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

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Heterocyclic amine directed synthesis of metal(II)-oxalates: investigating the magnetic properties of two complete series of chains with S = 5/2 to S = 1/2

We report here two series of coordination polymer chains: the first being [M(II)(ox)(bnz)2]n (M = Mn 1, Fe 2, Co 3, Ni 4, Cu 5 and Zn 6; ox = oxalate C2O42-; bnz = benzimidazole) and the second [M(II)(ox)(btz)2]n (M = Mn 7, Fe 8, Co 9, Ni 10, Cu 11 and Zn 12; btz = benzotriazole). The first series displays an unusual homometallic [–Mi–Mii–Mii–]n chain topology and the second series is isostructural to [Fe(II)(ox)(btz)2]n, originally reported by Jia et al. (Collect. Czech. Chem. Commun., 2002, 67, 1609–1615). These two series allow us to make comparisons between the spin state of each metal and the magnetic coupling interaction within an isostructural series spanning the full range of spin states available in 3d metals and to investigate which models are the best to use in each case. Compound 8 is a single-chain magnet, the behaviour through spin-canting arising from a Dzyaloshinskii-Moriya interaction. Additionally, we have synthesised a two-dimensional coordination polymer {[Zn(II)(bnz)4][Zn(II)2(ox)3]}n ( 13), in which distorted hexagonal [Zn(II)2(ox)3]n2n- layers are hydrogen bonded by [Zn(II)(bnz)4]2+ cations to give an interlayer separation of 12.001(2) Å

Knowledge gaps in the biology, ecology, and management of the Pacific crown-of-thorns sea star, Acanthaster sp., on Australia's Great Barrier Reef

Published online 17 November 2021Crown-of-thorns sea stars (Acanthaster sp.) are among the most studied coral reef organisms, owing to their propensity to undergo major population irruptions, which contribute to significant coral loss and reef degradation throughout the Indo-Pacific. However, there are still important knowledge gaps pertaining to the biology, ecology, and management of Acanthaster sp. Renewed efforts to advance understanding and management of Pacific crown-of-thorns sea stars (Acanthaster sp.) on Australia’s Great Barrier Reef require explicit consideration of relevant and tractable knowledge gaps. Drawing on established horizon scanning methodologies, this study identified contemporary knowledge gaps by asking active and/or established crown-of-thorns sea star researchers to pose critical research questions that they believe should be addressed to improve the understanding and management of crown-of-thorns sea stars on the Great Barrier Reef. A total of 38 participants proposed 246 independent research questions, organized into 7 themes: feeding ecology, demography, distribution and abundance, predation, settlement, management, and environmental change. Questions were further assigned to 48 specific topics nested within the 7 themes. During this process, redundant questions were removed, which reduced the total number of distinct research questions to 172. Research questions posed were mostly related to themes of demography (46 questions) and management (48 questions). The dominant topics, meanwhile, were the incidence of population irruptions (16 questions), feeding ecology of larval sea stars (15 questions), effects of elevated water temperature on crown-of-thorns sea stars (13 questions), and predation on juveniles (12 questions). While the breadth of questions suggests that there is considerable research needed to improve understanding and management of crown-of-thorns sea stars on the Great Barrier Reef, the predominance of certain themes and topics suggests a major focus for new research while also providing a roadmap to guide future research efforts.Morgan S. Pratchett … Camille Mellin … et al

An empirical study of the role of the corporate HR function in global talent management in professional and financial service firms in the global financial crisis

This study presents an empirical exploration of a theory-driven framework of corporate human resource (CHR) roles in global talent management (GTM). Specifically, it expands our knowledge of the process of GTM in two sectors: financial and professional services. Based on in-depth interview data from two firms, the study finds evidence of four distinct roles for CHR in facilitating successful GTM. The different business contexts are however critical to understanding the findings; in particular, the study demonstrates how CHR roles in GTM are affected by the approach to international business strategy and GTM, extent of corporate centralisation, and the business context, particularly the impact of the 2008 global financial services crisis. The study also shows the importance of a micro-component approach to the study of the GI-LR balance in GTM. GTM strategy is also found to be highly embedded in the broader business structure and shifts in the direction of globalisation within the sector, entailing epochs and episodes of internationalisation. Future GTM research needs to be more closely embedded in the strategic pathways of the firm