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Sökning: WFRF:(Hughes Gareth)

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1.
  • Aad, G., et al. (författare)
  • 2011
  • swepub:Mat__t (refereegranskat)
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2.
  • Blagrove, Marcus S. C., et al. (författare)
  • Potential for Zika virus transmission by mosquitoes in temperate climates
  • 2020
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 287:1930
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosquito-borne Zika virus (ZIKV) transmission has almost exclusively been detected in the tropics despite the distributions of its primary vectors extending farther into temperate regions. Therefore, it is unknown whether ZIKV's range has reached a temperature-dependent limit, or if it can spread into temperate climates. Using field-collected mosquitoes for biological relevance, we found that two common temperate mosquito species,Aedes albopictusandOchlerotatus detritus, were competent for ZIKV. We orally exposed mosquitoes to ZIKV and held them at between 17 and 31 degrees C, estimated the time required for mosquitoes to become infectious, and applied these data to a ZIKV spatial risk model. We identified a minimum temperature threshold for the transmission of ZIKV by mosquitoes between 17 and 19 degrees C. Using these data, we generated standardized basic reproduction numberR(0)-based risk maps and we derived estimates for the length of the transmission season for recent and future climate conditions. Our standardizedR(0)-based risk maps show potential risk of ZIKV transmission beyond the current observed range in southern USA, southern China and southern European countries. Transmission risk is simulated to increase over southern and Eastern Europe, northern USA and temperate regions of Asia (northern China, southern Japan) in future climate scenarios.
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3.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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4.
  • Devin, James L, et al. (författare)
  • Cardiorespiratory Fitness and Body Composition Responses to Different Intensities and Frequencies of Exercise Training in Colorectal Cancer Survivors.
  • 2018
  • Ingår i: Clinical colorectal cancer. - : Elsevier BV. - 1938-0674 .- 1533-0028. ; 17:2, s. e269-e279
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Deteriorations in cardiorespiratory fitness (V˙o2peak) and body composition are associated with poor prognosis after colorectal cancer treatment. However, the optimal intensity and frequency of aerobic exercise training to improve these outcomes in colorectal cancer survivors is unknown.PATIENTS AND METHODS: This trial compared 8 weeks of moderate-intensity continuous exercise (MICE; 50 minutes; 70% peak heart rate [HRpeak]; 24 sessions), with high-intensity interval exercise (HIIE; 4 × 4 minutes; 85%-95% HRpeak) at an equivalent (HIIE; 24 sessions) and tapered frequency (HIIE-T; 16 sessions) on V˙o2peak and on lean and fat mass, measured at baseline, 4, 8, and 12 weeks.RESULTS: Increases in V˙o2peak were significantly greater after both 4 (+3.0 mL·kg-1·min-1, P = .008) and 8 (+2.3 mL·kg-1·min-1, P = .049) weeks of HIIE compared to MICE. After 8 weeks, there was a significantly greater reduction in fat mass after HIIE compared to MICE (-0.7 kg, P = .038). Four weeks after training, the HIIE group maintained elevated V˙o2peak (+3.3 mL·kg-1·min-1, P = .006) and reduced fat mass (-0.7 kg, P = .045) compared to the MICE group, with V˙o2peak in the HIIE-T also being superior to the MICE group (+2.8 mL·kg-1·min-1, P = .013).CONCLUSION: Compared to MICE, HIIE promotes superior improvements and short-term maintenance of V˙o2peak and fat mass improvements. HIIE training at a reduced frequency also promotes maintainable cardiorespiratory fitness improvements. In addition to promoting accelerated and superior benefits to the current aerobic exercise guidelines, HIIE promotes clinically relevant improvements even with a substantial reduction in exercise training and for a period after withdrawal.
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6.
  • Devin, James L, et al. (författare)
  • The influence of high-intensity compared with moderate-intensity exercise training on cardiorespiratory fitness and body composition in colorectal cancer survivors : a randomised controlled trial.
  • 2016
  • Ingår i: Journal of cancer survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 10:3, s. 467-479
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Following colorectal cancer diagnosis and anti-cancer therapy, declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality. There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes. This study compared 4 weeks of moderate-intensity exercise (MIE) and high-intensity exercise (HIE) training on peak oxygen consumption (V̇O2peak) and body composition in colorectal cancer survivors.METHODS: Forty seven post-treatment colorectal cancer survivors (HIE = 27 months post-treatment; MIE = 38 months post-treatment) were randomised to either HIE [85-95 % peak heart rate (HRpeak)] or MIE (70 % HRpeak) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks.RESULTS: HIE was superior to MIE in improving absolute (p = 0.016) and relative (p = 0.021) V̇O2peak. Absolute (+0.28 L.min(-1), p < 0.001) and relative (+3.5 ml.kg(-1).min(-1), p < 0.001) V̇O2 peak were increased in the HIE group but not the MIE group following training. HIE led to significant increases in lean mass (+0.72 kg, p = 0.002) and decreases in fat mass (-0.74 kg, p < 0.001) and fat percentage (-1.0 %, p < 0.001), whereas no changes were observed for the MIE group. There were no severe adverse events.CONCLUSIONS: In response to short-term training, HIE is a safe, feasible and efficacious intervention that offers clinically meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors.IMPLICATIONS FOR CANCER SURVIVORS: HIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment.
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8.
  • Kurilshikov, Alexander, et al. (författare)
  • Large-scale association analyses identify host factors influencing human gut microbiome composition
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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9.
  • Kvols, Larry K, et al. (författare)
  • Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR : results from a phase II study
  • 2012
  • Ingår i: Endocrine-related cancer. - 1479-6821. ; 19:5, s. 657-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst(1,2,3)) and sst(5). Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 μg twice daily (bid), escalated to a maximum dose of 1200 μg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 μg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 μg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.
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10.
  • McCaddon, Andrew, et al. (författare)
  • Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease
  • 2004
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Isoforms of the vitamin B<sub>12</sub> carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer’s disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox’s F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox’s F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.
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