Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Activation of inflammatory responses in human U937 macrophages by particulate matter collected from dairy farms: an in vitro expression analysis of pro-inflammatory markers

Abstract Background The purpose of the present study was to investigate activation of inflammatory markers in human macrophages derived from the U937 cell line after exposure to particulate matter (PM) collected on dairy farms in California and to identify the most potent components of the PM. Methods PM from different dairies were collected and tested to induce an inflammatory response determined by the expression of various pro-inflammatory genes, such as Interleukin (IL)-8, in U937 derived macrophages. Gel shift and luciferase reporter assays were performed to examine the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like-receptor 4 (TLR4). Results Macrophage exposure to PM derived from dairy farms significantly activated expression of pro-inflammatory genes, including IL-8, cyclooxygenase 2 and Tumor necrosis factor-alpha, which are hallmarks of inflammation. Acute phase proteins, such as serum amyloid A and IL-6, were also significantly upregulated in macrophages treated with PM from dairies. Coarse PM fractions demonstrated more pro-inflammatory activity on an equal-dose basis than fine PM. Urban PM collected from the same region as the dairy farms was associated with a lower concentration of endotoxin and produced significantly less IL-8 expression compared to PM collected on the dairy farms. Conclusion The present study provides evidence that the endotoxin components of the particles collected on dairies play a major role in mediating an inflammatory response through activation of TLR4 and NF-κB signaling

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Evaluation of road sweepers' ability to reduce PM10 concentration

I föreliggande projekt har tre städmaskiners effekt på PM10-halterna i luften och på vägytan provats. Två delstudier har genomförts: en i gatumiljö på Sveavägen i Stockholm och en med kontrollerade försök på Barkarby flygplats. Försöken på Sveavägen visade att maskinernas effekt på de totala PM10-halterna var liten. Under särskilt gynnsamma meteorologiska förhållanden kunde dock signifikanta minskningar av det lokala bidraget på upp till 20 % konstateras. Maskin A bidrog oftare till förhöjda partikelhalter vid själva passagen än maskin B, medan maskin B oftare bidrog till förhöjda NOx-halter. Dammförrådet på vägytan visade sig svårt att utvärdera. Längs maskin A:s sträcka fanns dock det huvudsakliga förrådet av damm längs vägkanten, medan förrådet var störst längs vägmitten på maskin B:s sträcka. Försöken på Barkarby visade att maskin B, under torra förhållanden (maskin A utgick) förmådde städa upp ett utlagt material till ca 85\u9695 % (något lägre för PM10). Vid fuktiga förhållanden (maskin B utgick) var effektiviteten för maskin A drygt 40 % för hela materialet, medan effektiviteten för PM10 var avsevärt lägre (ca 5 %). Maskin C, som endast deltog i det fuktiga försöket, städade upp ca 99 % av det utlagda materialet och effektiviteten för PM10 var densamma. Sammantaget visar detta projekt att städmaskiner kan bidra till minskade halter av PM10 i miljöer där uppvirvling är en viktig partikelkälla, men även att städteknik och stödstrategi behöver utvecklas för att fungera bra under olika meteorologiska förhållanden.In this project three road sweepers' effect on PM10 concentrations in ambient air and on the road surface has been tested. Two studies have been carried out; one in street environment at Sveavägen in central Stockholm, Sweden, and one with controlled trials at Barkarby airport. The tests at Sveavägen showed that the sweepers' effect on total PM10 concentrations was small. In particularly favourable meteorological conditions, however, significant decreases in the local PM10 contribution of up to 20% could be found. Sweeper A contributed more often to elevated PM10 concentration during drive-by than sweeper B, while sweeper B more frequently contributed to elevated NOx levels. The dust depot on the road surface proved difficult to evaluate. In sweeper A's road stretch was, however, the main depot along the roadside, while it was greatest along the road center in sweeper B's stretch. Tests at Barkarby showed that sweeper B, under dry conditions (sweeper A was deleted) managed to clean up an applied material to about 85-95% (slightly lower for PM10). In moist conditions (sweeper B was deleted) the efficiency of sweeper A was slightly over 40% for the entire material, while significantly lower (approx. 5%) for PM10. Sweeper C, which only took part in the moist test, cleaned approximately 99% of the applied material and the efficiency for PM10 was the same. Overall, this project shows that road sweepers can contribute to decreased concentrations of PM10 in environments where road dust suspension is an important source of particulate matter, but also that sweeping technology and sweeping strategy need to be developed to work well under different meteorological conditions

Reconfigurable robotic platforms for structural health monitoring

This paper looks at reconfigurable robotic platforms for structural health monitorin