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| 2. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- 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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| 7. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 8. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 11. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 12. |
- Dutta, Tanmoy, 1998, et al.
(författare)
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Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED)
- 2023
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Failure of rapid re-epithelialization within 10-14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell-cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNF alpha, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell-cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNF alpha, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea.
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| 15. |
- Ray, A. K., et al.
(författare)
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Damage resistance of a thermal barrier coated superalloy used in aero turbine blade under accelerated creep condition
- 2009
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Ingår i: High Temperature Materials and Processes. - 0334-6455 .- 2191-0324. ; 28:1-2, s. 35-53
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Tidskriftsartikel (refereegranskat)abstract
- This paper highlights the hot tensile and accelerated creep properties of a thermal barrier coated (TBC) AE 437A alloy used as a candidate blade material in aero engines. Acoustic emission technique has been utilised to characterise the ductile-brittle transition temperature of the bond coat. Results revealed that the DBTT (ductile to brittle transition temperature) of this bond coat is around 923 K, which is in close proximity to the value reported for NiCoCrAlY type of bond coat. Finite element technique used for analysing the equivalent stresses in the bond coat well within the elastic limit, revealed highest order of equivalent stress at 1073 K as the bond coat is ductile above 923 K. The lifetime of the TBC coated superai loy was superior to that of the bare substrate and that oxidation is likely the cause of the reduced life of the bare substrate as compared to the coated substrate while stress rupture or accelerated creep experiments are carried out in an oxidizing environment.. Delamination of the bond coat and that of the TBC at high stresses during accelerated creep was evident. During accelerated creep, the mode of fracture in the substrate at very high stresses was transgranular whereas that at low stresses was intergranular.
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| 16. |
- Bisht, D. S., et al.
(författare)
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Tethered balloon-born and ground-based measurements. of black carbon and particulate profiles within the lower troposphere during the foggy period in Delhi, India
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 573, s. 894-905
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Tidskriftsartikel (refereegranskat)abstract
- The ground and vertical profiles of particulate matter (PM) were mapped as part of a pilot study using a Tethered balloon within the lower troposphere (1000 m) during the foggy episodes in the winter season of 2015-16 in New Delhi, India. Measurements of black carbon (BC) aerosol and PM <2.5 and 10 mu m (PM2.5 &PM-10 respectively) concentrations and their associated particulate optical properties along with meteorological parameters were made. The mean concentrations of PM2.5, PM10, BC370 (nm), and BC880 nm were observed to be 146.8 +/- 42.1, 245.4 +/- 65.4, 30.3 +/- 122, and 24.1 +/- 103 mu g m(-3), respectively. The mean value of PM2.5 was similar to 12 times higher than the annual US-EPA air quality standard. The fraction of BC in PM2.5 that contributed to absorption in the shorter visible wavelengths (BC370 nm) was-21%. Compared to clear days, the ground level mass concentrations of PM2.5 and BC370 nm particles were substantially increased (59% and 24%, respectively) during the foggy episode. The aerosol light extinction coefficient (sigma(ext)) value was much higher (mean: 610 Mm(-1)) during the lower visibility (foggy) condition. Higher concentrations of PM2.5 (89 mu g m(-3)) and longer visible wavelength absorbing BC880 am (25.7 mu g m(-3)) particles were observed up to 200 m. The BC880 nm and PM2.5 aerosol concentrations near boundary layer (1 km) were significantly higher (similar to 1.9 and 12 mu g m(-3)), respectively. The BC (i.e BCtot) aerosol direct radiative forcing (DRF) values were estimated at the top of the atmosphere (TOA), surface (SFC), and atmosphere (ATM) and its resultant forcing were- 75.5 Wm(-2) at SFC indicating the cooling effect at the surface. A positive value (20.9 Wm(-2)) of BC aerosol DRF at TOA indicated the warming effect at the top of the atmosphere over the study region. The net DRF value due to BC aerosol was positive (96.4 Wm(-2)) indicating a net warming effect in the atmosphere. The contribution of fossil and biomass fuels to the observed BC aerosol DRF values was -78% and-22%, respectively. The higher mean atmospheric heating rate (2.71 K clay(-1)) by BC aerosol in the winter season would probably strengthen the temperature inversion leading to poor dispersion and affecting the formation of clouds. Serious detrimental impacts on regional climate due to the high concentrations of BC and PM (especially PM2.5) aerosol are likely based on this study and suggest the need for immediate, stringent measures to improve the regional air quality in the northern India.
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| 17. |
- Cole, J. W., et al.
(författare)
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The copy number variation and stroke (CaNVAS) risk and outcome study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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| 20. |
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| 21. |
- Imani, Roghayeh, et al.
(författare)
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Band edge engineering of TiO2@DNA nanohybrids and implications for capacitive energy storage devices.
- 2015
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Ingår i: Nanoscale. - : RSC Publishing. - 2040-3364 .- 2040-3372. ; 7:23, s. 10438-10448
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Tidskriftsartikel (refereegranskat)abstract
- Novel mesoporous TiO2@DNA nanohybrid electrodes, combining covalently encoded DNA with mesoporous TiO2 microbeads using dopamine as linker, were prepared and characterised for application in supercapacitors. Detailed information about donor density, charge transfer resistance and chemical capacitance, which have important role in the performance of an electrochemical device, were studied by electrochemical methods. The results indicated the improvement of electrochemical performance of TiO2 nanohybrid electrode by DNA surface functionalisation. A supercapacitor was constructed from TiO2@DNA nanohybrids with PBS as electrolyte. From the supercapacitor experiment, it was found that the addition of DNA played an important role in improving the specific capacitance (Cs) of the TiO2 supercapacitor. The highest Cs value of 8 F/g was observed for TiO2@DNA nanohybrids. The nanohybrid electrodes were shown to be stable over long-term cycling, retaining 95% of their initial specific capacitance after 1500 cycles.
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| 22. |
- Imani, Roghayeh, et al.
(författare)
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Band edge engineering of TiO2@DNA nanohybrids and implications for capacitive energy storage devices
- 2015
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:23, s. 10438-10448
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Tidskriftsartikel (refereegranskat)abstract
- Novel mesoporous TiO2@DNA nanohybrid electrodes, combining covalently encoded DNA with mesoporous TiO2 microbeads using dopamine as a linker, were prepared and characterised for application in supercapacitors. Detailed information about donor density, charge transfer resistance and chemical capacitance, which have an important role in the performance of an electrochemical device, were studied by electrochemical methods. The results indicated the improvement of electrochemical performance of the TiO2 nanohybrid electrode by DNA surface functionalisation. A supercapacitor was constructed from TiO2@DNA nanohybrids with PBS as the electrolyte. From the supercapacitor experiment, it was found that the addition of DNA played an important role in improving the specific capacitance (C-s) of the TiO2 supercapacitor. The highest Cs value of 8 F g(-1) was observed for TiO2@DNA nanohybrids. The nanohybrid electrodes were shown to be stable over long-term cycling, retaining 95% of their initial specific capacitance after 1500 cycles.
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| 23. |
- Kandpal, M, et al.
(författare)
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Dysbiosis of Gut Microbiota from the Perspective of the Gut-Brain Axis: Role in the Provocation of Neurological Disorders
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.
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| 25. |
- Kukkonen, J., et al.
(författare)
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Towards a Comprehensive Evaluation of the Environmental and Health Impacts of Shipping Emissions
- 2022
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Ingår i: Springer Proceedings in Complexity. - Cham : Springer International Publishing. - 2213-8684 .- 2213-8692. ; , s. 329-336
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Konferensbidrag (refereegranskat)abstract
- We present a new concept for marine research, applied in the EU-funded project EMERGE, “Evaluation, control and Mitigation of the EnviRonmental impacts of shippinG Emissions” (2020–2024; https://emerge-h2020.eu/ ). For the first time, both the various marine and atmospheric impacts of the shipping sector have been and will be comprehensively analyzed, using a concerted modelling and measurements framework. The experimental part of the project focuses on five European geographical case studies in different ecologically vulnerable regions, and a mobile onboard case study. The EMERGE consortium has also developed a harmonised and integrated modelling framework to assess the combined impacts of shipping emissions, both (i) on the marine ecosystems and (ii) the atmospheric environment. The first results include substantial refinements of a range of models to be applied, especially those for the STEAM and OpenDrift models. In particular, the STEAM (Ship Traffic Emission Assessment Model) model has been extended to allow for the effects of atmospheric and oceanographic factors on the fuel consumption and emissions of the ships. The OpenDrift model has been improved to take into account the partitioning, degradation, and volatilization of pollutants in water. The predicted emission and discharge values have been used as input for both regional scale atmospheric dispersion models, such as WRF-CMAQ (Weather Research and Forecasting—Community Multiscale Air Quality Model) and SILAM (System for Integrated modeLling of Atmospheric composition), and water quality and circulation models, such as OpenDrift (Open source model for the drifting of substances in the ocean) and Delft3D (oceanographic model). The case study regions are Eastern Mediterranean, Northern Adriatic Sea, the Lagoon of Aveiro, the Solent Strait and the Öresund Strait. We have also conducted a substantial part of the experimental campaigns scheduled in the project. The final assessment will include the benefits and costs of control and mitigation options affecting water quality, air pollution exposure, health impacts, climate forcing, and ecotoxicological effects and bioaccumulation of pollutants in marine biota.
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