Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Adaptive Rejection Metropolis Sampling Within Gibbs Sampling

Abstract: Gibbs sampling is a powerful technique for statistical inference. It involves little more than sampling from full conditional distributions, which can be both complex and computationally expensive to evaluate. Gilks and Wild have shown that in practice full conditionals are often log‐concave, and they proposed a method of adaptive rejection sampling for efficiently sampling from univariate log‐concave distributions. In this paper, to deal with non‐log‐concave full conditional distributions, we generalize adaptive rejection sampling to include a Hastings‐Metropolis algorithm step. One important field of application in which statistical models may lead to non‐log‐concave full conditionals is population pharmacokinetics. Here, the relationship between drug dose and blood or plasma concentration in a group of patients typically is modelled by using nonlinear mixed effects models. Often, the data used for analysis are routinely collected hospital measurements, which tend to be noisy and irregular. Consequently, a robust (t‐distributed) error structure is appropriate to account for outlying observations and/or patients. We propose a robust nonlinear full probability model for population pharmacokinetic data. We demonstrate that our method enables Bayesian inference for this model, through an analysis of antibiotic administration in new‐born babies.

Reduced Thirst after Water Deprivation in Healthy Elderly Men

Abstract: To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin.

Senescence and aging: Causes, consequences, and therapeutic avenues

Abstract: Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding the biological basis of aging, research suggests that targeting the aging process itself could ameliorate many age-related pathologies. Senescence is a cellular response characterized by a stable growth arrest and other phenotypic alterations that include a proinflammatory secretome. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. However, senescence has also been implicated as a major cause of age-related disease. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends life span and improves health span. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.

Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial

Abstract: Summary Background Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. Methods The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] ≥34 kg/m 2 in men, and ≥38 kg/m 2 in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99·9% and the median follow-up time was 10·9 years (range 0–18·1 years). Findings Bariatric surgery resulted in a sustained mean weight reduction of 19·9 kg (SD 15·6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1·3 kg (SD 13·7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0·67, 95% CI 0·53–0·85, p=0·0009). The sex–treatment interaction p value was 0·054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0·58, 0·44–0·77; p=0·0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0·97, 0·62–1·52; p=0·90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. Interpretation Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. Funding Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.