SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Selvaraj S) "

Sökning: WFRF:(Selvaraj S)

  • Resultat 1-10 av 11
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Selvaraj, S., et al. (författare)
  • Prognostic Implications of Congestion on Physical Examination Among Contemporary Patients With Heart Failure and Reduced Ejection Fraction PARADIGM-HF
  • 2019
  • Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 140:17, s. 1369-1379
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background: The contemporary prognostic value of the physical examination— beyond traditional risk factors including natriuretic peptides, risk scores, and symptoms—in heart failure (HF) with reduced ejection fraction is unknown. We aimed to determine the association between physical signs of congestion at baseline and during study follow-up with quality of life and clinical outcomes and to assess the treatment effects of sacubitril/valsartan on congestion. Methods: We analyzed participants from PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) with an available physical examination at baseline. We examined the association of the number of signs of congestion (jugular venous distention, edema, rales, and third heart sound) with the primary outcome (cardiovascular death or HF hospitalization), its individual components, and all-cause mortality using time-updated, multivariable-adjusted Cox regression. We further evaluated whether sacubitril/valsartan reduced congestion during follow-up and whether improvement in congestion is related to changes in clinical outcomes and quality of life, assessed by Kansas City Cardiomyopathy Questionnaire overall summary scores. Results: Among 8380 participants, 0, 1, 2, and 3+ signs of congestion were present in 70%, 21%, 7%, and 2% of patients, respectively. Patients with baseline congestion were older, more often female, had higher MAGGIC risk scores (Meta-Analysis Global Group in Chronic Heart Failure) and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (P<0.05). After adjusting for baseline natriuretic peptides, time-updated Meta-Analysis Global Group in Chronic Heart Failure score, and time-updated New York Heart Association class, increasing time-updated congestion was associated with all outcomes (P<0.001). Sacubitril/valsartan reduced the risk of the primary outcome irrespective of clinical signs of congestion at baseline (P=0.16 for interaction), and treatment with the drug improved congestion to a greater extent than did enalapril (P=0.011). Each 1-sign reduction was independently associated with a 5.1 (95% CI, 4.7–5.5) point improvement in Kansas City Cardiomyopathy Questionnaire overall summary scores. Change in congestion strongly predicted outcomes even after adjusting for baseline congestion (P<0.001). Conclusions: In HF with reduced ejection fraction, the physical exam continues to provide significant independent prognostic value even beyond symptoms, natriuretic peptides, and Meta-Analysis Global Group in Chronic Heart Failure risk score. Sacubitril/valsartan improved congestion to a greater extent than did enalapril. Reducing congestion in the outpatient setting is independently associated with improved quality of life and reduced cardiovascular events, including mortality.
  •  
2.
  •  
3.
  •  
4.
  • Vivek, S.S., et al. (författare)
  • Impact and Durability Properties of Alccofine-Based Hybrid Fibre-Reinforced Self-Compacting Concrete
  • 2023
  • Ingår i: Case Studies in Construction Materials. - : Elsevier. - 2214-5095. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Many research works have already been made and are still in progress on metallic fibres, as their incorporation reduces the brittleness of the concrete and improves its resistance to the impact and crack propagation. But the use of such non-metallic fibres may induce corrosion which is a major problem to be addressed from the durability aspect. To overcome this problem, in the present research work, a non-metallic hybrid fibre combination was investigated with synthetic fibres like polypropylene and abaca fibres. Also, rather than using conventional cementitious materials such as silica fume, fly ash, and ground granulated blast furnace slag, a new generation of ultra-fine material namely alccofine was used as a partial replacement for the cement by 15%. Abaca fibre was utilised in a constant addition of 0.5% and blended with polypropylene fibre in a range varying from 0% to 2% with an increment of 0.5%. The fresh properties of self-compacting concrete (SCC) in mono and hybrid fibres combinations were assessed through slump flow, J-ring, and V-funnel tests. Water absorption and sorptivity tests were conducted to ensure the durability of the prepared mix. Further, impact tests were carried out on the prepared cylinder specimens to check the capability of the mix with the non-metallic hybrid combination. The main objective here was to check whether a high-strength durable SCC could be achieved using non-metallic fibres and natural fibres. From the obtained experimental results, it was observed that 15% alccofine as a partial substitute to the cement with the addition of 0.5% of abaca fibre and 2% of polypropylene fibre to SCC performed better than the control SCC.
  •  
5.
  •  
6.
  • Abram, Nerilie J., et al. (författare)
  • Early onset of industrial-era warming across the oceans and continents
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 411-418
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-ad 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.
  •  
7.
  •  
8.
  • Mansouri, Kamel, et al. (författare)
  • CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
  • 2020
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
  •  
9.
  • Rizzo, G., et al. (författare)
  • The predictive power of brain mRNA mappings for in vivo protein density: a positron emission tomography correlation study
  • 2014
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 34:5, s. 827-835
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial efforts are being spent on postmortem mRNA transcription mapping on the assumption that in vivo protein distribution can be predicted from such data. We tested this assumption by comparing mRNA transcription maps from the Allen Human Brain Atlas with reference protein concentration maps acquired with positron emission tomography (PET) in two representative systems of neurotransmission (opioid and serotoninergic). We found a tight correlation between mRNA expression and specific binding with 5-HT1A receptors measured with PET, but for opioid receptors, the correlation was weak. The discrepancy can be explained by differences in expression regulation between the two systems: transcriptional mechanisms dominate the regulation in the serotoninergic system, whereas in the opioid system proteins are further modulated after transcription. We conclude that mRNA information can be exploited for systems where translational mechanisms predominantly regulate expression. Where posttranscriptional mechanisms are important, mRNA data have to be interpreted with caution. The methodology developed here can be used for probing assumptions about the relationship of mRNA and protein in multiple neurotransmission systems.
  •  
10.
  • Selvaraj, Karthik, et al. (författare)
  • Cytotoxic unsaturated electrophilic compounds commonly target the ubiquitin proteasome system
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of natural products have been advocated as anticancer agents. Many of these compounds contain functional groups characterized by chemical reactivity. It is not clear whether distinct mechanisms of action can be attributed to such compounds. We used a chemical library screening approach to demonstrate that a substantial fraction (similar to 20%) of cytotoxic synthetic compounds containing Michael acceptor groups inhibit proteasome substrate processing and induce a cellular response characteristic of proteasome inhibition. Biochemical and structural analyses showed binding to and inhibition of proteasome-associated cysteine deubiquitinases, in particular ubiquitin specific peptidase 14 (USP14). The results suggested that compounds bind to a crevice close to the USP14 active site with modest affinity, followed by covalent binding. A subset of compounds was identified where cell death induction was closely associated with proteasome inhibition and that showed significant antineoplastic activity in a zebrafish embryo model. These findings suggest that proteasome inhibition is a relatively common mode of action by cytotoxic compounds containing Michael acceptor groups and help to explain previous reports on the antineoplastic effects of natural products containing such functional groups.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 11

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy