ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Curious Choices: Infants’ moment-to-moment information sampling is driven by their exploration history

Infants explore the world around them based on their intrinsically motivated curiosity. However, the cognitive mechanisms underlying such curiosity-driven exploratory behaviour remain largely unknown. Here, infants could freely explore two novel categories, triggering a new exemplar from a category by fixating on either of the two associated areas on a computer screen. This gaze-contingent design enabled us to distinguish between exploration – switching from one category to the other – and exploitation – consecutively triggering exemplars from the same category. Data from 10-12-month-old infants (N=68) indicated that moment-to-moment sampling choices were non-random but guided by the infants’ exploration history. Self-generated sequences grouped into three clusters of more explorative, exploitative, and balanced sampling patterns. Bayesian hierarchical binomial regression models indicated that across sequence patterns, infants’ longer trigger time, shorter looking time, and more gaze-shifting were associated with trial-by-trial decisions to disengage from exploiting one category and making an exploratory switch, especially after consecutively viewed stimuli of high similarity. These findings offer novel insights into infants’ curiosity-driven exploration and pave the way for future investigations, also regarding individual differences

The Infant and Toddler Curiosity Questionnaire: A validated caregiver-report measure of curiosity in children from 5 to 24 months

Humans are curious. Especially children are known for their drive to explore and learn, which is crucial for developing in and navigating through our complex world. Naturally, some children may be more curious than others, leading to differences in how they structure their own learning experiences, subsequently impacting their developmental trajectories. However, there is a gap in the research field for a reliable measure of such differences early in development. Across three studies, we present the development and assessment of the Infant and Toddler Curiosity Questionnaire (ITCQ), the first caregiver report measure to fill this gap. Items cover observable exploration behaviours in 5- to 24-month-olds to capture general tendencies of their desire to actively explore their immediate surroundings and are evaluated on a 7-point Likert-scale. Exploratory factor analyses and structural equation modelling on a sample of N = 370 UK caregivers led to the final selection of 23 items and provided evidence that the scale is unidimensional enough to allow for an overall curiosity score, whereas three emergent sub-factors of exploration types (sensory, investigative, and social exploration) showed acceptable internal consistency explaining additional variance in the data. Furthermore, the scale had good test-retest reliability after 7 to 14 days (N = 67) and related to the child’s temperament (N = 75; positively with surgency and effortful control, negatively with negative affect) offering evidence of its validity as a trait measure. Together, these results strongly support the scale’s reliability and validity, showcasing the ITCQ as a powerful tool for developmental research

Highly Sensitive Detection of Inorganic Contamination

As the detection of inorganic contaminants is of steadily increasing importance for the improvement of yields in microelectronic applications, the aim of one of the joint research activity within the European Integrated Activity of Excellence and Networking for Nano- and Micro-Electronics Analysis (ANNA, site: www.ANNA-i3.org) is the development and assessment of new methodologies and metrologies for the detection of low concentration inorganic contaminants in silicon and in novel materials. A main objective consist in the benchmarking of various analytical techniques available in the laboratories of the participating ANNA partners, including the improvement of the respective detection limits as well as the quantitation reliablity of selected analytical techniques such as total-reflection x-ray fluorescence (TXRF) analysi