Cyrus Cooper

Bio: Cyrus Cooper is an academic researcher from Southampton General Hospital. The author has contributed to research in topics: Population & Osteoporosis. The author has an hindex of 204, co-authored 1869 publications receiving 206782 citations. Previous affiliations of Cyrus Cooper include University of Oxford & University of York.

DNA methylation of Th2 lineage determination genes at birth is associated with allergic outcomes in childhood.

Abstract: Background There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes. Objective and Methods To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n=696) who were later assessed for asthma, atopic eczema and atopy. Results We found that higher methylation of GATA3 CpGs -2211/-2209 at birth was associated with a reduced risk of asthma at ages 3 (median ratio [median methylation in asthma group/median methylation in non-asthma group] =0.74, p=0.006) and 6 (median ratio 0.90, p=0.048) years. Furthermore, we demonstrated that the GATA3 CpG loci associated with later risk of asthma lie within a NF-κB binding site, and that methylation here blocks transcription factor binding to the GATA3 promoter in the Human Jurkat T cell line. Associations between umbilical cord methylation of CpG loci within IL-4R with atopic eczema at 12 months (median ratio 1.02, p=0.028), and TBET with atopy (median ratio 0.98, p=0.017) at 6-7 years of age were also observed. Conclusions and Clinical Relevance Our findings provides further evidence of a developmental contribution to the risk of later allergic disorders, and suggests that involvement of epigenetic mechanisms in childhood asthma is already demonstrable at birth. This article is protected by copyright. All rights reserved.

Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor.

Abstract: Objective To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR). Design and patients The Longitudinal Ageing Study Amsterdam (LASA), a population-based cohort study in older men and women. Measurements Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self-report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858). Results Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = -0.135, P = 0.04). No significant associations in men were found. Female 9beta G-allele carriers had 50.2 nmol/l lower cortisol and 1.2 lower free cortisol levels than AA homozygotes [P = 0.01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54.8 nmol/l higher cortisol levels than C-carriers (P = 0.03). In the total population, BclI GG homozygotes had 0.05 g/cm(2) lower trochanteric region BMD (P = 0.03). For the other GR gene polymorphisms, no significant associations were found. Conclusions Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population.

Grip strength among community-dwelling older people predicts hospital admission during the following decade.

Abstract: Background: lower grip strength on admission to hospital is known to be associated with longer stay, but the link between customary grip and risk of future admission is less clear. Objective: to compare grip strength with subsequent risk of hospital admission among community-dwelling older people in a UK setting. Design: cohort study with linked administrative data. Setting: Hertfordshire, UK. Subjects: a total of 2,997 community-dwelling men and women aged 59–73 years at baseline. Methods: the Hertfordshire Cohort Study (HCS) participants completed a baseline assessment between 1998 and 2004, during which grip strength was measured. Hospital Episode Statistics and mortality data to March 2010 were linked with the HCS database. Statistical models were used to investigate the association of grip strength with subsequent elective, emergency and long-stay hospitalisation and readmission. Results: there was a statistically significant negative association between grip strength and all classes of admission in women [unadjusted hazard ratio per standard deviation (SD) decrease in grip strength for: any admission/death 1.10 (95% CI: 1.06, 1.14), elective admission/death 1.09 (95% CI: 1.05, 1.13), emergency admission/death 1.21 (95% CI: 1.13, 1.31), long-stay admission/death 1.22 (95% CI: 1.13, 1.32) and unadjusted relative risk per SD decrease in grip strength for 30-day readmission/death 1.30 (95% CI: 1.19, 1.43)]. These associations remained significant after adjustment for potential confounding factors (age, height, weight for height, smoking, alcohol, social class). In men, unadjusted rates for emergency admission/death, long-stay admission/death and readmission/death were significantly associated with grip strength; associations that similarly withstood adjustment. Conclusion: this study provides the first evidence that grip strength among community-dwelling men and women in the UK is associated with risk of hospital admission over the following decade

Excess mortality in osteoarthritis.

Abstract: Provides evidence for a unified approach to musculoskeletal ageing Osteoarthritis is the most common joint disorder worldwide. It comprises a group of overlapping disorders that may have different causes, but which result in joint failure subsequent to morphological changes in articular cartilage, subchondral bone, synovium, and other joint structures. Osteoarthritis typically affects the hands, knees, hips, spine, and feet.1 Although osteoarthritis can be defined pathologically, radiographically, or clinically, most epidemiological studies have relied upon radiographic features to characterise the disease. Radiographic features have a graded (although sometimes discordant) association with clinical features—joint pain and functional impairment—with notable disability arising from involvement of the knee and hip. The lifetime risk of osteoarthritis specific morbidity is about 25% for the hip2 and 45% for the knee,3 and the disorder is a major contributor to the 57 000 knee and 55 000 hip arthroplasties undertaken each year in the United Kingdom.4 In the linked study (doi:10.1136/bmj.d1165), Nuesch and colleagues assess all cause and disease specific mortality in patients with knee or hip osteoarthritis⇓.5 Zephyr/SPL In contrast to the well established morbidity attributable to osteoarthritis, relatively …

Hertfordshire sarcopenia study: design and methods.

Abstract: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms. One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study. The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Using Multivariate Statistics

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Vitamin D Deficiency

Abstract: Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.