The ability to transfer knowledge across tasks and generalize to novel ones is an important hallmark of human intelligence. Yet not much is known about human multitask reinforcement learning. We study participants' behaviour in a two-step decision-making task with multiple features and changing reward functions. We compare their behaviour with two algorithms for multitask reinforcement learning, one that maps previous policies and encountered features to new reward functions and one that approximates value functions across tasks, as well as to standard model-based and model-free algorithms. Across three exploratory experiments and a large preregistered confirmatory experiment, our results provide evidence that participants who are able to learn the task use a strategy that maps previously learned policies to novel scenarios. These results enrich our understanding of human reinforcement learning in complex environments with changing task demands.Previous research points to the heritability of risk-taking behaviour. MK-0752 supplier However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18 months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD.The aim of this study was to investigate the presence of preoperative DVT following spinal fracture and the association between the presence of DVT and risk factors. Ultrasonography and blood analyses were performed preoperatively in patients diagnosed with spinal fracture between October 2014 and December 2018. Univariate analyses were performed on the data of demographics, comorbidities, location of injury, spinal cord injury (SCI) grading and laboratory biomarkers. The receiver operating characteristic (ROC) curve analysis was employed to obtain the optimal D-dimer cut-off value for diagnosis. In total, 2432 patients with spinal fractures were included, among whom 108 (4.4%) patients had preoperative DVTs. The average interval between fracture and initial diagnosis of DVT was 4.7 days (median, 2 days), ranging from 0 to 20 days; 78 (72.2%) were diagnosed within 7 days after injury and 67 (62.0%) within 3 days; 19 (17.5%) patients had proximal vein involved and 89 (82.4%) presented in distal veins. Multivariate logistic regression suggested six risk factors independently correlated to DVT, including delay to DUS (in each day) (odds ratio [OR] = 1.11), ASA class III-IV (OR = 2.36), ASIA grade (A/B) (OR = 2.36), ALB  1.08 µg/ml (OR = 2.49).DNA mismatch repair (MMR) relies on MutS and MutL ATPases for mismatch recognition and strand-specific nuclease recruitment to remove mispaired bases in daughter strands. However, whether the MutS-MutL complex coordinates MMR by ATP-dependent sliding on DNA or protein-protein interactions between the mismatch and strand discrimination signal is ambiguous. Using functional MMR assays and systems preventing proteins from sliding, we show that sliding of human MutSα is required not for MMR initiation, but for final mismatch removal. MutSα recruits MutLα to form a mismatch-bound complex, which initiates MMR by nicking the daughter strand 5' to the mismatch. Exonuclease 1 (Exo1) is then recruited to the nick and conducts 5' → 3' excision. ATP-dependent MutSα dissociation from the mismatch is necessary for Exo1 to remove the mispaired base when the excision reaches the mismatch. Therefore, our study has resolved a long-standing puzzle, and provided new insights into the mechanism of MMR initiation and mispair removal.Compelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. COMP deficiency results in activation of AT1a-β-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion.