Identifying ambulatory advanced heart failure patients at high risk for death, LVAD or transplant at 1-year: How did the revival eligibility criteria perform?

Purpose: Identifying ambulatory advanced heart failurepatients who are at high risk for receiving an LVAD, a transplant or death is important in appropriately guiding clinical care, and in selecting patients for clinical trials. We evaluated the REVIVAL Registry inclusion criteria to determine their ability to identify patients who experienced any of these events within 1 year of enrollment. Methods: REVIVAL is a 400 patient, 21 center registry of patients with ambulatory advanced heart failure. Exclusion criteriaapproximated thoseof VAD clinical trials. Patients were eligible for inclusion if they met any of eight high riskcharacteristics (first 8 rows of Table) or if they had ≥ 2 HF hospitalizations in the prior year. As clinically indicated testing was utilized for inclusion, data were not available for all subjects for each criterion. Sensitivity, specificity, positive and negative predictive values were determined foreach inclusion criterion and for selected combinations Results: At 12 months, 359 evaluable subjects experienced 46 LVADs, 20 transplants and 29 deaths for a total of 95 events (26%). Competing outcome curves are shown in theFigure and test performance in the Table Conclusion: Theuse of multiple inclusion criteria applied to only clinically available information allowed identification of a high risksample of ambulatory advanced heart failure patients with a 26% event rate at 1 year. These findings can inform theselection of patients for future clinical trials in ambulatoryadvanced heart failure (Figure presented)

A minimal CENP-A core is required for nucleation and maintenance of a functional human centromere

Chromatin clusters containing CENP-A, a histone H3 variant, are found in centromeres of multicellular eukaryotes. This study examines the ability of alpha-satellite (alphoid) DNA arrays in different lengths to nucleate CENP-A chromatin and form functional kinetochores de novo. Kinetochore assembly was followed by measuring human artificial chromosome formation in cultured human cells and by chromatin immunoprecipitation analysis. The results showed that both the length of alphoid DNA arrays and the density of CENP-B boxes had a strong impact on nucleation, spreading and/or maintenance of CENP-A chromatin, and formation of functional kinetochores. These effects are attributed to a change in the dynamic balance between assembly of chromatin containing trimethyl histone H3-K9 and chromatin containing CENP-A/C. The data presented here suggest that a functional minimum core stably maintained on 30–70 kb alphoid DNA arrays represents an epigenetic memory of centromeric chromatin

”Om jag kan lämna 75 % av min kultur så måste Finland acceptera 25 % av min” : en narrativ studie av invandrares syn på integreringen till ett nytt samhälle

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries