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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). 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 analysis(3), 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 approach(4), 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 ancestry(5). 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.
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- Rehman, I. -U, et al.
(författare)
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Port site tuberculosis a rare post operation entity : A case report
- 2022
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Ingår i: Annals of Medicine and Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 2049-0801. ; 78
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Tidskriftsartikel (refereegranskat)abstract
- Laparoscopic cholecystectomy is one of the most common procedures done worldwide. Post-surgical site infections are common, yet there are occurrences of uncommon complications, including port site tuberculosis (TB). We report a case of a 62-year-old man who was the victim of post-surgical site infection of port sites caused probably by improper sterilization. The patient lacked any common symptoms of tuberculosis and his initial lab investigations were not affirmative. A biopsy depicting the growth of multiple epithelioid granulomas finally led to the diagnosis of port site tuberculosis. The patient was treated by incision and drainage followed by anti-tubercular therapy. This treatment regime showed complete resolution of disease on follow-ups. Such cases require multidisciplinary team (Surgery, Pathology and Infectious disease department in our case) inputs for prompt diagnosis and treatment.
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| 13. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 14. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 15. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 16. |
- Hussain, F., et al.
(författare)
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Electrochemical investigation of multi-fuel based low temperature nano-composite anode for solid oxide fuel cell
- 2019
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Ingår i: Journal of Power Sources. - : Elsevier B.V.. - 0378-7753 .- 1873-2755. ; 425, s. 147-152
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Tidskriftsartikel (refereegranskat)abstract
- Extensive efforts have been made in order to develop multi-fuel-based low temperature solid oxide fuel cell for direct conversion of hydrocarbons to electric power. It is extremely difficult to operate due to the C–H activation and its tremendously sluggish oxidation reduction in the low temperature range from 300 to 600 °C. The structural and electrochemical properties of novel anode material Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 have been investigated in the presence of hydrogen, natural gas, ethanol, glucose, and sugar-cane at low temperature of 600 °C. Through sol-gel method the proposed oxide material is synthesized. The composite average crystalline size has been found 25–90 nm by both scanning electron microscopy and X-ray diffraction techniques. The ultraviolet– visible and Fourier transform infrared techniques are used to determine band gap and absorption spectrum respectively. The power density of the cell at various fuels has been observed and measurements indicate that it varies from 57 to 315 mWcm −2 at 600 °C among different fuels at anode side. The current study reveals that proposed anode Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 is promising multi-fuel anode material for low-temperature solid oxide fuel cell, and it does not need to reform hydrocarbon fuels in order to fully utilize the advantage of these cells.
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| 18. |
- Kiani, Zia U. R., et al.
(författare)
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Measuring Awareness in Cross-Team Collaborations – Distance Matters
- 2013
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Konferensbidrag (refereegranskat)abstract
- Developing and maintaining team awareness within and across teams working in the same project helps team members in aligning their activities and facilitates implicit coordination. This requires both task and presence awareness. In this paper, we share our findings from a survey in which we measured the level of team awareness in cross-team collaborations with varying degree of separation. To measure the levels of awareness we asked questions like who is who, who knows what, who is on a vacation, who depends on whom and alike. Results from surveying 17 pairs of teams from 15 organizations indicate that level of awareness in cross-team collaborations is generally lower than that within the teams. We also found that task and presence awareness levels are independent and can vary. In addition to distance, we identified a few other factors with potential positive and negative influence on team awareness.
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| 19. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 20. |
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