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Search: WFRF:(Varghese V)

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1.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
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  • Niemi, MEK, et al. (author)
  • 2021
  • swepub:Mat__t
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  • Kaptoge, S., et al. (author)
  • World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
  • 2019
  • In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
  • Journal article (peer-reviewed)abstract
    • Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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  • Nagaraja, Ch., et al. (author)
  • Opening remarks
  • 2016
  • Conference paper (peer-reviewed)
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  • Algenaid, Wael, 1992-, et al. (author)
  • Influence of microstructure on the erosion behaviour of suspension plasma sprayed thermal barrier coatings
  • 2019
  • In: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 375, s. 86-99
  • Journal article (peer-reviewed)abstract
    • Thermal barrier coatings (TBCs) are applied on the surface of hot parts of gas turbine engines to increase the turbine efficiency by providing thermal insulation and to protect the engine parts from the harsh environment. Typical degradation of TBCs can be attributed to bond coat oxidation, thermal stress etc. In addition to this, erosion can also lead to partial or complete removal of the TBCs especially when the engine operates under erosive environment such as flying over desert area, near active volcanic or offshore ocean environment. Suspension Plasma Spraying (SPS) is a promising technique for TBC applications by virtue of its ability to produce a strain-tolerant porous-columnar microstructure that combines the benefits of both electron beam physical vapor deposited (EB-PVD) as well as atmospheric plasma sprayed (APS) coatings. This work investigates the influence of various coating microstructures produced by SPS on their erosion behavior. Six different coatings with varied microstructures produced using different suspensions with distinct characteristics were studied and their erosion resistance was compared. Results showed significant influence of SPS TBCs microstructures on the erosion resistance. Furthermore, the erosion resistance of SPS TBCs showed a close correlation between fracture toughness and the erosion rate, higher fracture toughness favours superior erosion resistance. © 2019 Elsevier B.V.
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  • Eratne, D., et al. (author)
  • Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings
  • 2022
  • In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:11, s. 2218-2233
  • Journal article (peer-reviewed)abstract
    • Introduction Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders. Methods Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND). Results A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND. Discussion We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
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  • Goel, Sneha, et al. (author)
  • Role of HIPing and Heat Treatment on Properties of Alloy 718 Fabricated by Electron Beam Melting
  • 2019
  • In: Euro PM 2019 Congress and Exhibition.
  • Conference paper (peer-reviewed)abstract
    • Although additive manufacturing (AM) of difficult-to-machine materials can open new design possibilities for production of parts with complex geometries, AM builds are characterized by presence of detrimental defects like shrinkage/ gas porosity and lack-of-fusion. Microstructural inhomogeneity, anisotropy in properties and formation of undesirable phases are added concerns. Motivated by the need for investigation of appropriate thermal post-treatments to eliminate defects, and to achieve desired microstructural and mechanical properties, the influence of hot isostatic pressing (HIPing) and heat treatment on electron beam melted (EBM) Alloy 718 specimens built at different heights from the base-plate has been studied. While HIPing led to orders of magnitude reduction in defect content, conventional heat treatment without applied pressure was found to have no effect. Thermal post-treatment was found to eliminate inherent variability in phase constitution and hardness of as-built specimens. HIPing at high temperature was accompanied by grain coarsening, suggesting modification of the HIPing protocol.
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  • Pennells, Lisa, et al. (author)
  • Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
  • 2019
  • In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
  • Journal article (peer-reviewed)abstract
    • Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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  • Babrzadeh, F., et al. (author)
  • Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance
  • 2013
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 68:2, s. 414-418
  • Journal article (peer-reviewed)abstract
    • Objectives: To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs. Methods: We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing. Results: For each of the nine virus samples, deep sequencing showed that each of the individual viruses within a sample contained nearly all of the mutations detected by Sanger sequencing. Indeed, a median of 94.9% of deep sequence reads had each of the PI resistance mutations present as a single chromatographic peak in the Sanger sequence. A median of 5.0% of reads had all but one of the Sanger mutations that were not part of an electrophoretic mixture. Conclusions: The collinearity of PI resistance mutations in the nine virus samples demonstrated that pan-PI-resistant viruses are able to replicate in vivo despite their highly mutated protease enzymes. We hypothesize that the marked collinearity of PI resistance mutations in pan-PI-resistant virus populations results from the unique requirements for multi-PI resistance and the extensive cross-resistance conferred by many of the accessory PI resistance mutations.
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  • D'Souza, K., et al. (author)
  • Autotaxin-Lysophosphatidic Acid Signaling Contributed to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism
  • 2018
  • In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 59:10, s. 1805-1817
  • Journal article (peer-reviewed)abstract
    • Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX +/-) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. HFHS-fed ATX +/- mice also had improved insulin-stimulated AKT phosphorylation in white adipose tissue, liver, heart, and skeletal muscle. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function.
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  • Laskar, Partha, et al. (author)
  • Advances in Intracellular and On-Surface Polymerization in Living Cells : Implications for Nanobiomedicines
  • 2023
  • In: Advanced NanoBiomed Research. - : Wiley-VCH Verlagsgesellschaft. - 2699-9307. ; 3:8
  • Research review (peer-reviewed)abstract
    • The cellular environment offers some unique features to carry out polymerizations under controlled conditions. Polymerization of monomers in cellular compartments and on the surface of living organisms holds much promise in the engineering of biofunctional synthetic polymers for sensing and probing cell behavior and of late has received significant interest. This effort lies at the interface of synthetic biology and polymer chemistry and can pave the way for innovative solutions to many existing challenges in healthcare, environment, energy, and the study of the "origin of life". Herein, recent advances in controlled polymerization strategies for intracellular and surface of living cells are presented with a particular emphasis on nanobiomedicines. Furthermore, polymerization strategies, cytocompatible monomer structures, compatible cell lines and microorganisms, nature of stimulus, catalysts, along with specific polymerization conditions to produce non-natural biofunctional polymers that can undergo polymerization-induced self-assembly within and onto the living cells are presented in detail. Furthermore, the review offers a window into the future of such novel emerging synthetic bionano systems in biomedical sciences.
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  • Mock, Thomas, et al. (author)
  • Multiomics in the central Arctic Ocean for benchmarking biodiversity change
  • 2022
  • In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 20:10
  • Journal article (peer-reviewed)abstract
    • Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.
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  • Rahman, Cheryl V., et al. (author)
  • PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties
  • 2013
  • In: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 101B:4, s. 648-655
  • Journal article (peer-reviewed)abstract
    • Biodegradable polymer scaffolds have great potential for regenerative medicine applications such as the repair of musculoskeletal tissues. Here, we describe the development of scaffolds that blend hydrogel components with thermoplastic materials, combining the unique properties of both components to create mouldable formulations. This study focuses on the structural and mechanical properties of the composite scaffolds, produced by combining temperature-sensitive poly(DL-lactic acid-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) particles with a hydrogel component [Pluronic F127, fibrin or hyaluronic acid (HyA)]. The composite formulations solidified over time at 37 degrees C, with a significant increase (p 0.05) in compressive strength observed from 15 min to 2 h at this temperature. The maximum compressive strength was 1.2 MPa for PLGA/PEG-Pluronic F127 scaffolds, 2.4 MPa for PLGA/PEG-HyA scaffolds and 0.6 MPa for PLGA/PEG-fibrin scaffolds. Porosity for each of the PLGA/PEG-hydrogel formulations tested was between 50 and 51%. This study illustrates the ability to combine this thermoplastic PLGA/PEG system with hydrogels to fabricate composite scaffolds, and demonstrates that altering the particle to hydrogel ratio produces scaffolds with varying mechanical properties.
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  • Varghese, Mercy, et al. (author)
  • Characteristics of CCN activation and cloud microphysics over the east coast of India during the Northeast Monsoon onset
  • 2021
  • In: Atmospheric Research. - : Elsevier BV. - 0169-8095. ; 257
  • Journal article (peer-reviewed)abstract
    • Airborne observations conducted during the Northeast Monsoon onset as part of the Cloud Aerosol Interaction and Precipitation Enhancement Experiment (CAIPEEX 2011) are used to link the activation properties of aerosols with the observed cloud microphysics. This study illustrates the significant spatial variability in the aerosol spectrum, cloud condensation nuclei (CCN) activation characteristics, and the cloud droplet spectral properties over a coastal and an inland location. High concentrations of Aitken mode and black carbon aerosols were observed in the free troposphere and are attributed to the convectively transported smoke and aerosols from the coastal boundary layer. The assumption of an internally mixed organic and inorganic aerosol composition provided a better CCN closure over assumptions of either purely organic or purely inorganic aerosols. The coastal clouds were equally polluted as the inland clouds with high cloud droplet number concentrations near the cloud base. The vertical distribution of cloud droplet spectral characteristics was similar in both coastal and inland clouds. An increase in droplet number concentration up to 2 km above the cloud base indicated a prominent influence of submicron particles on the cloud microphysical parameters. Evidence for an enhanced concentration of supercooled drops above the freezing level up to temperatures below −12 °C is documented. The secondary ice production was evident through observations of graupel and snow particles. Heavy loading of aerosols near the cloud base leads to enhanced mixed-phase processes in these clouds.
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