Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Hematoma intraparenquimatoso cerebral espontâneo: aspectos à tomografia computadorizada Spontaneous cerebral intraparenchymatous hematoma: computed tomography findings

OBJETIVO: Identificar os aspectos mais freqüentes do hematoma intraparenquimatoso cerebral espontâneo observados na tomografia computadorizada. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os exames de tomografia computadorizada de 250 pacientes com hematoma intraparenquimatoso cerebral espontâneo, provenientes de três diferentes hospitais da cidade do Rio de Janeiro. RESULTADOS: O hematoma intraparenquimatoso cerebral profundo foi o de maior incidência, equivalendo a 54,4% (136 casos), seguido do lobar com 34,8% (87 casos). Mais raramente, observou-se sangramento cerebelar em 8,4% (21 casos) e do tronco cerebral em 2,4% (seis casos) dos pacientes. CONCLUSÃO: A cefaléia foi o sintoma mais comum e a hipertensão arterial foi o sinal mais freqüentemente apresentado. A drenagem do hematoma para o sistema ventricular ocorreu mais comumente nos hematoma profundos.<br>OBJECTIVE: To identify the most frequent aspects of spontaneous cerebral intraparenchymatous hematoma found at computed tomography examinations. MATERIALS AND METHODS: We reviewed, retrospectively, the computed tomography studies of 250 patients with spontaneous intracerebral hemorrhage carried out in three hospitals in Rio de Janeiro, Brazil. RESULTS: Deep intracerebral hematomas showed the highest incidence and were observed in 54.4% of the cases (136 patients) followed by lobar hemorrhage in 34.8% of the cases (87 patients). Cerebelar hemorrhage and brainstem bleeding were more rarely observed, occurring in 8.4% (21 patients) and 2.4% (six patients) of the cases, respectively. CONCLUSION: Chronic headache was the most frequent symptom whereas hypertension was observed in the majority of the cases. Blood draining into the ventricular system occurred more frequently in patients with deep hematomas

Factors influencing farmers’ behavior in rice seed selling in the market: a case study in the Tarai region of Nepald

The importance of rice in food security and livelihoods of Nepalese people is well recognized but the seed supply system of this crop in the rural areas is poorly developed. To increase farmers' access to a wide range of rice varietal choices in a cost effective way, some farmers, organized in groups or cooperatives, have started producing and marketing rice seed through development projects in recent years. But very limited information has been published about the performance of the farmers in rice seed marketing. In this study, we analyze the impact of households' socio-economic variables on market participation and volume of rice seed sold, using a Heckman selection model. Data for the study were collected from three Tarai districts (Siraha, Kailali and Chitwan) in Nepal with a sample size of 180, that is, 60 households from each district. Result shows that 65% of households sell 64% of rice seed produced. Households with agricultural training, share contribution to their organization and higher livestock numbers are more likely to participate in the market. Similarly, households with older household heads, higher operational land, and access to an irrigation facility sell a higher amount of rice seed in the market. Seed price has a positive influence both on market participation and seed volume sold

HCI and Usability Principles and Guidelines in the Website Development Process: An International Perspective

This chapter provides an answer to the question “Do industry practitioners consider that human computer interaction (HCI) and usability principles and guidelines are essential in the website development process?” The answer was sought by means of an online survey (N = 126), of Information Systems(IS)/Information Technology (IT) personnel in Australia and Portugal, that allowed the collection of both quantitative and qualitative data. Explanatory analysis was conducted using descriptive statistics, including frequencies and an independent sample T-test. The study findings suggest that both HCI and Usability were significant aspects of the website development process especially in the marketing websites, as their inclusion will encourage users to revisit these websites and thereby increase businesses’ profits. Usability and HCI features are especially important in the design stage to improve the structure and functionality of a website. The conclusions drawn in this chapter will assist IS/IT industry practitioners in Australia and Portugal to implement HCI and usability approaches by means of a New Participative Methodology for Marketing Websites (NPMMW)