Explore the vast range of titles available.

Theories of human neurobehavioral development suggest executive functions mature from childhood through adolescence, underlying adolescent risk-taking and the emergence of psychopathology. Investigations with relatively small datasets or narrow subsets of measures have identified general executive function development, but the specific maturational timing and independence of potential executive function subcomponents remain unknown. Integrating four independent datasets (N = 10,766; 8–35 years old) with twenty-three measures from seventeen tasks, we provide a precise charting, multi-assessment investigation, and replication of executive function development from adolescence to adulthood. Across assessments and datasets, executive functions follow a canonical non-linear trajectory, with rapid and statistically significant development in late childhood to mid-adolescence (10–15 years old), before stabilizing to adult-levels in late adolescence (18–20 years old). Age effects are well captured by domain-general processes that generate reproducible developmental templates across assessments and datasets. Results provide a canonical trajectory of executive function maturation that demarcates the boundaries of adolescence and can be integrated into future studies. Goal-directed cognition (executive function) is thought to develop through adolescence. Here, the authors find evidence across multiple datasets and measures that executive function develops until 18–20 years old.

EUREGHA's vision is to ensure that the local and regional perspective is represented in EU health policy because local and regional authorities are the natural interface between citizens and European institutions, being the bridging bodies between policies and practices and the closest organizations to the concept of communities. We are the only European network prioritizing the representation of local and regional health authorities at EU level, as they fulfil a key role in improving efficiency, quality, and accessibility of healthcare systems and services. EUREGHA understands their specific needs and works tirelessly to represent regional and local health authorities in EU health policy, to amplify their voices as a means to improve European public health and healthcare. Through advocacy, policy monitoring, profile promotion, partnerships, and project development, EUREGHA facilitates and promotes collaboration between its members, EU institutions, pan-European health networks and other healthcare stakeholders. Network activities and projects are implemented upon a strategic background of “ways to make things happen” such as value based healthcare, smart specialization strategies and skills for innovation and digital transformation - on one side - and along thematic and field objectives such as cross-border healthcare, cancer, obesity, mental health and ageing - on the other side. Lower Austria is a long-standing member and Vice-Chair of EUREGHA.

EUREGHA's vision is to ensure that the local and regional perspective is represented in EU health policy because local and regional authorities are the natural interface between citizens and European institutions, being the bridging bodies between policies and practices and the closest organizations to the concept of communities. We are the only European network prioritizing the representation of local and regional health authorities at EU level, as they fulfil a key role in improving efficiency, quality, and accessibility of healthcare systems and services. EUREGHA understands their specific needs and works tirelessly to represent regional and local health authorities in EU health policy, to amplify their voices as a means to improve European public health and healthcare. Through advocacy, policy monitoring, profile promotion, partnerships, and project development, EUREGHA facilitates and promotes collaboration between its members, EU institutions, pan-European health networks and other healthcare stakeholders. Network activities and projects are implemented upon a strategic background of “ways to make things happen” such as value based healthcare, smart specialization strategies and skills for innovation and digital transformation - on one side - and along thematic and field objectives such as cross-border healthcare, cancer, obesity, mental health and ageing - on the other side. Lower Austria is a long-standing member and Vice-Chair of EUREGHA.

PurposeThe aim of this paper is to assess whether the current European target to increase the areas under organic farming to 25% by 2030 is attainable and whether the simple increase in areas under organic farming may be sufficient to improve the sustainability of European agriculture.Design/methodology/approachThe analysis has been carried out through a simple data processing related to areas under organic farming, for the period 2012–2020 (Eurostat database), in order to highlight the trends of areas under organic farming and to verify whether the annual average change rates may be compatible with the stated target.FindingsThe analysis showed that organic farming has a productive weight not corresponding to the amount on the total of the areas under cultivation and a small impact on the total of food consumption. It is a plausible hypothesis, the one that shows the increase in areas under organic farming will engage forms of agriculture and farms that, already, are more sustainable, so the achievement of 25% target will not particularly impact the European potential productive and the less environmental sustainable forms of agriculture.Originality/valueThis paper contributes to the debate, involving scientific community, policy maker and civil society, about the real contribution of organic farming to sustainability, and it will be developed in future research.

Resolving single-crystal structures of two-dimensional covalent organic frameworks (2D COFs) is a great challenge, hindered in part by limited strategies for growing high-quality crystals. A better understanding of the growth mechanism facilitates development of methods to grow high-quality 2D COF single crystals. Here, we take a different perspective to explore the 2D COF growth process by tracing growth intermediates. We discover two different growth mechanisms, nucleation and self-healing, in which self-assembly and pre-arrangement of monomers and oligomers are important factors for obtaining highly crystalline 2D COFs. These findings enable us to grow micron-sized 2D single crystalline COF Py-1P. The crystal structure of Py-1P is successfully characterized by three-dimensional electron diffraction (3DED), which confirms that Py-1P does, in part, adopt the widely predicted AA stacking structure. In addition, we find the majority of Py-1P crystals (>90%) have a previously unknown structure, containing 6 stacking layers within one unit cell. Resolving single-crystal structures of two-dimensional covalent organic frameworks (2D COFs) is a great challenge. Here, the authors identify two different growth mechanisms of COFs, enabling the growth and structure determination of micron-sized 2D single-crystalline COFs.

Covalent organic frameworks (COFs) are emerging crystalline porous polymers, showing great potential for applications but lacking gas-triggered flexibility. Atropisomerism was experimentally discovered in 1922 but has rarely been found in crystals with infinite framework structures. Here we report atropisomerism in COF single crystals. The obtained COF atropisomers, namely COF-320 and COF-320-A, have identical chemical and interpenetrated structures but differ in the spatial arrangement of repeating units. In contrast to the rigid COF-320 structure, its atropisomer (COF-320-A) exhibits unconventional gas sorption behaviours with one or more sorption steps in isotherms at different temperatures. Single-crystal structures determined from continuous rotation electron diffraction and in situ powder X-ray diffraction demonstrate that these adsorption steps originate from internal pore expansion with or without changing the crystal space group. COF-320-A recognizes different gases by expanding its internal pores continuously (crystal-to-amorphous transition) or discontinuously (crystal-to-crystal transition) or having mixed transition styles, distinguishing COF-320-A from existing soft/flexible porous crystals. These findings extend atropisomerism from molecules to crystals and propel COFs into the covalently linked soft porous crystal regime, further advancing applications of soft porous crystals in gas sorption, separation and storage.Soft porous crystals combine high crystallinity with structural transformability, potentially enabling applications. Here, an atropisomeric covalent organic framework is reported, which demonstrates different structural transformations upon exposure to different gases.

Adolescence is increasingly viewed as a sensitive period in the development of substance use disorders (SUDs). Neurodevelopmental ‘dual-risk’ theories suggest adolescent vulnerability to problematic substance use is driven by an overactive reward drive mediated by the striatum, and poor cognitive control mediated by the prefrontal cortex. To this end, there has been a growing number of neuroimaging studies examining cognitive and affective neural systems during adolescence for markers of vulnerability to problematic substance use. Here, we perform a coordinate-based meta-analysis on this emerging literature. Twenty-two task-based voxelwise fMRI studies with activation differences associated with substance use vulnerability, representative of approximately 1092 subjects, were identified through a systematic literature search (PubMed, Scopus) and coordinates of activation differences (N ​= ​190) were extracted. Adolescents were defined as ‘at-risk’ for problematic substance use based on a family history of SUD or through prospective prediction of substance use initiation or escalation. Multilevel kernel density analysis was used to identify the most consistent brain regions associated with adolescent substance use vulnerability. Across the included studies, substance use vulnerability was most reliably associated with activation differences in the striatum, where at-risk adolescents had hyper-activation in the dorsal subdivision (putamen). Follow-up analyses suggested striatal differences were driven by tasks sharing a motivational and/or reward component (e.g., monetary incentive) and common across subgroups of substance use risk (family history and prospective prediction studies). Analyses examining the role of psychiatric comorbidity revealed striatal activation differences were significantly more common in samples whose definition of substance use risk included cooccurring externalizing psychopathology. Furthermore, substance use risk meta-analytic results were no longer significant when excluding these studies, although this may reflect limitations in statistical power. No significant activation differences were observed in prefrontal cortex in any analysis. These results suggest striatal dysfunction, rather than prefrontal, may be a more primary neural feature of adolescent vulnerability to problematic substance use, possibly through a dimension of individual variability shared with externalizing psychopathology. However, our systematic literature search confirms this is still an emerging field. More studies, increased data sharing, and further quantitative integration are necessary for a comprehensive understanding of the neuroimaging markers of adolescent substance use risk. •Systematic literature search of fMRI studies of youth at risk for substance use disorders.•Coordinates of activation differences were integrated from twenty-two studies.•Substance use risk was most associated with activation differences in the striatum.•Striatal differences were more common in studies including externalizing disorders.•Larger studies and increased data sharing are necessary.

BackgroundBone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy.MethodsPretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM.ResultsCohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p <  0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p <  0.0001; Cohort B: 2.7 versus 5.2 months, p <  0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p <  0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78).ConclusionsBoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

The development of the striatum dopamine (DA) system through human adolescence, a time of increased sensation seeking and vulnerability to the emergence of psychopathology, has been difficult to study due to pediatric restrictions on direct in vivo assessments of DA. Here, we applied neuroimaging in a longitudinal sample of n = 146 participants aged 12–30. R2′, an MR measure of tissue iron which co-localizes with DA vesicles and is necessary for DA synthesis, was assessed across the sample. In the 18–30 year-olds (n = 79) we also performed PET using [11C]dihydrotetrabenazine (DTBZ), a measure of presynaptic vesicular DA storage, and [11C]raclopride (RAC), an indicator of D2/D3 receptor availability. We observed decreases in D2/D3 receptor availability with age, while presynaptic vesicular DA storage (as measured by DTBZ), which was significantly associated with R2′ (standardized coefficient = 0.29, 95% CI = [0.11, 0.48]), was developmentally stable by age 18. Our results provide new evidence for maturational specialization of the striatal DA system through adolescence. How the human dopamine system changes during adolescence is still unclear. Here, the authors combine PET and quantitative MRI measures to show that dopamine D2/D3 receptor availability decreases with age while presynaptic dopamine vesicular storage was developmentally stable by age 18

•Successful reward learning is associated with elevated striatal dopamine release.•Improvements are driven by the reliable use of task-optimal learning rates.•Optimal learning is supported by cortical activation during reward expectation. Converging evidence from both human neuroimaging and animal studies has supported a model of mesolimbic processing underlying reward learning behaviors, based on the computation of reward prediction errors. However, competing evidence supports human dopamine signaling in the basal ganglia as also contributing to the generation of higher order learning heuristics. Here, we present data from a large (N = 81, 18–30yo), multi-modal neuroimaging study using simultaneously acquired task fMRI, affording temporal resolution of reward system function, and PET imaging with [11C]Raclopride (RAC), assessing striatal dopamine (DA) D2/3 receptor binding, during performance of a probabilistic reward learning task. Both fMRI activation and PET DA measures showed ventral striatum involvement for signaling rewards. However, greater DA release was uniquely associated with learning strategies (i.e., learning rates) that were more task-optimal within the best fitting reinforcement learning model. This DA response was associated with BOLD activation of a network of regions including anterior cingulate cortex, medial prefrontal cortex, thalamus and posterior parietal cortex, primarily during expectation, rather than prediction error, task epochs. Together, these data provide novel, human in vivo evidence that striatal dopaminergic signaling interacts with a network of cortical regions to generate task-optimal learning strategies, rather than representing reward outcomes in isolation.