related anxiety. These results suggest that DCTCT may be a promising approach to intervention. Future directions include the development of a sequential care model, because resource limitations may not allow for all couples to receive the full treatment model over 40 weeks; it will also be important to address measurement issues in relation to mentalizing, to allow for observational coding across the course of therapy. [ABSTRACT FROM AUTHOR]

The high prevalence of mental health problems and underutilization of mental health treatment are more severe among the Native Hawaiian and Other Pacific Islander (NHPI) populations and remain misunderstood and understudied. Examining mental health literacy (MHL) – the knowledge and beliefs about mental disorders – aids their recognition, management, or prevention – has been shown to identify barriers to seeking and receiving care. This study aimed to assess the level of MHL in NHPIs and identify associated demographic variables. Data for this cross‐sectional study were collected from 298 US NHPIs via an online questionnaire of the Mental Health Literacy Scale (MHLS). The overall mean MHLS score was 121 (SD = 17.3), with statistically significant higher scores in female participants, >31 years old, Tongan, more educated, and with higher income. This study demonstrated that overall MHL is comparable among NHPI compared to the current literature. However, NHPI men ≤30 years old and with lower income had lower MHL, which may be linked to the mental health disparities specific to this population. Current interventions should focus on increasing knowledge of risk factors, causes, self‐treatments, and available professional help regarding mental disorders. Efforts to improve the MHL of NHPI should target men ≤30 years with lower income (<$50 000). [ABSTRACT FROM AUTHOR]

INTRODUCTION: Hypertension and diabetes are common cardiovascular risk factors that increase Alzheimer's disease (AD) risk. However, it is unclear whether AD risk differs in hypertensive individuals with and without diabetes. METHODS: Cognitively normal individuals (N = 11,074) from the National Alzheimer's Coordinating Center (NACC) were categorized as having (1) hypertension with diabetes (HTN+/DM+), (2) hypertension without diabetes (HTN+/DM‐), or (3) neither (HTN‐/DM‐). AD risk in HTN+/DM+ and HTN+/DM‐ was compared to HTN‐/DM‐. This risk was then investigated in those with AD neuropathology (ADNP), cerebral amyloid angiopathy (CAA), cerebrovascular neuropathology (CVNP), arteriolosclerosis, and atherosclerosis. Finally, AD risk in HTN‐/DM+ was compared to HTN‐/DM‐. RESULTS: Seven percent (N = 830) of individuals developed AD. HTN+/DM+ (hazard ratio [HR] = 1.31 [1.19–1.44]) and HTN+/DM‐ (HR = 1.24 [1.17–1.32]) increased AD risk compared to HTN‐/DM‐. AD risk was greater in HTN+/DM+ with ADNP (HR = 2.10 [1.16–3.79]) and CAA (HR = 1.52 [1.09–2.12]), and in HTN+/DM‐ with CVNP (HR = 1.54 [1.17–2.03]). HTN‐/DM+ also increased AD risk (HR = 1.88 [1.30–2.72]) compared to HTN‐/DM‐. DISCUSSION: HTN+/DM+ and HTN+/DM‐ increased AD risk compared to HTN‐/DM‐, but pathological differences between groups suggest targeted therapies may be warranted based on cardiovascular risk profiles. Highlights: AD risk was studied in hypertensive (HTN+) individuals with/without diabetes (DM+/‐).HTN+/DM+ and HTN+/DM‐ both had an increased risk of AD compared to HTN‐/DM‐.Post mortem analysis identified neuropathological differences between HTN+/DM+ and HTN+/DM‐.In HTN+/DM+, AD risk was greater in those with AD neuropathology and CAA.In HTN+/DM‐, AD risk was greater in those with cerebrovascular neuropathology. [ABSTRACT FROM AUTHOR]

Aim: To explore the relationship between social care‐related quality of life (SCrQoL) for caregivers of a child with a developmental and epileptic encephalopathy (DEE; such as SCN2A and Dravet syndrome) and health literacy, illness perceptions, and caregiver activation. Method: As part of a larger pre‐post pilot study of an information linker service, caregivers completed a baseline questionnaire which included demographics and measures to assess SCrQoL, health literacy, illness perceptions, and caregiver activation. We used Spearman's Rho to determine relationships between variables. Results: Seventy‐two caregivers completed the questionnaire. Total SCrQoL varied widely, ranging from an 'ideal state' to 'high needs state'. Caregivers most frequently reported high needs regarding doing activities they enjoy and looking after themselves. Total SCrQoL was correlated with cognitive (r[70] = −0.414, p < 0.000) and emotional representations of illness (r[70] = −0.503, p < 0.000), but not coherence (r = −0.075, p = 0.529). Total SCrQoL was not correlated with health literacy (r[70] = 0.125, p = 0.295) or caregiver activation (r[70] = 0.181, p = 0.127). Interpretation: Future research should explore whether interventions that help caregivers cognitively reframe the negative experiences of having a child with a DEE, and support them to partake in activities they enjoy, boost their SCrQoL. What this paper adds: Caregiver social care‐related quality of life (SCrQoL) varied widely, from 'ideal state' to 'high needs state'.Most common high needs were doing enjoyable activities and self‐care.Caregivers with higher SCrQoL may perceive their child's illness as less threatening.SCrQoL does not appear to be related to caregiver activation in this sample. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. Objective: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). Methods: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13–20 years). Whole brain voxel‐wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex–diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). Results: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex‐by‐diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). Conclusion: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent‐onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted. [ABSTRACT FROM AUTHOR]

Background: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity. Objectives: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias. Methods: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population‐based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%–8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose‐lowering medications within 180 days." To address disease latency, 1‐year lag time was applied to the end of the 180‐day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity‐score weighted Cox proportional hazard models. Results: Over mean follow‐up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person‐years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96–1.15]), compared to delayed or no glucose‐lowering medication initiation (N = 22,369; 1768 events; 117,415 person‐years). Conclusion: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported. [ABSTRACT FROM AUTHOR]

Although knowledge of the functions of the gut microbiome has increased greatly over the past few decades, our understanding of the mechanisms governing its ecology and evolution remains obscure. While host genetic distance is a strong predictor of the gut microbiome in large‐scale studies and captive settings, its influence has not always been evident at finer taxonomic scales, especially when considering among the recently diverged animals in natural settings. Comparing the gut microbiome of 19 populations of Japanese macaques Macaca fuscata across the Japanese archipelago, we assessed the relative roles of host genetic distance, geographic distance and dietary factors in influencing the macaque gut microbiome. Our results suggested that the macaques may maintain a core gut microbiome, while each population may have acquired some microbes from its specific habitat/diet. Diet‐related factors such as season, forest, and reliance on anthropogenic foods played a stronger role in shaping the macaque gut microbiome. Among closely related mammalian hosts, host genetics may have limited effects on the gut microbiome since the hosts generally have smaller physiological differences. This study contributes to our understanding of the relative roles of host phylogeography and dietary factors in shaping the gut microbiome of closely related mammalian hosts. Research Highlights: Japanese macaques may maintain a core gut microbiome, while each population may have acquired some microbes from its specific habitat/diet.Among closely related mammalian hosts, host genetics may have limited effects on the gut microbiome since the hosts generally have smaller physiological differences.The effect of diet quality, which is influenced the forest type, season and reliance on anthropogenic foods, was more pronounced and may have affected the distribution of specific microbial taxa. [ABSTRACT FROM AUTHOR]

Background: Sulfonylureas are oral glucose‐lowering medications positioned as a second‐line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase‐4 (DPP4) inhibitor use. Methods: Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population‐based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity‐score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention‐to‐treat exposure definition. A separate propensity‐score weighted analysis was conducted to explore within‐class differences in dementia risk among sulfonylurea new users selected from the primary cohort. Results: Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person‐years; aHR [95% CI] = 1.09 [1.04–1.15]) over a mean follow‐up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03–1.32]). Conclusion: New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes. See related Editorial by Lee et al. in this issue. [ABSTRACT FROM AUTHOR]

Background: Neurological symptoms associated with coronavirus disease 2019 (COVID‐19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post‐COVID‐19 timeframe. Purpose: To determine whether adults who experienced flu‐like symptoms due to COVID‐19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu‐like symptoms but tested negative for COVID‐19. Study Type: Prospective observational. Population: A total of 39 adults who previously self‐isolated at home due to COVID‐19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu‐like symptoms but had a negative COVID‐19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). Field Strength and Sequences: A 3.0 T; T1‐weighted magnetization‐prepared rapid gradient and echo‐planar turbo gradient‐spin echo arterial spin labeling sequences. Assessment: Arterial spin labeling was used to estimate CBF. A self‐reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID‐19 and control groups and between those with (n = 11) and without self‐reported ongoing fatigue (n = 28) within the COVID‐19 group. Statistical Tests: Between‐group and within‐group comparisons of CBF were performed in a voxel‐wise manner, controlling for age and sex, at a family‐wise error rate of 0.05. Results: Relative to controls, the COVID‐19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t‐statistic = 5.21). Within the COVID‐19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self‐reported on‐going fatigue. Data Conclusion: These cross‐sectional data revealed regional CBF decreases in the COVID‐19 group, suggesting the relevance of brain physiology in the post‐COVID‐19 timeframe. This research may help elucidate the heterogeneous symptoms of the post‐COVID‐19 condition. Evidence Level: 2. Technical Efficacy: Stage 3. [ABSTRACT FROM AUTHOR]

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Background: Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known. Objective: We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD). Methods: Psoriasis patients (n = 37) with a history of moderate–severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis versus controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n = 76) versus without (n = 97) myocardial infarction (MI), and patients with peripheral artery disease (n = 106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed. Results: In psoriasis, median age was 44 (IQR; 34–51) years, 49% male and ACC/AHA ASCVD Risk Score of 1.0% (0.6–3.4) with no significant difference versus controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9–8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis versus controls (p < 0.05), and 1302 genes positively and 1244 genes negatively correlated with PASI (p < 0.05). Seventy‐three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL‐6, IL‐1β and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3 and STAT5A. Conclusions: A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation and CVD. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac‐related intracranial pulsatility may relate to cerebrovascular health, and this information is contained in BOLD MRI data. There is broad interest in methods to isolate BOLD pulsatility, and the current study examines a deep learning approach. Methods: Multi‐echo BOLD images, respiratory, and cardiac recordings were measured in 55 adults. Ground truth BOLD pulsatility maps were calculated with an established method. BOLD fast Fourier transform magnitude images were used as temporal‐frequency image inputs to a U‐Net deep learning model. Model performance was evaluated by mean squared error (MSE), mean absolute error (MAE), structural similarity index (SSIM), and mutual information (MI). Experiments evaluated the influence of input channel size, an age group effect during training, dependence on TE, performance without the U‐Net architecture, and importance of respiratory preprocessing. Results: The U‐Net model generated BOLD pulsatility maps with lower MSE as additional fast Fourier transform input images were used. There was no age group effect for MSE (P > 0.14). MAE and SSIM metrics did not vary across TE (P > 0.36), whereas MI showed a significant TE dependence (P < 0.05). The U‐Net versus no U‐Net comparison showed no significant difference for MAE (P = 0.059); however, SSIM and MI were significantly different between models (P < 0.001). Within the insula, the cross‐correlation values were high (r > 0.90) when comparing the U‐Net model trained with/without respiratory preprocessing. Conclusion: Multi‐echo BOLD pulsatility maps were synthesized from a U‐net model that was trained to use temporal‐frequency BOLD image inputs. This work adds to the deep learning methods that characterize BOLD physiological signals. [ABSTRACT FROM AUTHOR]

In this study, hyperpolarized 13C MRI (HP‐13C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13C‐pyruvate was administered to healthy aging individuals (N = 35, ages 21–77) and whole‐brain spatial distributions of 13C‐lactate and 13C‐bicarbonate production were measured. Linear mixed‐effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13C‐lactate and normalized 13C‐bicarbonate production with age: −7%±2% per decade for 13C‐lactate and −9%±4% per decade for 13C‐bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13C‐lactate versus age and a slightly increasing 13C‐bicarbonate versus age. The results show that both the production of lactate (visible as 13C‐lactate signal) as well as the consumption of monocarboxylates to make acetyl‐CoA (visible as 13C‐bicarbonate signal) decrease with age and that the rate of change varies by brain region. [ABSTRACT FROM AUTHOR]

There has been growing attention on the effect of COVID‐19 on white‐matter microstructure, especially among those that self‐isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single‐shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single‐shell‐compatible diffusion MRI modeling methods are compared for detecting the effect of COVID‐19, including diffusion‐tensor imaging, diffusion‐tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self‐isolated patients at the study initiation and 3‐month follow‐up, along with age‐ and sex‐matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single‐shell methods to demonstrate COVID‐19‐related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID‐19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID‐19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID‐19 related white‐matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b‐values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3‐month follow‐up, likely due to the limited size of the follow‐up cohort. To summarize, correlated diffusion imaging is shown to be a viable single‐shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID‐19 patients, suggesting the two regions react differently to viral infection. [ABSTRACT FROM AUTHOR]

Objective: Platelets are mediators of inflammation with immune effector cell properties and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet‐associated lectin, galactoside‐binding, soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE and as a potential biomarker associated with clinical phenotypes. Methods: We performed RNA sequencing on platelets from patients with SLE (n = 54) and on platelets from age‐, sex‐, and race/ethnicity‐matched healthy controls (n = 18) and measured LGALS3BP levels in platelet releasate and in circulating serum. We investigated the association between LGALS3BP levels and the prevalence, disease severity, and clinical phenotypes of SLE and studied platelet‐mediated effects on myeloid inflammation. Results: Platelets from patients with SLE exhibited increased expression of LGALS3BP (fold change 4.0, adjusted P = 6.02 × 10−11). Platelet‐released LGALS3BP levels were highly correlated with circulating LGALS3BP (R = 0.69, P < 0.0001), and circulating LGALS3BP levels were correlated with the severity of disease according to the SLE Disease Activity Index (r = 0.32, P = 0.0006). Specifically, circulating LGALS3BP levels were higher in SLE patients with lupus nephritis than in patients with inactive disease (4.0 μg/ml versus 2.3 μg/ml; P < 0.001). Interferon‐α induced LGALS3BP transcription and translation in a megakaryoblastic cell line (MEG‐01) in a dose‐dependent manner. Recombinant LGALS3BP and platelet releasates from SLE patients enhanced proinflammatory cytokine production by macrophages. Conclusions: Our results support that platelets act as potent effector cells that contribute to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity. [ABSTRACT FROM AUTHOR]

Background: There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in‐scanner single‐session nitrous oxide treatment of bipolar depression with repeated measures of CBF. Methods: In this double‐blind randomized controlled trial, 25 adults with BD I/II and current treatment‐refractory depression received either: (1) nitrous oxide (20 min at 25% concentration) plus intravenous saline (n = 12), or (2) medical air plus intravenous midazolam (2 mg total; n = 13). Study outcomes included changes in depression severity (Montgomery‐Asberg Depression Rating Scale scores, primary) and changes in CBF (via arterial spin labeling magnetic resonance imaging). Results: There were no significant between‐group differences in 24‐h post‐treatment MADRS change or treatment response. However, the nitrous oxide group had significantly greater same‐day reductions in depression severity. Lower baseline regional CBF predicted greater 24‐h post‐treatment MADRS reductions with nitrous oxide but not midazolam. In region‐of‐interest and voxel‐wise analyses, there was a pattern of regional CBF reductions following treatment with midazolam versus nitrous oxide. Conclusions: Present findings, while tentative and based on secondary endpoints, suggest differential associations of nitrous oxide versus midazolam with bipolar depression severity and cerebral hemodynamics. Larger studies integrating neuroimaging targets and repeated nitrous oxide treatment sessions are warranted. [ABSTRACT FROM AUTHOR]

Scotland, traditionally, has high levels of confidence in teachers. Fairness and justice are key concepts in policy and practice in Scottish education. For more than 100 years, the high‐stakes assessment system in Scotland, with the Scottish Higher qualification at its heart, has been crucial to that sense of opportunity and justice. However, in 2019–2020, public confidence in high‐stakes assessment in Scotland, as in other United Kingdom countries, was dented. In Scotland, the Covid‐19 pandemic meant that schools were closed, teachers provided online learning opportunities for pupils working at home and, for the first time in 130 years, it was not possible to run national examinations. To ensure that learners were not further disadvantaged, alternative approaches to gathering evidence for qualifications were instigated. However, these results were challenged as socially unjust and the results that had been nationally moderated were replaced by results based on locally moderated teachers' professional judgement. As Scotland looks to qualifications beyond Covid‐19, trust must be re‐built. This article reports on a participative research project that sought to understand public perceptions of standards and fairness across a range of key communities following this experience. Drawing on both qualitative and quantitative data, we analyse factors which affected trust in National Qualifications under the pandemic. The evidence suggests that when considering what matters for qualifications to be trusted, technocratic solutions are likely to be rejected by stakeholders. Understanding and responding to what led to the mistrust of qualifications in Scotland will be crucial to inform its future qualifications system. [ABSTRACT FROM AUTHOR]

Female primates represent the most important social partner for their developing offspring. However, mothers may strongly differ in the way they relate to their offspring (e.g., in terms of two different dimensions: protectiveness and rejection). In this study, we aimed to assess how dominance style predicts (i) changes in maternal behavior through offspring development, and (ii) the link between maternal behavior and offspring behavior. We conducted behavioral observations on 34 free‐ranging immatures of two species of macaques with different dominance styles: less tolerant Japanese macaques (JM; Macaca fuscata) and more tolerant moor macaques (MM; Macaca maura). Our results showed that maternal behavior differed between JM and MM: maternal proximity and grooming decreased through offspring development more quickly in MM than in JM, whereas maternal rejection and aggression, which were generally more frequent in JM, decreased with offspring age similarly in both species. In contrast, maternal restraint of offspring decreased similarly with offspring age in both species. Furthermore, dominance style was differentially associated with the link between maternal and offspring behavior: in MM only, maternal grooming predicted an increase of the probability that offspring interacted with partners other than their mothers and engaged in solitary play, whereas maternal rejection predicted a decrease in the occurrence of solitary play. Overall, these results suggest interspecific variation in maternal behavior during offspring's first years of life, and point to the possibility that these differences may have an important role in shaping their behavioral development. Highlights: Maternal protectiveness decreased with offspring age generally more quickly in moor macaques (MM) than in Japanese macaques (JM).Maternal rejection was more frequent in JM than in MM.In MM, higher maternal grooming and lower rejection were linked to more social and playful offspring.In JM, maternal grooming was linked to less social and playful offspring. [ABSTRACT FROM AUTHOR]

Background: The Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) is used to assess decline in memory, language, and praxis in Alzheimer's disease (AD). Methods: A latent state–trait model with autoregressive effects was used to determine how much of the ADAS‐Cog item measurement was reliable, and of that, how much of the information was occasion specific (state) versus consistent (trait or accumulated from one visit to the next). Results: Participants with mild AD (n = 341) were assessed four times over 24 months. Praxis items were generally unreliable as were some memory items. Language items were generally the most reliable, and this increased over time. Only two ADAS‐Cog items showed reliability >0.70 at all four assessments, word recall (memory) and naming (language). Of the reliable information, language items exhibited greater consistency (63.4% to 88.2%) than occasion specificity, and of the consistent information, language items tended to reflect effects of AD progression that accumulated from one visit to the next (35.5% to 45.3%). In contrast, reliable information from praxis items tended to come from trait information. The reliable information in the memory items reflected more consistent than occasion‐specific information, but they varied between items in the relative amounts of trait versus accumulated effects. Conclusions: Although the ADAS‐Cog was designed to track cognitive decline, most items were unreliable, and each item captured different amounts of information related to occasion‐specific, trait, and accumulated effects of AD over time. These latent properties complicate the interpretation of trends seen in ordinary statistical analyses of trials and other clinical studies with repeated ADAS‐Cog item measures. Highlights: Studies have described unfavorable psychometric properties of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog), bringing into question its ability to track changes in cognition uniformly over time. There remains a need to estimate how much of the ADAS‐Cog measurement is reliable, of that how much is occasion specific versus consistent, and of the consistent information, how much represents enduring traits versus autoregressive effects (i.e., effects of Alzheimer's disease [AD] progression carried over from one assessment to the next).A latent state–trait model with autoregressive effects in mild AD found most items to be unreliable, and each item to capture different amounts of occasion‐specific, trait, and autoregressive information. Language items, specifically, naming and the memory item word recall, were the most reliable.Psychometric idiosyncrasies of individual items complicate the interpretation of their summed score, biasing ordinary statistical analyses of repeated measures in mild AD. Future studies should consider item trajectories individually. [ABSTRACT FROM AUTHOR]

Gorilla tourism supports the protection of its ecosystem, benefiting humans and wildlife populations living therein. Assessing to what degree the presence and proximity of tourists affect wildlife aids long‐term benefits. Because wild animals might see human activities as stressors, we hypothesized that the increased presence and proximity of tourists leads to immediate changes in gorilla social cohesion. We constructed social networks from association rates before, during, and after tourist visits, and when tourists were very close (≤3 m) or close (>3 m) to them. Our analysis focused on this distance threshold (≤3 m and >3 m) because the 7 m rule, enforced by the national park, was violated 84% of the time. We showed that gorillas spent more time in closer association after tourists arrived and when tourists were <3 m away from gorillas. Immediate changes were detected in the number of individuals close to each other, the time they spent together and the distance of an individual to all others, indicating that gorillas might increase social cohesion because they perceive tourists as a risk. These results highlight the need to enforce the tourism guidelines (maximum of eight people per group, including park staff; minimum distance of 7 m) to ensure the sustainable success of gorilla tourism. [ABSTRACT FROM AUTHOR]

Background: Systemic vascular risk is a well‐established contributor to late‐life cognitive decline, yet the mechanism is not completely understood. We investigated whether neuroimaging‐based measures of vascular injury (white matter hyperintensity (WMH) volume, Peak width of Skeletonized Mean Diffusivity (PSMD), and relative cerebral blood flow (rCBF)) could explain the effect of systemic vascular risk on cognitive decline using longitudinal data from the Harvard Aging Brain Study. Method: We used the Framingham Heart Study cardiovascular disease risk score (FHS‐CVD) as an index of systemic vascular risk. We extracted WMH from structural MRI (https://hypermapp3r.readthedocs.io/) and PSMD from diffusion MRI (http://www.psmdmarker.com). We performed kinetic modeling on dynamically‐acquired PiB‐PET data to extract 1) amyloid burden as the distribution volume ratio (PiB‐DVR) and 2) relative tracer delivery (PiB‐R1 via MRTM reference‐tissue analysis as a proxy of rCBF). Global cognition was assessed using Preclinical Alzheimer Cognitive Composite (PACC). We considered two linear mixed effect models to examine whether cerebrovascular injury markers could explain the FHS‐CVD effect on PACC change over time: 1) FHS‐CVD on PACC change controlling for age, sex, years of education, and PiB‐DVR; 2) the previous model including WMH, PSMD, and PIB‐R1. Analyses were stratified by high (PiB+) and low (PiB‐) baseline amyloid burden. Result: Figure 1 illustrates the relationships between demographics and neuroimaging measures at baseline. Table 1 shows the demographics and study information. We observed a significant effect of FHS‐CVD on PACC change (PiB‐: t=‐3.9, p<0.001 (Table 2); PiB+: t=‐2.6, p=0.008). When the cerebrovascular injury markers were included in the model, the effect of FHS‐CVD was reduced in the PiB‐ group while PSMD and PiB‐R1 explained PACC change (Table 3; Figure 2). The second model fit was significantly better than the first model (L.ratio= 25.9, p<0.001). The effects remained significant after controlling for gray matter volume. In contrast, cerebrovascular injury measures did not explain the effect of FHS‐CVD on PACC change in the PIB+ group. Conclusion: These results demonstrate that cerebrovascular injury largely explains the effect of systemic vascular risk on cognitive decline in older adults with lower amyloid burden suggesting mechanisms by which a higher systemic vascular risk impacts brain function. [ABSTRACT FROM AUTHOR]

Rationale, Aims and Objectives: Clinical Practice Guidelines (CPGs) have been shown to improve healthcare services and clinical outcomes. However, they are useful resources only to the degree that they are developed according to the most rigorous standards. Multiple studies have demonstrated significant variability between CPGs with regard to specific indicators of quality. The Ordre des psychologues du Québec (OPQ), the College of psychologists of Quebec, has published several CPGs that are intended to provide empirically supported guidance for psychologists in the areas of assessment, diagnosis, general functioning, treatment and other decision‐making support. The aim of this study was to evaluate the quality of these CPGs. Methods: The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of the CPGs. Results: Our results show that although there have been some modest improvements in quality of the CPGs over time, there are important methodological inadequacies in all CPGs evaluated. Conclusions: The findings of this study demonstrate the need for more methodological rigour in CPGs development as such, recommendations to improve CPG quality are discussed. [ABSTRACT FROM AUTHOR]

Of note, the proband twin had 2 days of mild, subthreshold depressive symptoms in the week prior to MRI, whereas the co-twin and all healthy control participants were euthymic. The proband twin had lower CBF across all brain regions examined, including global CBF, compared to the co-twin and healthy controls. This article, augmented by the integration of neuroimaging, adds to the sparse number of case reports which focus on early-onset bipolar disorder and includes monozygotic twins. [Extracted from the article]

This is the second of a three-part series that explores different aspects of uncertainty, certainty and hope in the context of providing clinical care for children with rare and life-limiting neurological disorders. When caring for families impacted by an overwhelming complex disorder in a child, complicated by threatening uncertainties and potentially more threatening certainties, clinicians utilise skills drawn from differing fields to make the load of information, and the emotional impact more manageable. The first article in this series addressed how clinicians might manage the 'accumulation of uncertainties' and to provide compassionate care not only to their patients, and their families, but also to themselves. This second paper delves into the less helpful aspects of 'certainty', including the associated losses and griefs endured by parents responding to threatening fears associated with their child's condition. In the extreme, disconnection and psychological isolation borne by parents can lead to a sense of hopelessness and desperation. Facing unwelcome certainties - clinicians and parents together - forms the basis of future trust and hope. Clinicians who share the field of trust with families and show commitment to helping parents, even when cure remains elusive, build a sense of hope. This is the sort of hopefulness that clinicians need to have and to offer as they share the journey with families. In this series, we seek to harness a shared approach to face unwelcome certainties and to kindle a sense of hope that is both credible and meaningful to the parents, family and clinician. [ABSTRACT FROM AUTHOR]

This is the first of three articles exploring the aspects of clinical care for children with rare neurological disorders including uncertainties old and new. The disruptive technologies of genomic sequencing and advanced therapeutics such as gene-based therapies offer parents of children with severe but rare neurological conditions for the first-time unprecedented opportunities for 'precision medicine'. At the same time, the realities of limited genomic diagnostic yields and not infrequent detection of variants of uncertain significance, lack of natural history study data and management guidelines for individually rare neurogenetic conditions, means that high pre-genomic test expectations are all too often replaced by an accumulation of new uncertainties. This can add to the chronic traumatic stress experienced by many families but may also have under-recognised impacts for their clinicians, contributing to 'burn-out' and attendant negative psychosocial impacts. This first article aims to address how clinicians might manage the accumulation of uncertainties to be more helpful to patients and their families. Moreover, it seeks to address how clinicians can move forward providing compassionate care to their patients and a little more consideration for themselves. [ABSTRACT FROM AUTHOR]

Social structure can regulate information and pathogen transmission via social contact or proximity, which ultimately affects individual fitness. In theory, the social relationships that mediate information transmission also favor the spread of socially‐transmitted pathogens, creating a tradeoff between them. However, the mechanisms underlying the development and maintenance of individual relationships under such pressures remain underexplored. Here, we outline the evolutionary mechanisms of social transmission while presenting evidence that network plasticity results from individuals navigating between the costs and benefits of social relationships. We provide perspectives for the development of the field, considering this underexplored social tradeoff and the evolutionary processes underlying it. We believe that the study of the social transmission tradeoff has the potential to become a major new research direction in behavioural and evolutionary ecology. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet effects on the brain have not been well characterized at midlife. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. Two hundred and fifty‐four participants from the Coronary Artery Risk Development in Young Adults study were selected and stratified by WMH burden into Lo‐WMH (mean age = 50 ± 3.5 years) and Hi‐WMH (mean age = 51 ± 3.7 years) groups of equal size. We constructed group‐level covariance networks based on cerebral blood flow (CBF) and gray matter volume (GMV) maps across 74 gray matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo‐ and Hi‐WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no between‐group differences in either CBF or GMV covariance networks. In contrast, we found between‐group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence that WMH‐related network alterations are present at midlife. [ABSTRACT FROM AUTHOR]

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier‐free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well‐being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now. [ABSTRACT FROM AUTHOR]

Purpose: Develop and evaluate a deep learning approach to estimate cerebral blood flow (CBF) and arterial transit time (ATT) from multiple post‐labeling delay (PLD) ASL MRI. Methods: ASL MRI were acquired with 6 PLDs on a 1.5T or 3T GE system in adults with and without cognitive impairment (N = 99). Voxel‐level CBF and ATT maps were quantified by training models with distinct convolutional neural network architectures: (1) convolutional neural network (CNN) and (2) U‐Net. Models were trained and compared via 5‐fold cross validation. Performance was evaluated using mean absolute error (MAE). Model outputs were trained on and compared against a reference ASL model fitting after data cleaning. Minimally processed ASL data served as another benchmark. Model output uncertainty was estimated using Monte Carlo dropout. The better‐performing neural network was subsequently re‐trained on inputs with missing PLDs to investigate generalizability to different PLD schedules. Results: Relative to the CNN, the U‐Net yielded lower MAE on training data. On test data, the U‐Net MAE was 8.4 ± 1.4 mL/100 g/min for CBF and 0.22 ± 0.09 s for ATT. A significant association was observed between MAE and Monte Carlo dropout‐based uncertainty estimates. Neural network performance remained stable despite systematically reducing the number of input images (i.e., up to 3 missing PLD images). Mean processing time was 10.77 s for the U‐Net neural network compared to 10 min 41 s for the reference pipeline. Conclusion: It is feasible to generate CBF and ATT maps from 1.5T and 3T multi‐PLD ASL MRI with a fast deep learning image‐generation approach. [ABSTRACT FROM AUTHOR]

The energetics of cycling represents a well‐studied area of exercise science, yet there are still many questions that remain. Efficiency, broadly defined as the ratio of energy output to energy input, is one key metric that, despite its importance from both a scientific as well as performance perspective, is commonly misunderstood. There are many factors that may affect cycling efficiency, both intrinsic (e.g., muscle fiber type composition) and extrinsic (e.g., cycling cadence, prior exercise, and training), creating a complex interplay of many components. Due to its relative simplicity, the measurement of oxygen uptake continues to be the most common means of measuring the energy cost of exercise (and thus efficiency); however, it is limited to only a small proportion of the range of outputs humans are capable of, further limiting our understanding of the energetics of high‐intensity exercise and any mechanistic bases therein. This review presents evidence that delta efficiency does not represent muscular efficiency and challenges the notion that the slow component of oxygen uptake represents decreasing efficiency. It is noted that gross efficiency increases as intensity of exercise increases in spite of the fact that fast‐twitch fibers are recruited to achieve this high power output. Understanding the energetics of high‐intensity exercise will require critical evaluation of the available data. [ABSTRACT FROM AUTHOR]

4‐aminopyridine (4‐AP) is a potassium channel blocker that has been used to treat patients with multiple sclerosis and Lambert–Eaton disease. The concentration of this drug in the blood of patients was estimated to be in low or submicromolar range. Animal studies have shown that 4‐AP at such low concentration selectively blocks a subset of channels in Kv1 or Kv3 families. The crayfish opener neuromuscular junction and ventral superficial flexor (VSF) preparations were used to examine functions of K+ channels blocked by low concentrations of 4‐AP. At opener motor axons, intracellular recordings show that 4‐AP could increase action potential (AP) amplitude, duration, and after‐depolarization (ADP) at 10 μM. As 4‐AP concentration was increased, in twofold steps, AP amplitude did not increase further up to 5 mM. AP duration and ADP increased significantly mainly in two concentration ranges, 10–50 μM and 1–5 mM. The effects of 50 μM 4‐AP on the VSF were less consistent than that observed at the opener motor axons. 4‐AP did not change AP amplitude of motor axons recorded with an extracellular electrode and change in AP repolarizing potential was observed in ∼25% of the axons. EPSP recorded simultaneously with AP showed an increase in amplitude with 4‐AP treatment only in 30% of the axon‐EPSP pairs. 4‐AP also increased firing frequencies of ∼50% of axons. In four animals, 4‐AP "awakened" the firing of APs from an axon that was silent before the drug. The mixture of positive and negative 4‐AP effects summarized above was observed in the same VSF preparations in all cases (n = 8). We propose that there is a significant diversity in the density 4‐AP‐sensitive potassium channels among motor axons of the VSF. Functional significance in the differences of 4‐AP sensitivity of the two motor systems is discussed. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate a plyometric conditioning activity (3 sets of 5 countermovement jumps, [CA]) for twitch properties and voluntary knee extension. Methods: After a familiarization session, fourteen highly trained sprint athletes, 12 men (23.25 ± 7.17 years) and 2 women (23.0 ± 2.8 years) performed 2 experiments, each in a randomized order (crossover design). In one experiment, the time-course of twitch contractile properties was evaluated with and without the previous CA at 2, min intervals to 10 min of recovery. In the second session, maximal voluntary knee extension was evaluated at the same recovery intervals, for control and experimental condition in random order. Results: Mixed-model ANOVA with Bonferroni post-hoc revealed significant differences between pre-test and 2 min (p < 0.01, ES = 0.42) and 4 min (p < 0.01, ES = 0.20) for peak twitch torque of quadriceps femoris muscles confirming postactivation potentiation [PAP] at these times. Twitch rate of torque development (RTD) was significantly greater than pre-test value only at 2 min (p < 0.01, ES = 0.58) after the CA. Twitch contraction time and ½ relaxation time were not significantly difference from pre-test values after the CA (p > 0.05). No significant difference was observed for voluntary RTD following CA. Conclusion: The plyometric CA increased twitch peak torque and RTD consistent with PAP; however, there was no effect of CA on voluntary RTD of knee extension at any time after the plyometric CA. Even with PAP confirmed, we observed that the CA fails to improve isometric RTD of quadriceps femoris muscles. A plyometric CA significantly increased twitch peak torque (at 2 and 4 min) and twitch rate of torque development (at 2 min) of quadriceps femoris muscles, indicating postactivation potentiation (PAP). No effect was observed for twitch contraction time and ½ relaxation time after the CA. No improvement was observed on voluntary rate of torque development evaluated at the same time intervals. [ABSTRACT FROM AUTHOR]

Objectives: Atypical tooth wear, including macroscopically visible striations on anterior teeth and within root grooves on posterior teeth, are often regarded as evidence of non‐masticatory, tool use behavior in fossil hominins. Both these types of dental tissue loss are often considered unique to the genus Homo and suggested to be the earliest evidence of human cultural habits. The aim of this study was to describe similar tooth wear found in a wild primate population and to conduct a differential diagnosis of this atypical tissue loss. Materials and Methods: The focus of this study was a sample of wild Japanese macaques from Koshima Island, Japan. Individuals were provisioned regularly on the beach as part of one of the longest running primate field sites. Tooth wear and fractures in this group were compared to two other non‐provisioned populations. Information on diet and behavior were obtained from extensive literature and on‐going field observations. Results: All Koshima Island individuals analyzed showed atypical tooth wear. Large macroscopic striations were visible on many teeth, with sub‐vertical striations prominent on the labial surfaces of incisors. Root grooves on posterior teeth were observed in half of the individuals, some showing clear directional striations similar to those reported in "toothpick" grooves in fossil hominins. Tool use and the habitual insertion of non‐masticatory items in the mouth has not been observed in this population. Discussion: Accidental ingestion of sand and oral processing of marine mollusks likely creates these atypical wear patterns. Implications for similar wear that has been associated with tool‐use in fossil hominin samples were discussed. [ABSTRACT FROM AUTHOR]

Background: Youth with bipolar disorder (BD) are at greatly elevated risk for suicide. Self‐harm, encompassing all self‐injurious behaviors regardless of suicidal intent, is among one of the greatest risk factors for death by suicide. This study aims to extend the sparse literature regarding the neurostructural correlates of self‐harm in youth with BD. Methods: Participants included 156 youth (17.14 ± 1.61 years): 38 BD with lifetime history of self‐harm (BDSH+), 43 BD without history of self‐harm (BDSH−), and 75 healthy controls (HC). Measures of cortical thickness, surface area (SA), and volume were obtained using 3 T magnetic resonance imaging. Orbitofrontal and ventrolateral prefrontal cortices were examined in region‐of‐interest (ROI) analyses, complemented by exploratory vertex‐wise analyses using a general linear model controlling for age, sex, and intracranial volume. Results: In ROI analyses, there were no between‐group differences after correction for multiple comparisons. Vertex‐wise analysis revealed three significant clusters in precentral gyrus SA, inferior temporal gyrus SA, and caudal middle frontal gyrus volume. Post‐hoc vertex‐wise analyses showed BDSH+ had lower cortical SA and volume compared with both BDSH− and HC for all clusters. Conclusions: Significant vertex‐wise findings were observed in frontotemporal regions relevant to BD and self‐harm, with smaller neurostructural measures among BDSH+ compared with both BDSH− and HC. Future studies are needed to evaluate the temporal nature of the relationship of these neurostructural differences (i.e., potential risk indicators) to self‐harm and to identify mechanisms underlying these findings. [ABSTRACT FROM AUTHOR]