Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data

Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, we demonstrate that this method is >50% more accurate at identifying functionally related protein pairs than previous approaches. Application to genes involved in yeast chromosome organization identifies a functional map of 91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly, we find that complexes that are enriched for aggravating genetic interactions (i.e., synthetic lethality) are more likely to contain essential genes, linking each of these interactions to an underlying mechanism. These results demonstrate the importance of both large-scale genetic and physical interaction data in mapping pathway architecture and function

The European influence on workers' compensation reform in the United States

Workers' compensation law in the United States is derived from European models of social insurance introduced in Germany and in England. These two concepts of workers' compensation are found today in the federal and state workers' compensation programs in the United States. All reform proposals in the United States are influenced by the European experience with workers' compensation. In 2006, a reform proposal termed the Public Health Model was made that would abolish the workers' compensation system, and in its place adopt a national disability insurance system for all injuries and illnesses. In the public health model, health and safety professionals would work primarily in public health agencies. The public health model eliminates the physician from any role other than that of privately consulting with the patient and offering advice solely to the patient. The Public Health Model is strongly influenced by the European success with physician consultation with industry and labor

Measuring macroscopic brain connections in vivo

Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means

FRAX provides robust fracture prediction regardless of socioeconomic status

The authors investigated the fracture risk assessment tool (FRAX) Canada calibration and discrimination according to income quintile in 51,327 Canadian women, with and without a competing mortality framework. The data shows that, under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of socioeconomic status (SES)

The contributions of first nations ethnicity, income, and delays in surgery on mortality post-fracture : a population-based analysis

Summary We examined the independent contributions of First Nations ethnicity and lower income to post-fracture mortality. A similar relative increase in mortality associated with fracture appears to translate into a larger absolute increase in post-fracture mortality for First Nations compared to non-First Nations peoples. Lower income also predicted increased mortality post-fracture.Introduction First Nations peoples have a greater risk of mortality than non-First Nations peoples. We examined the independent contributions of First Nations ethnicity and income to mortality post-fracture, and associations with time to surgery post-hip fracture.Methods Non-traumatic fracture cases and fracture-free controls were identified from population-based administrative data repositories for Manitoba, Canada (aged &ge;50 years). Populations were retrospectively matched for sex, age (within 5 years), First Nations ethnicity, and number of comorbidities. Differences in mortality post-fracture of hip, wrist, or spine, 1996&ndash;2004 (population 1, n&thinsp;=&thinsp;63,081), and the hip, 1987&ndash;2002(Population 2, n&thinsp;=&thinsp;41,211) were examined using Cox proportional hazards regression to model time to death. For hip fracture, logistic regression analyses were used to model the probability of death within 30 days and 1 year.Results Population 1: First Nations ethnicity was associated with an increased mortality risk of 30&ndash;53 % for each fracture type. Lower income was associated with an increased mortality risk of 18&ndash;26 %. Population 2: lower income predicted mortality overall (odds ratio (OR) 1.15, 95 % confidence interval (CI) 1.07&ndash;1.23) and for hip fracture cases (OR 1.18, 95%CI 1.05&ndash;1.32), as did older age, male sex, diabetes, and &gt;5 comorbidities (all p&thinsp;&le;&thinsp;0.01). Higher mortality was associated with pertrochanteric fracture (OR 1.14, 95 % CI 1.03&ndash;1.27), or surgery delay of 2&ndash;3 days (OR 1.34, 95 % CI 1.18&ndash;1.52) or &ge;4 days (OR 2.35, 95 % CI 2.07&ndash;2.67).Conclusion A larger absolute increase in mortality post-fracture was observed for First Nations compared to non-First Nations peoples. Lower income and surgery delay &gt;2 days predicted mortality post-fracture. These data have implications regarding prioritization of healthcare to ensure targeted, timely care for First Nations peoples and/or individuals with lower income.<br /