Orbitofrontal cortex hypergyrification in hallucinating schizophrenia patients: Surface ratio as a promising brain biomarker.

The study of brain gyrification may provide useful information on the cytoarchitecture and connectivity of the brain. One of the methods that have been developed to estimate brain gyrification, known as surface ratio (SR), has not yet been studied in schizophrenia. Here we aimed to assess whether SR could provide new insights on the brain structure of schizophrenia patients and the severity of symptoms. We also computed a more established brain gyrification measure, namely absolute mean curvature (AMC). We analyzed 63 magnetic resonance images, 25 from schizophrenia patients with treatment-resistant auditory verbal hallucinations (SCH-H), 18 from schizophrenia patients without hallucinations (SCH-NH), and 20 from healthy controls (HC). The SR measure revealed that SCH-H patients had a more folded orbitofrontal cortex than SCH-NH patients and HC. Gyrification in this region was also negatively associated with positive symptoms, specifically with the delusions and conceptual disorganization items, only in the SCH-H group. Regarding the AMC measure, we identified two areas where HC showed more gyrification than SCH-H patients, but no relationships arose with symptoms. The hypergyrification of the orbitofrontal cortex displayed by SCH-H patients, as captured by the SR measure, suggests aberrant and/or excessive wiring in these patients, which in turn could give rise to auditory verbal hallucinations. Alternatively, we comment on potential compensatory mechanisms that may better explain the negative association between orbitofrontal gyrification and positive symptomatology. The SR measure captured the most relevant differences and associations, making it a promising biomarker in schizophrenia.

Risks of infectious disease hospitalisations in the aftermath of tropical cyclones: a multi-country time-series study.

BACKGROUND: The proportion of intense tropical cyclones is expected to increase in a changing climate. However, there is currently no consistent and comprehensive assessment of infectious disease risk following tropical cyclone exposure across countries and over decades. We aimed to explore the tropical cyclone-associated hospitalisation risks and burden for cause-specific infectious diseases on a multi-country scale. METHODS: Hospitalisation records for infectious diseases were collected from six countries and territories (Canada, South Korea, New Zealand, Taiwan, Thailand, and Viet Nam) during various periods between 2000 and 2019. The days with tropical cyclone-associated maximum sustained windspeeds of 34 knots or higher derived from a parametric wind field model were considered as tropical cyclone exposure days. The association of monthly infectious diseases hospitalisations and tropical cyclone exposure days was first examined at location level using a distributed lag non-linear quasi-Poisson regression model, and then pooled using a random-effects meta-analysis. The tropical cyclone-attributable number and fraction of infectious disease hospitalisations were also calculated. FINDINGS: Overall, 2·2 million people who were hospitalised for infectious diseases in 179 locations that had at least one tropical cyclone exposure day in the six countries and territories were included in the analysis. The elevated hospitalisation risks for infectious diseases associated with tropical cyclones tended to dissipate 2 months after the tropical cyclone exposure. Overall, each additional tropical cyclone day was associated with a 9% (cumulative relative risk 1·09 [95% CI 1·05-1·14]) increase in hospitalisations for all-cause infectious diseases, 13% (1·13 [1·05-1·21]) for intestinal infectious diseases, 14% (1·14 [1·05-1·23]) for sepsis, and 22% (1·22 [1·03-1·46]) for dengue during the 2 months after a tropical cyclone. Associations of tropical cyclones with hospitalisations for tuberculosis and malaria were not significant. In total, 0·72% (95% CI 0·40-1·01) of the hospitalisations for all-cause infectious diseases, 0·33% (0·15-0·49) for intestinal infectious diseases, 1·31% (0·57-1·95) for sepsis, and 0·63% (0·10-1·04) for dengue were attributable to tropical cyclone exposures. The attributable burdens were higher among young populations (aged ≤19 years) and male individuals compared with their counterparts, especially for intestinal infectious diseases. The heterogeneous spatiotemporal pattern was further revealed at the country and territory level-tropical cyclone-attributable fractions showed a decreasing trend in South Korea during the study period but an increasing trend in Viet Nam, Taiwan, and New Zealand. INTERPRETATION: Tropical cyclones were associated with persistent elevated hospitalisation risks of infectious diseases (particularly sepsis and intestinal infectious diseases). Targeted interventions should be formulated for different populations, regions, and causes of infectious diseases based on evidence on tropical cyclone epidemiology to respond to the increasing risk and burden. FUNDING: Australian Research Council, Australian National Health, and Medical Research Council.

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

BACKGROUND: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. METHODS AND FINDINGS: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.

The social costs of tropical cyclones.

Tropical cyclones (TCs) can adversely affect economic development for more than a decade. Yet, these long-term effects are not accounted for in current estimates of the social cost of carbon (SCC), a key metric informing climate policy on the societal costs of greenhouse gas emissions. We here derive temperature-dependent damage functions for 41 TC-affected countries to quantify the country-level SCC induced by the persistent growth effects of damaging TCs. We find that accounting for TC impacts substantially increases the global SCC by more than 20%; median global SCC increases from US$ 173 to US$ 212 per tonne of CO2 under a middle-of-the-road future emission and socioeconomic development scenario. This increase is mainly driven by the strongly TC-affected major greenhouse gas emitting countries India, USA, China, Taiwan, and Japan. This suggests that the benefits of climate policies could currently be substantially underestimated. Adequately accounting for the damages of extreme weather events in policy evaluation may therefore help to prevent a critical lack of climate action.

Age-related change in cortical thickness in adolescents at clinical high risk for psychosis: a longitudinal study.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10-17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study.

BACKGROUND: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. METHODS: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5°â€ˆ× 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. FINDINGS: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. INTERPRETATION: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate. FUNDING: Australian Research Council and Australian National Health and Medical Research Council.

Understanding image-text relations and news values for multimodal news analysis.

The analysis of news dissemination is of utmost importance since the credibility of information and the identification of disinformation and misinformation affect society as a whole. Given the large amounts of news data published daily on the Web, the empirical analysis of news with regard to research questions and the detection of problematic news content on the Web require computational methods that work at scale. Today's online news are typically disseminated in a multimodal form, including various presentation modalities such as text, image, audio, and video. Recent developments in multimodal machine learning now make it possible to capture basic "descriptive" relations between modalities-such as correspondences between words and phrases, on the one hand, and corresponding visual depictions of the verbally expressed information on the other. Although such advances have enabled tremendous progress in tasks like image captioning, text-to-image generation and visual question answering, in domains such as news dissemination, there is a need to go further. In this paper, we introduce a novel framework for the computational analysis of multimodal news. We motivate a set of more complex image-text relations as well as multimodal news values based on real examples of news reports and consider their realization by computational approaches. To this end, we provide (a) an overview of existing literature from semiotics where detailed proposals have been made for taxonomies covering diverse image-text relations generalisable to any domain; (b) an overview of computational work that derives models of image-text relations from data; and (c) an overview of a particular class of news-centric attributes developed in journalism studies called news values. The result is a novel framework for multimodal news analysis that closes existing gaps in previous work while maintaining and combining the strengths of those accounts. We assess and discuss the elements of the framework with real-world examples and use cases, setting out research directions at the intersection of multimodal learning, multimodal analytics and computational social sciences that can benefit from our approach.

Massive Neonatal Arterial Ischemic Stroke.

BACKGROUND: Massive infarction in adults is a devastating entity characterized by signs of extreme swelling of the brain's parenchyma. We explored whether a similar entity exists in neonates, which we call massive neonatal arterial ischemic stroke (M-NAIS), and assess its potential clinical implications. METHODS: Prospective multicenter cohort study comprising 48 neonates with gestational age ≥35 weeks with middle cerebral artery (MCA) NAIS was performed. Diagnosis with magnetic resonance imaging (MRI) was performed within the first three days after symptom onset. The presence of signs of a space-occupying mass, such as brain midline shift and/or ventricular and/or extra-axial space collapse, was recorded. The volume of the infarct and brain midline shift were determined with semiautomatic procedures. Neurodevelopment was assessed at age 24 months. RESULTS: Fifteen (31%) neonates presented MRI signs of a space-occupying mass effect and were considered to have an M-NAIS. The relative volume (infarct volume/total brain volume) of the infarct was on average significantly greater in the M-NAIS subgroup (29% vs 4.9%, P < 0.001). Patients with M-NAIS consistently presented lesions involving the M1 arterial territory of the MCA and showed more apneic and tonic seizures, which had an earlier onset and lasted longer. Moderate to severe adverse neurodevelopmental outcomes were present in most M-NAIS cases (79% vs 6%, P < 0.001). CONCLUSIONS: M-NAIS appears to be a distinctive subtype of neonatal infarction, defined by characteristic neuroimaging signs. Neonates with M-NAIS frequently present a moderate to severe adverse outcome. Early M-NAIS identification would allow for prompt, specific rehabilitation interventions and would provide more accurate prognostic information to families.

Neurocognitive bases of self-monitoring of inner speech in hallucination prone individuals.

Verbal hallucinations in schizophrenia patients might be seen as internal verbal productions mistaken for perceptions as a result of over-salient inner speech and/or defective self-monitoring processes. Similar cognitive mechanisms might underpin verbal hallucination proneness in the general population. We investigated, in a non-clinical sample, the cerebral activity associated with verbal hallucinatory predisposition during false recognition of familiar words -assumed to stem from poor monitoring of inner speech-vs. uncommon words. Thirty-seven healthy participants underwent a verbal recognition task. High- and low-frequency words were presented outside the scanner. In the scanner, the participants were then required to recognize the target words among equivalent distractors. Results showed that verbal hallucination proneness was associated with higher rates of false recognition of high-frequency words. It was further associated with activation of language and decisional brain areas during false recognitions of low-, but not high-, frequency words, and with activation of a recollective brain area during correct recognitions of low-, but not high-, frequency words. The increased tendency to report familiar words as targets, along with a lack of activation of the language, recollective, and decisional brain areas necessary for their judgement, suggests failure in the self-monitoring of inner speech in verbal hallucination-prone individuals.

Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study.

BACKGROUND: Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior. METHODS: We analyzed 7,860 magnetic resonance images of children 9-11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also obtained several behavioral data (cognition, behavioral problems, prodromal psychotic experiences, prosociality, impulsivity) to explore the potential mediatory role of brain volumes on behavior. RESULTS: In the 7,860 children analyzed (median age = 9 years and 11 months; 49.9% female), whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the left lateral orbitofrontal cortex proved to be very robust to the addition of potentially confounding covariates, random selection of siblings, and splitting the sample in two. The volume of the left pars orbitalis and the left lateral orbitofrontal cortex appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist. CONCLUSIONS: Our findings suggest that breastfeeding is a relevant factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal cortex regions. This, in turn, may impact impulsive personality and mental health in early puberty.

Better insurance could effectively mitigate the increase in economic growth losses from U.S. hurricanes under global warming.

Global warming is likely to increase the proportion of intense hurricanes in the North Atlantic. Here, we analyze how this may affect economic growth. To this end, we introduce an event-based macroeconomic growth model that temporally resolves how growth depends on the heterogeneity of hurricane shocks. For the United States, we find that economic growth losses scale superlinearly with shock heterogeneity. We explain this by a disproportional increase of indirect losses with the magnitude of direct damage, which can lead to an incomplete recovery of the economy between consecutive intense landfall events. On the basis of two different methods to estimate the future frequency increase of intense hurricanes, we project annual growth losses to increase between 10 and 146% in a 2°C world compared to the period 1980-2014. Our modeling suggests that higher insurance coverage can compensate for this climate change-induced increase in growth losses.

Longitudinal Changes in Cortical Surface Area Associated With Transition to Psychosis in Adolescents at Clinical High Risk for the Disease.

OBJECTIVE: Identifying biomarkers of transition to psychosis in individuals at clinical high risk for psychosis (CHR-P) is essential to understanding the mechanisms underlying the disease. Although cross-sectional abnormalities in cortical surface area (CSA) have been demonstrated in individuals at CHR-P who transition to psychosis (CHR-P-T) compared with those who do not (CHR-P-NT), how CSA longitudinally develops remains unclear, especially in younger individuals. We set out to compare CSA in adolescents at CHR-P and healthy controls (HC) over 2 points in time. METHOD: A longitudinal multicenter study was performed in adolescents at CHR-P in comparison to HC and according to transition to psychosis. Magnetic resonance imaging scans were acquired at baseline, at 18-month follow-up, or at the time of transition. Images were pre-processed and hemisphere and regional CSA were computed using FreeSurfer. Between-group analyses were performed with linear mixed-effects models. RESULTS: A total of 313 scans (107 CHR-P and 102 HC) were included in the analysis. At 18 months, the rate of transition to psychosis in CHR-P was 23.4%. Adolescents at CHR-P-T presented greater age-related decrease in CSA in the left parietal and occipital lobes compared with HC, and in the bilateral parietal lobe and right frontal lobe relative to CHR-P-NT. These results were not influenced by antipsychotic treatment, cannabis use, or intelligence quotient (IQ). CONCLUSION: Adolescents at CHR-P that developed a psychotic disorder presented different developmental trajectories of CSA relative to those who did not. A relatively greater decrease in CSA in the parietal and frontal lobes may index clinical transition to psychosis in adolescents at CHR-P.

Manipulating base quality scores enables variant calling from bisulfite sequencing alignments using conventional bayesian approaches.

BACKGROUND: Calling germline SNP variants from bisulfite-converted sequencing data poses a challenge for conventional software, which have no inherent capability to dissociate true polymorphisms from artificial mutations induced by the chemical treatment. Nevertheless, SNP data is desirable both for genotyping and to understand the DNA methylome in the context of the genetic background. The confounding effect of bisulfite conversion however can be conceptually resolved by observing differences in allele counts on a per-strand basis, whereby artificial mutations are reflected by non-complementary base pairs. RESULTS: Herein, we present a computational pre-processing approach for adapting sequence alignment data, thus indirectly enabling downstream analysis on a per-strand basis using conventional variant calling software such as GATK or Freebayes. In comparison to specialised tools, the method represents a marked improvement in precision-sensitivity based on high-quality, published benchmark datasets for both human and model plant variants. CONCLUSION: The presented "double-masking" procedure represents an open source, easy-to-use method to facilitate accurate variant calling using conventional software, thus negating any dependency on specialised tools and mitigating the need to generate additional, conventional sequencing libraries alongside bisulfite sequencing experiments. The method is available at https://github.com/bio15anu/revelio and an implementation with Freebayes is available at https://github.com/EpiDiverse/SNP.

Volumetric study of brain MRI in a cohort of patients with neurotransmitter disorders.

PURPOSE: Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders. METHODS: Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age. RESULTS: Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life. CONCLUSION: Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

The Search as Learning Spaceship: Toward a Comprehensive Model of Psychological and Technological Facets of Search as Learning.

Using a Web search engine is one of today's most frequent activities. Exploratory search activities which are carried out in order to gain knowledge are conceptualized and denoted as Search as Learning (SAL). In this paper, we introduce a novel framework model which incorporates the perspective of both psychology and computer science to describe the search as learning process by reviewing recent literature. The main entities of the model are the learner who is surrounded by a specific learning context, the interface that mediates between the learner and the information environment, the information retrieval (IR) backend which manages the processes between the interface and the set of Web resources, that is, the collective Web knowledge represented in resources of different modalities. At first, we provide an overview of the current state of the art with regard to the five main entities of our model, before we outline areas of future research to improve our understanding of search as learning processes.

Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates.

Thlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high-quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe non-coding RNAs, pseudogenes and transposable elements, and highlight tissue-specific expression and methylation patterns. Resequencing of forty wild accessions provided insights into genome-wide genetic variation, and QTL regions were identified for a seedling colour phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae.

Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study.

OBJECTIVE: In contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age. DESIGN: Prospective observational multicentre study. SETTING: Six paediatric university hospitals in Spain. PARTICIPANTS: We included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age. MAIN OUTCOME MEASURES: We analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume. RESULTS: We found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012). CONCLUSIONS: The identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

EpiDiverse Toolkit: a pipeline suite for the analysis of bisulfite sequencing data in ecological plant epigenetics.

The expanding scope and scale of next generation sequencing experiments in ecological plant epigenetics brings new challenges for computational analysis. Existing tools built for model data may not address the needs of users looking to apply these techniques to non-model species, particularly on a population or community level. Here we present a toolkit suitable for plant ecologists working with whole genome bisulfite sequencing; it includes pipelines for mapping, the calling of methylation values and differential methylation between groups, epigenome-wide association studies, and a novel implementation for both variant calling and discriminating between genetic and epigenetic variation.

Effects of climate change on combined labour productivity and supply: an empirical, multi-model study.

BACKGROUND: Although effects on labour is one of the most tangible and attributable climate impact, our quantification of these effects is insufficient and based on weak methodologies. Partly, this gap is due to the inability to resolve different impact channels, such as changes in time allocation (labour supply) and slowdown of work (labour productivity). Explicitly resolving those in a multi-model inter-comparison framework can help to improve estimates of the effects of climate change on labour effectiveness. METHODS: In this empirical, multi-model study, we used a large collection of micro-survey data aggregated to subnational regions across the world to estimate new, robust global and regional temperature and wet-bulb globe temperature exposure-response functions (ERFs) for labour supply. We then assessed the uncertainty in existing labour productivity response functions and derived an augmented mean function. Finally, we combined these two dimensions of labour into a single compound metric (effective labour effects). This combined measure allowed us to estimate the effect of future climate change on both the number of hours worked and on the productivity of workers during their working hours under 1·5°C, 2·0°C, and 3·0°C of global warming. We separately analysed low-exposure (indoors or outdoors in the shade) and high-exposure (outdoor in the sun) sectors. FINDINGS: We found differentiated empirical regional and sectoral ERF's for labour supply. Current climate conditions already negatively affect labour effectiveness, particularly in tropical countries. Future climate change will reduce global total labour in the low-exposure sectors by 18 percentage points (range -48·8 to 5·3) under a scenario of 3·0°C warming (24·8 percentage points in the high-exposure sectors). The reductions will be 25·9 percentage points (-48·8 to 2·7) in Africa, 18·6 percentage points (-33·6 to 5·3) in Asia, and 10·4 percentage points (-35·0 to 2·6) in the Americas in the low-exposure sectors. These regional effects are projected to be substantially higher for labour outdoors in full sunlight compared with indoors (or outdoors in the shade) with the average reductions in total labour projected to be 32·8 percentage points (-66·3 to 1·6) in Africa, 25·0 percentage points (-66·3 to 7·0) in Asia, and 16·7 percentage points (-45·5 to 4·4) in the Americas. INTERPRETATION: Both labour supply and productivity are projected to decrease under future climate change in most parts of the world, and particularly in tropical regions. Parts of sub-Saharan Africa, south Asia, and southeast Asia are at highest risk under future warming scenarios. The heterogeneous regional response functions suggest that it is necessary to move away from one-size-fits-all response functions to investigate the climate effect on labour. Our findings imply income and distributional consequences in terms of increased inequality and poverty, especially in low-income countries, where the labour effects are projected to be high. FUNDING: COST (European Cooperation in Science and Technology).