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

Improving Planning Support : The use of planning support systems for spatial planning

Spatial planning is one of the most complex activities of public organizations. Since approximately halfway the 1990s a new generation of geo-information technologies has become available to support those involved in planning in handling the complexity: Planning Support Systems (PSS). PSS consist of a combination of planning related theory, data, information, knowledge, methods and instruments, that take the form of an integrated environment with a shared interface. Many see PSS as promising support tools to handle complexity of planning, however usage in planning practice stays far behind of supply, which is problematic regarding this assumed potential. This project aims to explain the relative under-use of PSS in planning practice and formulate guidelines for enhanced PSS application in spatial planning. For this purpose the study combines insights of PSS users, PSS experts and PSS system developers. The problem has been studied from three approaches that each emphasize specific aspects of usage of PSS. Results of an analysis of instrumental quality of the existing PSS show that PSS technology is still in an early stage of development. The analysis also shows that there exists a dichotomy between the demands of planning practice and the supply of PSS: practice demands in particular simple systems, while many developers provide advanced systems. Results of an analysis of acceptance of PSS show that the main causes for the limited acceptance of PSS are: the lack of awareness of the existence and potential of PSS, the lack of experience with PSS, and the lack of intention to start using PSS among the intended users. Results of an analysis of diffusion of PSS show that diffusion is most likely to take place bottom-up. Geo-information specialists are the most suitable employees in practice to take the PSS from the extra organizational environment. However, bottom-up diffusion is often blocked by managers who perceive investments in ICT such as PSS as a risk. The instrument, user and transfer approach were subsequently applied to explain differences in usage of PSS types. Results show that PSS with the primary aim of informing the actors involved in planning are applied widely, while PSS with the primary aim of supporting communication and analysis are much less widely used. The primary causes of less wide usage of PSS for communication and analysis are lack of experience with these PSS, lack of awareness of their existence and potential, and lack of instrumental quality of many of these PSS. Secondary causes are hampered acceptance and diffusion. To enhance usage of PSS in planning practice, we recommend to the actors involved in PSS development and application of PSS start improving their communication and cooperation in development and application of PSS. Interactive learning processes in which PSS developers, researchers and practitioners are involved can constitute the right combination of knowledge and experience to come to successful applications. These can furthermore lead to the availability of examples that may convince others of the use of applying PSS. This can stimulate awareness, experience, instrumental quality, acceptance and diffusion of PSS

Bottlenecks blocking widespread usage of planning support systems

Research on planning support systems (PSS) is characterized by a strong emphasis on the supply side, whereas little research has been undertaken on the successes and failures in the adoption of PSS within the planning community (demand side). What becomes clear from the existing research is that usage is not widespread. In this paper we aim to find the main bottlenecks blocking the widespread use of PSS in spatial planning. To achieve this, a global online survey was conducted in which almost 100 PSS experts participated and for which a theoretical framework from the field of business studies served as a basis. The results show that a multitude of factors cause the underutilization of PSS, their characteristics being human, organizational and institutional, as well as technical. In particular, the lack of awareness of and experience with PSS, alongside the relative lack of recognition of the value of PSS within the spatial planning community, tend to block widespread usage and adoption of PSS in planning practice. On this basis, we offer recommendations for the enhancement of PSS adoption, namely to disseminate more profoundly information and knowledge about the existence and benefits of PSS within the spatial planning community. Real-world example projects and in-depth research on potential benefits of PSS application in planning practice will be crucial in this.

A SWOT analysis of planning support systems

Insight into the strengths, weaknesses, opportunities, and threats (SWOT) of planning support systems (PSS) is fragmented between users and system developers. The lack of combined insights blocks development in the right direction and makes potential users hesitant to apply PSS in planning. This study presents SWOT of PSS from a combined user – developer perspective. We first express them in terms of combinations of planning task, PSS information function, and user, and subsequently use a literature survey, a series of interviews, and a web survey to gather views from developers, users, and PSS experts. The analysis shows that planners mainly use simple information storage and retrieval systems for exploration tasks, while the majority of PSS are technically much more advanced and aim to support complex tasks. The potential of these advanced PSS can only be realized if planners and system developers start to share knowledge and demands and identify opportunities in a cooperative PSS-development process. Without such a process, the advantages and opportunities of PSS will remain unexploited.

A 12-wk whole-grain wheat intervention protects against hepatic fat : the Graandioos study, a randomized trial in overweight subjects

Background: Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions. Objective: The aim of this study was to investigate the potential benefits of WGW consumption compared with RW consumption on liver health and associated parameters. Design: We performed a double-blind, parallel trial in which 50 overweight 45- to 70-y-old men and postmenopausal women were randomly allocated to a 12-wk intervention with either WGW (98 g/d) or RW (98 g/d) products. Before and after the intervention we assessed intrahepatic triglycerides (IHTGs) and fat distribution by proton magnetic resonance spectroscopy/magnetic resonance imaging, fecal microbiota composition, adipose tissue gene expression, and several fasting plasma parameters, as well as postprandial plasma lipids after a mixed meal. Results: Fasting plasma cholesterol, triglycerides, nonesterified fatty acids, and insulin were not affected by RW or WGW intervention. We observed a substantial increase of 49.1% in IHTGs in the RW when compared with the WGW group (P = 0.033). Baseline microbiota composition could not predict the increase in IHTGs after RW, but gut microbiota diversity decreased in the RW group when compared with the WGW group (P = 0.010). In the WGW group, we observed increased postprandial triglyceride levels compared with the RW group (P = 0.020). In addition, the WGW intervention resulted in a trend towards lower fasting levels of the liver acute-phase proteins serum amyloid A (P = 0.057) and C-reactive protein (P = 0.064) when compared to the RW intervention. Conclusions: A 12-wk RW intervention increases liver fat and might contribute to the development of nonalcoholic fatty liver disease, whereas a 12-wk 98-g/d WGW intervention prevents a substantial increase in liver fat. Our results show that incorporating feasible doses of WGW in the diet at the expense of RW maintains liver health. The study was registered at clinicaltrials.gov as NCT02385149.</p

Knowledge deficit and fear of COVID-19 among higher education students during the first wave of the pandemic and implications for public health: a multi-country cross-sectional survey

Background Public health measures such as physical distancing and distance learning have been implemented during the COVID-19 pandemic. COVID-19 related knowledge deficit can increase fear that leads to negative mental health and COVID-19, especially among adolescents. Therefore, our study aimed to assess COVID-19 related knowledge deficit and its association with fear among higher education (HE) students during the first wave of COVID-19. Methods A cross-sectional survey, COVID-19 International Students Well-being Study (C-19 ISWS) was conducted in 133 Higher Education Institutions (HEIs) in 26 countries between April 27 and July 7, 2020. A stratified convenience sampling technique was used. Descriptive, bivariate, mixed-effect logistic regression analyses were conducted using R software. Results Out of 127,362 respondents, 72.1% were female, and 76.5% did not report a previous history of confirmed COVID-19. The majority of those without the previous infection 81,645 (83.7%) were from 21 European countries while the rest 15,850 (16.3%) were from 5 non-European countries. The most frequent correct response to COVID-19 related knowledge questions among respondents was having the virus without having symptoms (94.3%). Compared to participants with good knowledge, the odds of being afraid of acquiring SARS-COV-2 infection among those with poor knowledge was 1.05 (95%CI:1.03,1.08) and the odds of being afraid of contracting severe COVID-19 was 1.36 (95%CI:1.31,1.40). Conclusion COVID-19 related knowledge was independently associated with both fear of acquiring SARS-COV-2 infection as well as contracting severe COVID-19. Our findings will serve as a basis for public health response for both the current and similar future pandemics by highlighting the need for addressing the COVID-19 knowledge deficit to fight the infodemic and prevent negative mental health outcomes

Demonstration of bacterial cells and glycocalyx in biofilms on human tonsils.

OBJECTIVES: To demonstrate mucosal biofilms in human tissue by direct visualization of bacteria and glycocalyx using confocal laser scanning microscopy with double fluorescent staining on tonsils and to compare the findings with the results of scanning electron microscopy analysis. DESIGN: Prospective study. SETTING: Tertiary university-based referral center. PATIENTS: Twenty-four tonsils were obtained from children with chronic or recurrent tonsillitis. INTERVENTIONS: Tonsils were prepared for analysis by scanning electronic microscopy and by confocal laser scanning microscopy. MAIN OUTCOME MEASURES: Double fluorescent staining for confocal laser scanning microscopy consisted of propidium iodide staining to detect bacterial cells and fluorescein isothiocyanate concanavalin A staining to detect the glycocalyx matrix. Images were analyzed for characteristic biofilm morphologic features by 3 investigators who evaluated the images independently in a blinded retrospective manner. Consensus of all observers was required to demonstrate the presence of a biofilm in a specimen. RESULTS: Findings from analyses using scanning electronic microscopy suggested the presence of biofilm formations on tonsils by showing bacterial cells in microcolonies. Double-staining technique using confocal laser scanning microscopy showed bacterial cells and the glycocalyx matrix, providing visual evidence for the presence of biofilms on tonsils. CONCLUSION: Using a novel visualization approach in single sections of human mucosal tissue, the presence of biofilms was demonstrated on tonsils in most (17/24 [70.8%]) patients with tonsillitis