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.

Prevention and optimal management of sarcopenia: a review of combined exercise and nutrition interventions to improve muscle outcomes in older people.

Abstract: The growing recognition of sarcopenia, the age-related loss of skeletal muscle mass and function, has highlighted the need to understand more about its etiology. Declines in muscle mass and strength are expected aspects of aging, but there is significant variability between individuals in rates of loss. Although some of these differences can be explained by fixed factors, such as sex, much of the remaining variation is unexplained. This has led to increasing interest in the influence of adult lifestyle, particularly in the effects of modifiable factors such as physical activity and diet, and in identifying intervention opportunities both to prevent and manage sarcopenia. A number of trials have examined the separate effects of increased exercise or dietary supplementation on muscle mass and physical performance of older adults, but less is known about the extent to which benefits of exercise training could be enhanced when these interventions are combined. In a comprehensive review of the literature, we consider 17 studies of older adults (≥65 years) in which combined nutrition and exercise interventions were used to increase muscle strength and/or mass, and achieve improvements in physical performance. The studies were diverse in terms of the participants included (nutritional status, degree of physical frailty), supplementation strategies (differences in nutrients, doses), exercise training (type, frequency), as well as design (duration, setting). The main message is that enhanced benefits of exercise training, when combined with dietary supplementation, have been shown in some trials – indicating potential for future interventions, but that existing evidence is inconsistent. Further studies are needed, particularly of exercise training combined with dietary strategies that increase intakes of a range of nutrients, as well as bioactive non-nutrients, to provide the evidence on which public health and clinical recommendations can be based.

Social isolation and loneliness as risk factors for the progression of frailty: the English Longitudinal Study of Ageing.

Abstract: Background: loneliness and social isolation have been associated with mortality and with functional decline in older people. We investigated whether loneliness or social isolation are associated with progression of frailty. Methods: participants were 2817 people aged ≥60 from the English Longitudinal Study of Ageing. Loneliness was assessed at Wave 2 using the Revised UCLA scale (short version). A social isolation score at Wave 2 was derived from data on living alone, frequency of contact with friends, family and children, and participation in social organizations. Frailty was assessed by the Fried phenotype of physical frailty at Waves 2 and 4, and by a frailty index at Waves 2-5. Results: high levels of loneliness were associated with an increased risk of becoming physically frail or pre-frail around 4 years later: relative risk ratios (95% CI), adjusted for age, sex, level of frailty and other potential confounding factors at baseline were 1.74 (1.29, 2.34) for pre-frailty, and 1.85 (1.14, 2.99) for frailty. High levels of loneliness were not associated with change in the frailty index—a broadly-based measure of general condition--over a mean period of 6 years. In the sample as a whole, there was no association between social isolation and risk of becoming physically frail or pre-frail, but high social isolation was associated with increased risk of becoming physically frail in men. Social isolation was not associated with change in the frailty index. Conclusions: older people who experience high levels of loneliness are at increased risk of becoming physically frail.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

Abstract: Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

Abstract: Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.

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.