Search

Background The MINDMAP project implemented a multinational data infrastructure to investigate the direct and interactive effects of urban environments and individual determinants of mental well-being and cognitive function in ageing populations. Using a rigorous process involving multiple teams of experts, longitudinal data from six cohort studies were harmonised to serve MINDMAP objectives. This article documents the retrospective data harmonisation process achieved based on the Maelstrom Research approach and provides a descriptive analysis of the harmonised data generated. Methods A list of core variables (the DataSchema) to be generated across cohorts was first defined, and the potential for cohort-specific data sets to generate the DataSchema variables was assessed. Where relevant, algorithms were developed to process cohort-specific data into DataSchema format, and information to be provided to data users was documented. Procedures and harmonisation decisions were thoroughly documented. Results The MINDMAP DataSchema (v2.0, April 2020) comprised a total of 2841 variables (993 on individual determinants and outcomes, 1848 on environmental exposures) distributed across up to seven data collection events. The harmonised data set included 220 621 participants from six cohorts (10 subpopulations). Harmonisation potential, participant distributions and missing values varied across data sets and variable domains. Conclusion The MINDMAP project implemented a collaborative and transparent process to generate a rich integrated data set for research in ageing, mental well-being and the urban environment. The harmonised data set supports a range of research activities and will continue to be updated to serve ongoing and future MINDMAP research needs.

Background Loneliness is associated with several adverse mental and physical health outcomes in older adults. Previous studies have shown that a variety of individual-level and perceived area-level characteristics are associated with loneliness. This study examined the associations of objectively measured social and physical neighbourhood characteristics with loneliness. Methods We used cross-sectional data from 1959 older adults (63–98 years) who participated in the Longitudinal Ageing Study Amsterdam (LASA; wave 2011/12) and the Health and Living Conditions of the Population of Eindhoven and Surroundings study (GLOBE; wave 2014) in the Netherlands. Study-specific loneliness scores were harmonised across both cohort studies and divided into tertiles denoting low, medium and high levels of loneliness. Objectively measured neighbourhood characteristics, including area-level percentages of low educated residents, social security beneficiaries and unoccupied dwellings, average income, crime levels and land use mix, were linked to individual-level data. Multinomial logistic regression analyses were conducted to examine the associations of interest. Results There was no statistical evidence for an association of the included neighbourhood characteristics with loneliness. Although not statistically significant, the observed associations suggested that participants living in neighbourhoods with more heterogeneous land use mix were less likely to have a medium and high level of loneliness than those living in more homogeneous neighbourhoods in terms of land use mix (ORmedium=0.54, 95% CI=0.18–1.67; ORhigh=0.67, 95% CI=0.21–2.11). Conclusion The results indicate that the included objectively measured social and physical neighbourhood characteristics are not associated with loneliness in old age.

Background and purposeWe aimed to identify the best definition of early neurological improvement (ENI) at 2 and 24 hours after mechanical thrombectomy (MT) and determine its ability to predict a good functional outcome at 3 months.MethodsThis retrospective analysis was based on a prospectively collected registry of patients treated by MT for ischemic stroke from May 2010 to March 2017. We included patients treated with stent-retrievers with National Institute of Health Stroke Scale (NIHSS) score before treatment and at 2 and/or 24 hours after treatment and modified Rankin Score (mRS) at 3 months. Receiver operating characteristic curve analysis was performed to estimate optimal thresholds for ENI at 2 and 24 hours. The relationship between optimal ENI definitions and good outcome at 3 months (mRS 0–2) was assessed by logistic regression.ResultsThe analysis included 246 patients. At 2 hours, the optimal threshold to predict a good outcome at 3 months was improvementin the NIHSS score of >1 point (AUC 0.83,95% CI 0.77 to 0.87), with sensitivity and specificity 78.3% (62.2–85.7%) and 84.6% (77.2–90.3%), respectively, and OR 12.67 (95% CI 4.69 to 31.10, p4 points (AUC 0.93, 95% CI 0.89 to 0.96), with sensitivity and specificity 93.8% (87.7–97.5%) and 83.2% (75.7–89.2%), respectively, and OR 391.32 (95% CI 44.43 to 3448.35, pConclusionsENI 24 hours after thrombectomy appears to be a straightforward surrogate of long-term endpoints and may have value in future research.

Whether to withhold mechanical thrombectomy when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is undetermined. Our aim was to identify markers that will help to select patients with large DWI lesions [DWI-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) ≤ 5] that may benefit from thrombectomy.From May 2010 to November 2016, 82 acute ischaemic stroke patients with DWI-ASPECTS ≤5 (43 men, 64.6 ± 14.4 years, National Institutes of Health Stroke Scale 18.4 ± 5.4) treated with state-of-the-art mechanical thrombectomy were studied. Thrombectomy alone was performed in 28 (34%) and bridging therapy in 54 (66%) patients. Recanalization was defined as a thrombolysis in cerebral infarction score 2B-3 and significant hemorrhagic transformation as parenchymal haematoma type 2 (European Cooperative Acute Stroke Study 3 classification). Pretreatment variables were compared between patients with a good (modified Rankin Scale 0-2) and a poor (modified Rankin Scale 3-6) neurological outcome at 3 months.Overall, 28 patients (34%) achieved good neurological outcome at 3 months. Recanalizers were significantly more likely to achieve good outcome (61% vs. 7.3%, P0.0001), had lower mortality (24% vs. 49%, P = 0.03) and similar rates of parenchymal haematoma type 2 (9.8% vs. 7.3%, P = 1) compared to non-recanalizers. Regression modelling identified DWI-ASPECTS2 [odds ratio (OR) 6.93; 95% confidence interval (CI) 1.05-45.76, P = 0.04), glycaemia ≤6.8 mmol/l (OR 4.05; 95% CI 1.09-15.0, P = 0.03) and thrombolysis (OR 3.67; 95% CI 1.04-12.9, P = 0.04) as independent predictors of good neurological outcome.In patients with DWI-ASPECTS ≤5, two-thirds of patients experienced good neurological outcome when recanalized by state-of-the-art thrombectomy, whilst only one in 14 non-recanalizers achieved similar outcomes. Pretreatment markers of good neurological outcomes were DWI-ASPECTS2, intravenous thrombolysis and glycaemia ≤6.8 mmol/l.

New COVID-19 related instruments are being rapidly developed around the world to collect patient- and population-based information Heterogeneity between instru

The cuticle is an essential diffusion barrier on aerial surfaces of land plants whose structural component is the polyester cutin. The PERMEABLE CUTICLE1/ABCG32 (PEC1) transporter is involved in plant cuticle formation in Arabidopsis. The gpat6 pec1 and gpat4 gapt8 pec1 double and triple mutants are characterized. Their PEC1-specific contributions to aliphatic cutin composition and cuticle formation during plant development are revealed by gas chromatography/mass spectrometry and Fourier-transform infrared spectroscopy. The composition of cutin changes during rosette leaf expansion in Arabidopsis. C16:0 monomers are in higher abundance in expanding than in fully expanded leaves. The atypical cutin monomer C18:2 dicarboxylic acid is more prominent in fully expanded leaves. Findings point to differences in the regulation of several pathways of cutin precursor synthesis. PEC1 plays an essential role during expansion of the rosette leaf cuticle. The reduction of C16 monomers in the pec1 mutant during leaf expansion is unlikely to cause permeability of the leaf cuticle because the gpat6 mutant with even fewer C16:0 monomers forms a functional rosette leaf cuticle at all stages of development. PEC1/ABCG32 transport activity affects cutin composition and cuticle structure in a specific and non-redundant fashion.

Introduction L’indication de la thrombectomie mecanique dans les lesions ischemiques depassant un certain volume sur la sequence de diffusion reste indeterminee. Nous avons cherche a identifier des facteurs qui aideraient a selectionner les patients ayant des lesions ischemiques etendues sur la sequence de diffusion (Diffusion Weighted Imaging-Alberta Stroke Program Early CT Score, DWI-ASPECTS≤5) et qui pourraient beneficier d’une thrombectomie. Materiels et methodes De mai 2010 a novembre 2016, nous avons etudie 82 patients atteints d’accidents vasculaires cerebraux (AVC) ischemiques aigus avec un score DWI-ASPECTS≤5 (43 hommes, 64,6 ± 14,4 ans, NIHSS (National Institutes of Health Stroke Scale) 18,4 ± 5,4) et traites par thrombectomie mecanique. La thrombectomie seule a ete effectuee chez 28 patients (34 %) et en association avec une thrombolyse intraveineuse (TIV) chez 54 patients (66 %). La recanalisation a ete definie par un score TICI (thrombolysis in cerebral infarction) 2B-3 et une transformation hemorragique significative par un hematome intraparenchymateux de type 2 (European Cooperative Acute Stroke Study 3 classification). Les variables pre-traitement ont ete comparees entre les patients ayant eu un resultat neurologique favorable a 3 mois (modified Rankin Scale-mRS 0-2) et ceux avec un resultat defavorable (mRS 3-6). Resultats Vingt-huit patients (34 %) ont obtenu un resultat neurologique favorable a 3 mois. Les patients recanalises avaient une probabilite d’obtenir un bon resultat clinique significativement plus eleve (61 % contre 7,3 %, p 2 (OR 6,93 ; 95 % CI [1,05–45,76], p = 0,04), une glycemie ≤ 6,8 mmol/L (OR 4,05 ; 95 % CI [1,09–15,0], p = 0,03) et la TIV (OR 3,67 ; 95 % CI [1,04–12,9], p = 0,04) comme facteurs predictifs independants de resultat neurologique favorable. Conclusion Parmi les patients avec un score DWI-ASPECTS≤5, 2/3 ont obtenu un resultat neurologique favorable lorsqu’ils ont ete recanalises par une thrombectomie, contre seulement 1/14 des non-recanalises. Les facteurs pre-traitement de bon resultat neurologique etaient un score DWI-ASPECTS > 2, la TIV et une glycemie ≤ 6,8 mmol/L.

Although the multilayered structure of the plant cuticle was discovered many years ago, the molecular basis of its formation and the functional relevance of the layers are not understood. Here, we present the permeable cuticle1 (pec1) mutant of Arabidopsis thaliana, which displays features associated with a highly permeable cuticle in several organs. In pec1 flowers, typical cutin monomers, such as ω- hydroxylated fatty acids and 10,16-dihydroxypalmitate, are reduced to 40% of wild-type levels and are accompanied by the appearance of lipidic inclusions within the epidermal cell. The cuticular layer of the cell wall, rather than the cuticle proper, is structurally altered in pec1 petals. Therefore, a significant role for the formation of the diffusion barrier in petals can be attributed to this layer. Thus, pec1 defines a new class of mutants. The phenotypes of the pec1 mutant are caused by the knockout of ATP BINDING CASSETTEG32 (ABCG32), an ABC transporter from the PLEIOTROPIC DRUG RESISTANCE family that is localized at the plasma membrane of epidermal cells in a polar manner toward the surface of the organs. Our results suggest that ABCG32 is involved in the formation of the cuticular layer of the cell wall, most likely by exporting particular cutin precursors from the epidermal cell.

Introduction Le but etait d’identifier la meilleure definition de l’amelioration neurologique precoce (ANP) a 2 h et 24 h apres thrombectomie et de determiner sa capacite a predire un devenir fonctionnel a 3 mois. Materiel et methodes Analyse retrospective a partir d’un registre monocentrique de patients traites par thrombectomie mecanique entre mai 2010 et mars 2017. Etaient inclus pour analyse les patients traites par stent-retriever , avec un National Institute of Health Stroke Scale (NIHSS) evalue a 2 h et/ou 24 h apres traitement et un Modified Rankin Score (mRS) evalue a 3 mois. Les donnees demographiques, cliniques et d’imagerie etaient recueillies. Les seuils optimaux d’ANP a 2 h et 24 h ont ete estimes par l’analyse des courbes ROC. La relation entre les definitions optimales d’ANP et le devenir favorable a 3 mois a ete evaluee a l’aide de regressions logistiques. Resultats Au total, 246 patients ont ete inclus. A 2 h, le seuil optimal pour predire une bonne evolution neurologique a 3 mois etait une amelioration du score NIHSS > 1 point (AUC 0,83 [IC95 % : 0,77–0,87]) avec une sensibilite de 78,3 % (62,2–85,7 %), une specificite de 84,6 % (77,2–90,3 %) et un OR de 4,23 (IC95 % : 1,39–12,88, p = 0,01). A 24 h, il s’agissait d’une amelioration du score NIHSS > 4 points (AUC : 0,93 [IC95 % : 0,89–0,96]) avec une sensibilite de 93,8 % (87,7–97,5 %), une specificite de 83,2 % (75,7–89,2 %) et un OR de 81,47 (IC95 % : 15,95–415,42, p Conclusion L’ANP a 24 h apres thrombectomie apparait etre un marqueur pronostique simple et fiable du devenir a long terme et pourrait servir de critere de jugement dans de futures etudes.

International audience; Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancers (NSCLC) account for 3% to 7% of all NSCLC and require a standard treatment by crizotinib. However, crizotinib resistance is frequent within the first 12 months of treatment. Ceritinib is a novel tyrosine kinase inhibitor of ALK recently introduced in France for metastatic or locally advanced crizotinib-resistant ALK NSCLC. We report the first use of ceritinib in our institution with a spectacular tumoral response after only 3 months of treatment. This case demonstrates the major role of F-FDG PET/CT for monitoring the effectiveness of this new treatment.