Tectonic significance of Late Paleozoic deformation in the Cape George Peninsula, Antigonish Highlands, Nova Scotia

Late Paleozoic deformation of the Cape George Peninsula, Antigonish Highlands, Nova Scotia, provides information on post-accretionary fault movements associated with waning stages of Appalachian orogenic activity. Anomalously intense brittle to ductile deformation of the low-grade Late Paleozoic rocks of the peninsula occurred along east-west shear zones in a ca. 4 km-wide belt bounded by the NE-trending Hollow and Greendale faults. Deformation adjacent to, and between, these two faults resulted in brecciation, folding and thrusting, the development of slickensides on major dislocation surfaces, the local development of S-C fabrics and stretching lineations defined by elongate pebbles, and/or the production of extensional fractures and veins. The data suggest dextral and subordinate thrust components of movement along the east-west shear zones. Deformation is attributed to dextrally oblique compression between the bounding Hollow and Greendale faults along which significant reverse displacements are proposed on the basis of fault geometry and kinematics. The Cape George Peninsula is interpreted as a "popup" structure between these back-to-back oblique-slip reverse faults and is considered to occupy a strongly transpressive step-over zone between them. The east-west shear zones, which record dextral transpressive motion and steepen towards the north in a positive half-flower structure configuration, are parallel to Reidel R-shears of the shear fracture array and are interpreted to be transfer faults within the step-over zone along which oblique slip with dextral and reverse components of motion was transferred from the Hollow Fault to the Greendale Fault. Development of the regional stress regime required by these fault kinematics is consistent with coeval post-accretionary dextral motion between the Meguma and Avalon composite terranes along the east-west Cobcquid-Chedabucto fault system. RÉSUMÉ La déformation du Paléozoique tandif de la péninsule dc Cap George, dans les hautes terres d'Antigonish en Nouvelle-Écosse, fournit des informations sur les mouvements de failles post-accrétionaires associés aux stades terminaux de l'activité orogénique appalachienne. Une déformation fragile à ductile anormalement intense des roches du Paléozoique supérieur de faible grade s'est produite le long de zones de cisaillement est-ouest dans une ceinture d'environ 4 km de largeur limited par les failles de Hollow et de Greendale d'orientation nord-est. La déformation adjacente et entre ces failles a résulté en de la bélchification, du plissement et du chevauchement, le développement de slickensides sur des surfaces de dislocation majeures, le développement local de fabriques C-S et de linéations d'étirement définies par des cailloux allongés, et/ou la production de fractures et de veines d'extension. Les données suggèrent des composantes de mouvement dextres et, dans une moindre mesure, de chevauchement le long des zones de cisaillement est-ouest. La déformation est attributée à une compression dextre oblique entre les failles limitrophes de Hollow et de Greendale le long desquelles des deplacements inverses importants sont proposés sur la base de la géométrie et de la cinémalique des failles. La péninsule de Cap George est interprét6e comme une structure d'extrusion verticale entre ces deux failles obliques a mouvement inverse, dos à dos, et est considérée comme occupant une zone de recouvrement fortement transpressive entre elles. Les zones de cisaillement est-ouest, qui montrent un mouvement de transpression dextre et deviennent plus abruples vers le nord en une configuration de demie "flower structure" positive, sont parallèles aux riedels synlhétiques du réseau de fractures de cisaillement et sont interprétées comme étant des failles de transfert à l'intérieur de la zone de transfert suivant lesquelles un mouvement oblique avec des composantes de mouvement dextre et inverse furent transferées de la faille de Hollow à la faille de Greendale. Le développement du régime de contrainte régional requis par ces cindmatiques de failles est en accord avec un mouvement post-accrétionaire dextre entre les terrains de Meguma et d'Avalon composite le long du systeme de faille est-ouest de Cobcquid-Chedabucto. [Traduit par la rédaction

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

Author Correction: The challenge of mapping the human connectome based on diffusion tractography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

A novel Alzheimer disease locus located near the gene encoding tau protein

APOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Solar Weather Event Modelling and Prediction

Key drivers of solar weather and mid-term solar weather are reviewed by considering a selection of relevant physics- and statistics-based scientific models as well as aselection of related prediction models, in order to provide an updated operational scenario for space weather applications. The characteristics and outcomes of the considered scientific and prediction models indicate that they only partially cope with the complex nature of solar activity for the lack of a detailed knowledge of the underlying physics. This is indicated by the fact that, on one hand, scientific models based on chaos theory and non-linear dynamics reproduce better the observed features, and, on the other hand, that prediction models based on statistics and artificial neural networks perform better. To date, the solar weather prediction success at most time and spatial scales is far from being satisfactory, but the forthcoming ground- and space-based high-resolution observations can add fundamental tiles to the modelling and predicting frameworks as well as the application of advanced mathematical approaches in the analysis of diachronic solar observations, that are a must to provide comprehensive and homogeneous data sets.peerReviewe