Genome-Wide Association Data Reveal a Global Map of Genetic Interactions among Protein Complexes

This work demonstrates how gene association studies can be analyzed to map a global landscape of genetic interactions among protein complexes and pathways. Despite the immense potential of gene association studies, they have been challenging to analyze because most traits are complex, involving the combined effect of mutations at many different genes. Due to lack of statistical power, only the strongest single markers are typically identified. Here, we present an integrative approach that greatly increases power through marker clustering and projection of marker interactions within and across protein complexes. Applied to a recent gene association study in yeast, this approach identifies 2,023 genetic interactions which map to 208 functional interactions among protein complexes. We show that such interactions are analogous to interactions derived through reverse genetic screens and that they provide coverage in areas not yet tested by reverse genetic analysis. This work has the potential to transform gene association studies, by elevating the analysis from the level of individual markers to global maps of genetic interactions. As proof of principle, we use synthetic genetic screens to confirm numerous novel genetic interactions for the INO80 chromatin remodeling complex

Hospitalization-associated disability in older adults with valvular heart disease: incidence, risk factors and its association with care processes

The aim of this study was to determine the incidence and recovery of hospitalisation-associated disability (HAD), the associated risk factors, and the link with care processes in patients aged 70 years or older hospitalised with valvular heart disease (VHD).; Prospective cohort study performed on the cardiology and cardiac surgery units of University Hospitals Leuven, Belgium. HAD was defined as the loss of independence to complete one of the Activities of Daily Living (ADLs) between hospital admission and discharge. Recovery of HAD at 30 days post hospital discharge was achieved when patients recovered their baseline ADL status (2 weeks before hospital admission) (ClinicalTrials.gov: NCT02572999).; Eighty patients were enrolled in the study, 77 completed the assessment at discharge and 62 responded at 30 days follow-up. Forty patients (51.9%) developed HAD; 18 of them (45.0%) recovered their baseline ADL status. The risk of HAD increased when patients were physically restrained (relative risk (RR) 1.73, 95% confidence interval (CI) 1.20-2.49), had indwelling catheters (RR 1.80, 95% CI 0.85-3.80) and received preventive pressure ulcer measures (RR 1.71, 95% CI 1.07-2.74). Patients with HAD had longer hospital stays (+3 days, p = .011) and longer use of indwelling catheters (+2 days, p = .024).; Half of the older adults with VHD developed HAD. The results indicate a potential association between HAD and care processes, which could be used as quality measures and intervention targets. Validation in larger cohort studies is recommended

World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease: an evidence-based guideline

Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease (RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the development of new international echocardiographic guidelines that address the full spectrum of the rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach\ud to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation\ud echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave,and color-Doppler echocardiography: 'definite RHD', 'borderline RHD', and 'normal'. Four subcategories of 'definite RHD' and three subcategories of 'borderline RHD' exist, to reflect the various disease patterns. The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However, important unanswered questions remain about the importance of subclinical disease (borderline or definite RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing screening programs. These standardized criteria will help enable new studies to be designed to evaluate the role of echocardiographic screening in RHD control