SARS-CoV-2 is associated with changes in brain structure in UK Biobank.

There is strong evidence of brain-related abnormalities in COVID-191-13. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51-81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans-with 141 days on average separating their diagnosis and the second scan-as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.

Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non-AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three-dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non-AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. KEY POINTS: The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.

Innovating a Community-driven Enumeration and Needs Assessment of People Experiencing Homelessness: A Network Sampling Approach for the HUD-Mandated Point-in-Time Count.

To enumerate people experiencing homelessness in the U.S., the federal Department of Housing and Urban Development (HUD) mandates its designated local jurisdictions regularly conduct a crude census of this population. This Point-in-Time (PIT) body count, typically conducted on a January night by volunteers with flashlights and clipboards, is often followed by interviews with a separate convenience sample. Here, we propose employing a network-based (peer-referral) respondent-driven sampling (RDS) method to generate a representative sample of unsheltered people, accompanied by a novel method to generate a statistical estimate of the number of unsheltered people in the jurisdiction. First, we develop a power analysis for the sample size of our RDS survey to count unsheltered people experiencing homelessness. Then, we conducted three large-scale population-representative samples in King County, WA (Seattle metro) in 2022, 2023, and 2024. We describe the data collection and the application of our new method, comparing the 2020 PIT count (the last visual PIT count performed in King County) to the new method 2022 and 2024 PIT counts. We conclude with a discussion and future directions.

CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Ceramic-metal composites for heat exchangers in concentrated solar power plants.

The efficiency of generating electricity from heat using concentrated solar power plants (which use mirrors or lenses to concentrate sunlight in order to drive heat engines, usually involving turbines) may be appreciably increased by operating with higher turbine inlet temperatures, but this would require improved heat exchanger materials. By operating turbines with inlet temperatures above 1,023 kelvin using closed-cycle high-pressure supercritical carbon dioxide (sCO2) recompression cycles, instead of using conventional (such as subcritical steam Rankine) cycles with inlet temperatures below 823 kelvin1-3, the relative heat-to-electricity conversion efficiency may be increased by more than 20 per cent. The resulting reduction in the cost of dispatchable electricity from concentrated solar power plants (coupled with thermal energy storage4-6) would be an important step towards direct competition with fossil-fuel-based plants and a large reduction in greenhouse gas emissions7. However, the inlet temperatures of closed-cycle high-pressure sCO2 turbine systems are limited8 by the thermomechanical performance of the compact, metal-alloy-based, printed-circuit-type heat exchangers used to transfer heat to sCO2. Here we present a robust composite of ceramic (zirconium carbide, ZrC) and the refractory metal tungsten (W) for use in printed-circuit-type heat exchangers at temperatures above 1,023 kelvin9. This composite has attractive high-temperature thermal, mechanical and chemical properties and can be processed in a cost-effective manner. We fabricated ZrC/W-based heat exchanger plates with tunable channel patterns by the shape-and-size-preserving chemical conversion of porous tungsten carbide plates. The dense ZrC/W-based composites exhibited failure strengths of over 350 megapascals at 1,073 kelvin, and thermal conductivity values two to three times greater than those of iron- or nickel-based alloys at this temperature. Corrosion resistance to sCO2 at 1,023 kelvin and 20 megapascals was achieved10 by bonding a copper layer to the composite surface and adding 50 parts per million carbon monoxide to sCO2. Techno-economic analyses indicate that ZrC/W-based heat exchangers can strongly outperform nickel-superalloy-based printed-circuit heat exchangers at lower cost.

Early Candida colonisation impact on patients and healthcare professionals in an intensive care unit.

OBJECTIVES: Candida spp. is an opportunistic pathogen that causes superficial and invasive infections with nosocomial outbreaks without strict hygiene protocols. Herein, we assessed oral colonisation by Candida spp. in 209 Intensive Care Unit (ICU) patients between July 2021 and April 2022, conducting clinical, epidemiological, and microbiological characterisation of those developing oral or invasive candidiasis. METHODS: Initial oral swabs were collected within 24 h of admission in the ICU, followed by collections on Days 2, 4, 6 and 8. Swabs from denture-wearing patients, abiotic surfaces, healthcare professionals' hands, and retroauricular regions were also obtained. Recovered yeasts and filamentous fungi were identified using MALDI-TOF MS and morphological characteristics, respectively. Genetic similarity of Candida spp. isolates was evaluated using Amplified fragment length polymorphism (AFLP), and the antifungal susceptibility profile was determined by broth microdilution. RESULTS: In the study, 64.11% of patients were orally colonised by Candida spp. Of these, 80.59% were colonised within the first 24 h. Oral colonisation also occurred on subsequent days: 50%/Day 2, 26.92%/Day 4, and 11.53%/Days 6 and 8. Of the patients, 8.61% had oral candidiasis, mainly pseudomembranous. Among orally colonised patients, 2.23% developed invasive candidiasis. Besides, 89.47% of healthcare professionals evaluated were colonised. MALDI-TOF MS identified different yeast species, and C. albicans (45.34%), C. tropicalis (15.7%), and C. parapsilosis sensu stricto (9.88%) were the most prevalent. AFLP analysis indicated a high genetic correlation (≥97%) between C. parapsilosis sensu stricto isolates from patients and professionals. Three resistant C. albicans isolates were also found. CONCLUSION: This study reported a diversity of yeast and filamentous fungi species in ICU patients and highlighted early Candida spp. colonisation risks for invasive candidiasis, as well as the potential horizontal transmission in the nosocomial setting, emphasising the need for effective infection control measures.

Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Distributional justice and climate risk assessment: An analysis of disparities within direct and indirect risk.

Climate change and natural hazard risk assessments often overlook indirect impacts, leading to a limited understanding of the full extent of risk and the disparities in its distribution across populations. This study investigates distributional justice in natural hazard impacts, exploring its critical implications for environmental justice, equity, and resilience in adaptation planning. We employ high-resolution spatial risk assessment and origin-destination routing to analyze coastal flooding and sea-level rise scenarios in Aotearoa New Zealand. This approach allows the assessment of both direct impacts (property exposure) and indirect impacts (physical isolation from key amenities) on residents. Indirect impacts, such as isolation and reduced access to resources, have significant adverse effects on well-being, social cohesion, and community resilience. Including indirect impacts in risk assessments dramatically increases the overall population burden, while revealing complex effects on existing inequalities. Our analysis reveals that including indirect impacts increases the overall population burden, but the effect on inequalities varies. These inequalities can be exacerbated or attenuated depending on scale and location, underscoring the need for decision-makers to identify these nuanced distributions and apply context-specific frameworks when determining equitable outcomes. Our findings uncover a substantial number of previously invisible at-risk residents-from 61,000 to 217,000 nationally in a present-day event-and expose a shift in impact distribution toward underserved communities. As indirect risks exacerbate disparities and impede climate adaptation efforts, adopting an inclusive approach that accounts for both direct and indirect risks and their [un]equal distribution is imperative for effective and equitable decision-making.

Effects of the replacement corn meal by whole mango meal on tambaqui (Colossoma macropomum) diet: Digestibility, growth performance, biochemical, and hematological responses.

This study evaluated the digestibility of whole mango (Mangifera indica) meal (WMM) and determined the growth performance, intestinal enzyme activity, and metabolic and hematologic responses of tambaqui (Colossoma macropomum) juveniles fed diets containing different proportions of corn meal (CM) substitution by WMM. Fish fed with graded levels of WMM (0 (control), 80, 160, 240, and 320 g kg diet-1), replacing part of the dietary CM. The apparent digestibility coefficients of WMM were above 96%. Diets with WMM did not affect growth performance or intestinal enzyme activity. However, they showed a positive linear effect on plasma glucose, amino acids, and albumin levels and a negative linear effect on hepatic aspartate aminotransferase activity and hepatic glycogen, plasma cholesterol, and hemoglobin levels. Increased erythrocyte values and decreased plasma triglyceride levels were verified in fish fed 80 and 160 g WMM kg diet-1. In conclusion, the WMM may be a viable alternative to the tambaqui juveniles' diet, and WMM could replace up to 16% of CM without harming the growth and health of tambaqui juveniles.

Managing assessment during curriculum change: Ottawa Consensus Statement.

Curriculum change is relatively frequent in health professional education. Formal, planned curriculum review must be conducted periodically to incorporate new knowledge and skills, changing teaching and learning methods or changing roles and expectations of graduates. Unplanned curriculum evolution arguably happens continually, usually taking the form of "minor" changes that in combination over time may produce a substantially different programme. However, reviewing assessment practices is less likely to be a major consideration during curriculum change, overlooking the potential for unintended consequences for learning. This includes potentially undermining or negating the impact of even well-designed and important curriculum changes. Changes to any component of the curriculum "ecosystem "- graduate outcomes, content, delivery or assessment of learning - should trigger an automatic review of the whole ecosystem to maintain constructive alignment. Consideration of potential impact on assessment is essential to support curriculum change. Powerful contextual drivers of a curriculum include national examinations and programme accreditation, so each assessment programme sits within its own external context. Internal drivers are also important, such as adoption of new learning technologies and learning preferences of students and faculty. Achieving optimal and sustainable outcomes from a curriculum review requires strong governance and support, stakeholder engagement, curriculum and assessment expertise and internal quality assurance processes. This consensus paper provides guidance on managing assessment during curriculum change, building on evidence and the contributions of previous consensus papers.

Classical guitar intonation and compensation: The well-tempered guitar.

An intuitive model of classical guitar intonation is presented that includes the effects of the resonant length of the fretted string, linear mass density, tension, and bending stiffness. An expression is derived for the vibration frequencies of a stiff string using asymmetric boundary conditions at the saddle and the fret. Based on logarithmic frequency differences ("cents") that decouple these physical effects, Taylor series expansions are introduced that exhibit clearly the origins of frequency deviations of fretted notes from the corresponding 12-tone equal temperament (12-TET) values. A simple in situ technique is demonstrated for measurement of the changes in frequency of open strings arising from small adjustments in length, and a simple procedure is proposed that any interested guitarist can use to estimate the corresponding frequency shifts due to tension and bending stiffness for their own guitars and string sets. Based on these results, a least-squares fit method is employed to select values of saddle and nut setbacks that map fretted frequencies-for a particular string set and guitar-almost perfectly onto their 12-TET targets. A general approach to tempering an "off-the-shelf" guitar is shown to further reduce the tonal errors inherent in any fretted musical instrument.

Assessing the reach and engagement with the 'How To Save A Life' mass media campaign on drug-related death prevention in Scotland.

'How To Save A Life' (HTSAL) was a mass media campaign on drug-related death prevention which ran in Scotland from August 2021 to January 2022. It aimed to increase awareness of how to respond to an opioid overdose, and the uptake of take-home naloxone (THN). The objective of this study was to determine the reach and engagement with the campaign. Methods included a descriptive analysis of data from media sources, the campaign website, and an online naloxone training course. A quantitative content analysis was conducted on media articles. The campaign generated 57,402,850 non-unique impressions (the total number of times the campaign was seen or heard), and unique reach (the number of people who were exposed to the campaign) figures of 2,621,450. Engagement with the campaign was positive, and 96% of print/digital media articles had a positive view of the campaign. There were 40,714 visits to the campaign website, leading to 8,107 clicks to the free naloxone training course, and 3,141 clicks to order a free naloxone kit. This study showed that mass media campaigns on drug policy topics can achieve high levels of reach and engagement. There was a clear progression from viewing campaign materials, to visiting the campaign website, to completing naloxone training. Our research suggests that mass media campaigns can be used to disseminate harm reduction messages to the general public.

Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Multimodal study of the neural sources of error monitoring in adolescents and adults.

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-related potentials (ERPs) in 12-year-old, 15-year-old, and adult participants. Neural generators of two components related to performance and error monitoring, the N2 and ERN, lay within specific areas of fMRI clusters. Whereas correlates of the N2 component appeared similar across age groups, age-related differences manifested in the location of the generators of the ERN component. The dorsal anterior cingulate cortex (dACC) was the predominant source location for the 12-year-old group; this area manifested posteriorly for the 15-year-old and adult groups. A fMRI-based ROI analysis confirmed this pattern of activity. These results suggest that changes in the underlying neural mechanisms are related to developmental changes in performance monitoring.

Adverse childhood experiences and clustering of high-risk behaviors among high school students: a cross-sectional study.

OBJECTIVES: This study assessed the association between adverse childhood experiences (ACEs) and clustering of high-risk behaviors in a sample of high school students. STUDY DESIGN: This was a cross-sectional study. METHODS: A sample of students who attended randomly selected classes in 99 high schools completed the 2019 Nevada Youth Risk Behavior Survey (N = 4959). The survey included six ACE measures: (1) physical abuse, (2) sexual abuse, (3) verbal abuse, (4) household physical abuse, (5) household mental illness, and (6) household substance abuse. Students were assigned a cumulative ACE score (range = 0-6). A count of high-risk behavior domains was created using multiple questions across the following domains: (1) violence behaviors, (2) suicidal indicators, (3) non-suicidal self-injury, (4) substance use, (5) high-risk sexual behaviors, (6) poor diet, (7) physical inactivity, and (8) high screen time (range = 0-8). The relationship between ACEs and the count of high-risk behavior domains was assessed using weighted negative binomial regression; incidence rate ratios (IRRs) were calculated adjusting for sociodemographic characteristics. RESULTS: More than 40% of the sampled students reported high-risk behaviors across two or more domains. There was a strong, graded relationship between cumulative ACE score and the count of high-risk behavior domains. Compared with students who experienced zero ACEs, there was an increase in the count of high-risk behavior domains among students who experienced one ACE (adjusted IRR [aIRR] = 1.22, 95% confidence interval [CI] = 1.12-1.33), two ACEs (aIRR = 1.57, 95% CI = 1.42-1.73), three ACEs (aIRR = 1.73, 95% CI = 1.54-1.94), four ACEs (aIRR = 2.07, 95% CI = 1.84-2.33), five ACEs (aIRR = 2.69, 95% CI = 2.34-3.10), and six ACEs (aIRR = 2.91, 95% CI = 2.34-3.62). CONCLUSION: Trauma-informed prevention efforts may be an efficient way to address multiple adolescent risk behaviors that cluster.

Characterization of a new anellovirus species infecting an ocelot (Leopardus pardalis) in Brazil.

A complete genome of the first anellovirus infecting the wild felid Leopardus pardalis (ocelot) and a partial genome were assembled and annotated through high-throughput sequencing protocols followed by Sanger sequencing validation. The full-length virus obtained comprises 2,003 bp, while the partial genome comprises 1,224 bp. Phylogenetic analysis grouped these two sequences in two distinct clusters related to previously described Felidae anelloviruses. The ORF1 of the partial genome was identified as a new species provisionally called Torque teno ocelot virus, with 53.6% identity with its sister lineage. The complete genome was inferred as a new representative of the Torque teno felid virus 3 species, with 73.28% identity to the closest reference. This study expands known virus diversity and the host span of anelloviruses.

Multimodal Imaging Brain Markers in Early Adolescence Are Linked with a Physically Active Lifestyle.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence.SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development.

The Enhancing NeuroImaging Genetics through Meta-Analysis Consortium: 10 Years of Global Collaborations in Human Brain Mapping.

This Special Issue of Human Brain Mapping is dedicated to a 10-year anniversary of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. It reports updates from a broad range of international neuroimaging projects that pool data from around the world to answer fundamental questions in neuroscience. Since ENIGMA was formed in December 2009, the initiative grew into a worldwide effort with over 2,000 participating scientists from 45 countries, and over 50 working groups leading large-scale studies of human brain disorders. Over the last decade, many lessons were learned on how best to pool brain data from diverse sources. Working groups were created to develop methods to analyze worldwide data from anatomical and diffusion magnetic resonance imaging (MRI), resting state and task-based functional MRI, electroencephalography (EEG), magnetoencephalography (MEG), and magnetic resonance spectroscopy (MRS). The quest to understand genetic effects on human brain development and disease also led to analyses of brain scans on an unprecedented scale. Genetic roadmaps of the human cortex were created by researchers worldwide who collaborated to perform statistically well-powered analyses of common and rare genetic variants on brain measures and rates of brain development and aging. Here, we summarize the 31 papers in this Special Issue, covering: (a) technical approaches to harmonize analysis of different types of brain imaging data, (b) reviews of the last decade of work by several of ENIGMA's clinical and technical working groups, and (c) new empirical papers reporting large-scale international brain mapping analyses in patients with substance use disorders, schizophrenia, bipolar disorders, major depression, posttraumatic stress disorder, obsessive compulsive disorder, epilepsy, and stroke.

ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.