Using the Pareto principle in genome-wide breeding value estimation

Genome-wide breeding value (GWEBV) estimation methods can be classified based on the prior distribution assumptions of marker effects. Genome-wide BLUP methods assume a normal prior distribution for all markers with a constant variance, and are computationally fast. In Bayesian methods, more flexible prior distributions of SNP effects are applied that allow for very large SNP effects although most are small or even zero, but these prior distributions are often also computationally demanding as they rely on Monte Carlo Markov chain sampling. In this study, we adopted the Pareto principle to weight available marker loci, i.e., we consider that x% of the loci explain (100 - x)% of the total genetic variance. Assuming this principle, it is also possible to define the variances of the prior distribution of the 'big' and 'small' SNP. The relatively few large SNP explain a large proportion of the genetic variance and the majority of the SNP show small effects and explain a minor proportion of the genetic variance. We name this method MixP, where the prior distribution is a mixture of two normal distributions, i.e. one with a big variance and one with a small variance. Simulation results, using a real Norwegian Red cattle pedigree, show that MixP is at least as accurate as the other methods in all studied cases. This method also reduces the hyper-parameters of the prior distribution from 2 (proportion and variance of SNP with big effects) to 1 (proportion of SNP with big effects), assuming the overall genetic variance is known. The mixture of normal distribution prior made it possible to solve the equations iteratively, which greatly reduced computation loads by two orders of magnitude. In the era of marker density reaching million(s) and whole-genome sequence data, MixP provides a computationally feasible Bayesian method of analysis

Designing a multifaceted quality improvement intervention in primary care in a country where general practice is seeking recognition: the case of Cyprus

<p>Abstract</p> <p>Background</p> <p>Quality Improvement Interventions require significant financial investments, and therefore demand careful consideration in their design in order to maximize potential benefits. In this correspondence we present the methodological approach of a multifaceted quality improvement intervention aiming to improve quality of care in primary care, properly tailored for a country such as Cyprus where general practice is currently seeking recognition.</p> <p>Methods</p> <p>Our methodological approach was focused on the design of an open label, community-based intervention controlled trial using all patients from two urban and two rural public primary care centers diagnosed with hypertension and type II diabetes mellitus. The design of our intervention was grounded on a strong theoretical framework that included the Unified Theory of Acceptance and Use of Technology, and the Chronic Care Model, which synthesize evidence-based system changes in accordance with the Theory of Planned Behavior and the Theory of Reasoned Action. The primary outcome measure was improvement in the quality of care for two chronic diseases evaluated through specific clinical indicators, as well as the patient satisfaction assessed by the EUROPEP questionnaire and additional personal interviews.</p> <p>Results</p> <p>We designed a multifaceted quality improvement intervention model, supported by a varying degree of scientific evidence, tailored to local needs and specific country characteristics. Overall, the main components of the intervention were the development and adoption of an electronic medical record and the introduction of clinical guidelines for the management of the targeted chronic diseases facilitated by the necessary model of organizational changes.</p> <p>Conclusion</p> <p>Health planners and policy makers need to be aware of the potential use of certain theoretical models and applied methodology as well as inexpensive tools that may be suitably tailored to the local needs, in order to effectively design quality improvement interventions in primary care settings.</p

Outlining a new collaborative business model as a result of the green Building Information Modelling impact in the AEC supply chain

BIM (Building Information Modelling) technological push has enabled to integrate the design/construction outcomes of 3D-CAD along the product/service AEC (Architecture, Engineering and Construction) SC (supply chain) through an intelligent DMS (Data Management System) based on standard and interoperable data formats. The proposed end-to-end approach overcomes a typical AEC gap, enables the operationalisation of the sustainable/green building LCA (Life Cycle Assessment) and puts together new collaborative relationships with the owner, among SC stakeholders and with new forms of BIM procurement. The outlined collaborative business model is based on the Quality Control and Assurance framework and provides conceptual consistency to the reintroduction of the owner concerns/satisfaction in the SC, as well as enables consistent and accountable relationships between (smart)materials procurement and building specification. An expert’s focus group carried out a preliminary check of the model’s interest/applicability, resulting in recommendations for its further detailing and for propositions development into a systematic enquiring process.info:eu-repo/semantics/acceptedVersio

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC