Prostate cancer genomics: can we distinguish between indolent and fatal disease using genetic markers?

Prostate cancer is one of the most heritable cancers in men, and recent genome-wide association studies have revealed numerous genetic variants associated with disease. The risk variants identified using case-control designs that compared unaffected individuals with all types of patients with prostate cancer show little or no ability to discriminate between indolent and fatal forms of this disease. This suggests different genetic components are involved in the initiation as compared with the prognosis of prostate cancer. Future studies contrasting patients with more and less aggressive disease, and exploring association with disease progression and prognosis, should be more effective in detecting genetic risk factors for prostate cancer outcome

Effects of in-company quality awards on organizational performance

The relationship between total quality management (TQM) practices and improved performance has been frequently discussed in the literature. In this paper, the costs and the effects of in-company quality awards on performance are discussed and analysed. The paper covers a survey of Swedish companies that use or have used in-company quality awards to stimulate TQM efforts and thereby to improve performance. The study cannot show any strong evidence of improved performance for units that applied for the in-company quality award. However, in contrast to units that have not applied, some units that have applied for the in-company quality award considered that the results related to performance have improved greatly. One large positive effect perceived by the participating units was increased customer orientation while the largest costs were put on the description of activities and the improvement work itself

Разработка гидропривода транспортёра и мотовила жатки самоходной косилки КС-100

We propose a novel method for iterative learning of point correspondences between image sequences. Points moving on surfaces in 3D space are projected into two images. Given a point in either view, the considered problem is to determine the corresponding location in the other view. The geometry and distortions of the projections are unknown as is the shape of the surface. Given several pairs of point-sets but no access to the 3D scene, correspondence mappings can be found by excessive global optimization or by the fundamental matrix if a perspective projective model is assumed. However, an iterative solution on sequences of point-set pairs with general imaging geometry is preferable. We derive such a method that optimizes the mapping based on Neyman's chi-square divergence between the densities representing the uncertainties of the estimated and the actual locations. The densities are represented as channel vectors computed with a basis function approach. The mapping between these vectors is updated with each new pair of images such that fast convergence and high accuracy are achieved. The resulting algorithm runs in real-time and is superior to state-of-the-art methods in terms of convergence and accuracy in a number of experiments.funding agencies|EC|215078247947|ELLIIT||Strategic Area for ICT research||CADICS||Swedish Government||Swedish Research Council||CUAS||FOCUS||Swedish Foundation for Strategic Research||DIPLECSGARNICSELLIITETTCUASFOCUSCADIC

Inherited DNA repair gene mutations in men with lethal prostate cancer

Germline variants in DNA repair genes are associated with aggressive prostate cancer (PrCa). The aim of this study was to characterize germline variants in DNA repair genes associated with lethal PrCa in Finnish and Swedish populations. Whole-exome sequencing was performed for 122 lethal and 60 unselected PrCa cases. Among the lethal cases, a total of 16 potentially damaging protein-truncating variants in DNA repair genes were identified in 15 men (12.3%). Mutations were found in six genes with CHEK2 (4.1%) and ATM (3.3%) being most frequently mutated. Overall, the carrier rate of truncating variants in DNA repair genes among men with lethal PrCa significantly exceeded the carrier rate of 0% in 60 unselected PrCa cases (p = 0.030), and the prevalence of 1.6% (p < 0.001) and 5.4% (p = 0.040) in Swedish and Finnish population controls from the Exome Aggregation Consortium. No significant difference in carrier rate of potentially damaging nonsynonymous single nucleotide variants between lethal and unselected PrCa cases was observed (p = 0.123). We confirm that DNA repair genes are strongly associated with lethal PrCa in Sweden and Finland and highlight the importance of population-specific assessment of variants contributing to PrCa aggressiveness.</p

Neuroinflammatory markers associate with cognitive decline after major surgery:Findings of an explorative study

OBJECTIVE Long‐term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long‐term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long‐term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long‐term cognitive decline at 3 months postsurgery. METHODS Serum and CSF biomarkers of inflammation and blood–brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. RESULTS Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48‐hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long‐term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long‐term cognitive decline at 3 months. Patients both with and patients without long‐term cognitive decline showed early transient increases of the astroglial biomarkers S‐100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). INTERPRETATION Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long‐term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. ANN NEUROL 202

Post hoc Analysis for Detecting Individual Rare Variant Risk Associations Using Probit Regression Bayesian Variable Selection Methods in Case-Control Sequencing Studies

Rare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single-marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden-type approaches attempt to identify aggregation of RVs across case-control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large-scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway-level RV analysis results from a prostate cancer (PC) risk case-control sequencing study. Finally, we discuss potential extensions and future directions of this work