SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Powell John) ;lar1:(lu)"

Sökning: WFRF:(Powell John) > Lunds universitet

  • Resultat 1-9 av 9
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
  •  
2.
  • Yi, Chuixiang, et al. (författare)
  • Climate control of terrestrial carbon exchange across biomes and continents
  • 2010
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
  •  
3.
  • Denton, Christopher P., et al. (författare)
  • Recombinant human anti-transforming growth factor beta 1 antibody therapy in systemic sclerosis - A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192
  • 2007
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:1, s. 323-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta 1 (TGF beta 1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Methods. Patients with SSc duration of < 18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mglkg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGF beta 1 and TGF beta 2. Results. Forty-five patients were enrolled. There was significant morbidity and mortality, including I death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). Conclusion. We report the first evaluation of a systemically administered and repeatedly dosed anti-TGF beta 1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.
  •  
4.
  • Guerreiro, Rita, et al. (författare)
  • Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
  • 2016
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 38, s. 7-214
  • Tidskriftsartikel (refereegranskat)abstract
    • The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
  •  
5.
  • Yang, Jian, et al. (författare)
  • FTO genotype is associated with phenotypic variability of body mass index
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
  • Tidskriftsartikel (refereegranskat)abstract
    • There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
  •  
6.
  • Clayton, Emma L., et al. (författare)
  • Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation
  • 2017
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:5, s. 873-887
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.
  •  
7.
  • Helgadottir, Anna, et al. (författare)
  • Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
  • 2012
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
  •  
8.
  • Iversen, Katherine R., et al. (författare)
  • Decentralization and Regionalization of Surgical Care: A Review of Evidence for the Optimal Distribution of Surgical Services in Low- and Middle-Income Countries
  • 2019
  • Ingår i: International Journal of Health Policy and Management. - 2322-5939. ; 8:9, s. 521-537
  • Forskningsöversikt (refereegranskat)abstract
    • Background: While recommendations for the optimal distribution of surgical services in high-income countries (HICs) exist, it is unclear how these translate to resource-limited settings. Given the significant shortage and maldistribution of surgical workforce and infrastructure in many low- and middle-income countries (LMICs), the optimal role of decentralization versus regionalization (centralization) of surgical care is unknown. The aim of this study is to review evidence around interventions aimed at redistributing surgical services in LMICs, to guide recommendations for the ideal organization of surgical services.Methods: A narrative-based literature review was conducted to answer this question. Studies published in English between 1997 and 2017 in PubMed, describing interventions to decentralize or regionalize a surgical procedure in a LMIC, were included. Procedures were selected using the Disease Control Priorities’ (DCP3) Essential Surgery Package list. Intervention themes and outcomes were analyzed using a narrative, thematic synthesis approach. Primary outcomes included mortality, complications, and patient satisfaction. Secondary outcomes included input measures: workforce and infrastructure, and process measures: facility-based care, surgical volume, and referral rates.Results: Thirty-five studies were included. Nine (33%) of the 27 studies describing decentralization showed an improvement in primary outcomes. The procedures associated with improved outcomes after decentralization included most obstetric, gynecological, and family planning services as well as some minor general surgery procedures. Out of 8 studies on regionalization (centralization), improved outcomes were shown for trauma care in one study and cataract extraction in one study.Conclusion: Interventions aimed at decentralizing obstetric care to the district hospital and health center levels have resulted in mortality benefits in several countries. However, more evidence is needed to link service distribution to patient outcomes in order to provide recommendations for the optimal organization of other surgical procedures in LMICs. Considerations for the optimal distribution of surgical procedures should include the acuity of the condition for which the procedure is indicated, anticipated case volume, and required level of technical skills, resources, and infrastructure. These attributes should be considered within the context of each country.
  •  
9.
  • Martini, Paolo G. V., et al. (författare)
  • Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases
  • 2010
  • Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-9 av 9
Typ av publikation
tidskriftsartikel (8)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (9)
Författare/redaktör
Hamsten, Anders (3)
Thorleifsson, Gudmar (3)
Thorsteinsdottir, Un ... (3)
Stefansson, Kari (3)
Groop, Leif (2)
Berndt, Sonja I (2)
visa fler...
Chanock, Stephen J (2)
Campbell, Harry (2)
Rudan, Igor (2)
Ohlsson, Claes, 1965 (2)
Strachan, David P (2)
North, Kari E. (2)
Wareham, Nicholas J. (2)
Hall, Per (2)
McCarthy, Mark I (2)
Tregouet, David Alex ... (2)
Ridker, Paul M. (2)
Chasman, Daniel I. (2)
Demirkan, Ayse (2)
van Duijn, Cornelia ... (2)
Rose, Lynda M (2)
Boehnke, Michael (2)
Mohlke, Karen L (2)
Verweij, Niek (2)
Shuldiner, Alan R. (2)
Abecasis, Goncalo R. (2)
Powell, John (2)
Mangino, Massimo (2)
Willemsen, Gonneke (2)
Oostra, Ben A. (2)
Madden, Pamela A. F. (2)
Peters, Annette (2)
Nyholt, Dale R. (2)
Martin, Nicholas G. (2)
Spector, Tim D. (2)
Samani, Nilesh J. (2)
Jarvelin, Marjo-Riit ... (2)
de Faire, Ulf (2)
Kiemeney, Lambertus ... (2)
Mahajan, Anubha (2)
Luan, Jian'an (2)
Metspalu, Andres (2)
Farrall, Martin (2)
Hicks, Andrew A. (2)
Pramstaller, Peter P ... (2)
Wright, Alan F. (2)
Wilson, James F. (2)
Jacobs, Kevin B (2)
Nalls, Michael A. (2)
Montgomery, Grant W. (2)
visa färre...
Lärosäte
Göteborgs universitet (1)
Umeå universitet (1)
Uppsala universitet (1)
Karolinska Institutet (1)
Sveriges Lantbruksuniversitet (1)
Språk
Engelska (9)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (8)
Naturvetenskap (1)

År

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