Genome-wide association and genomic selection in aquaculture

Recent advancements in genomic technologies have led to the discovery and application of DNA-markers [e.g. single nucleotide polymorphisms (SNPs)] for the genetic improvement of several aquaculture species. The identification of specific genomic regions associated with economically important traits, using, for example, genome-wide association studies (GWAS), has allowed the discovery and incorporation of markers linked to quantitative trait loci (QTL) into aquaculture breeding programs through marker-assisted selection (MAS). However, most of the traits of economic relevance are expected to be controlled by many QTLs, each one explaining only a small proportion of the genetic variation. For traits under polygenic control, prediction of the genetic merit of animals based on the sum of effects at positions across the entire genome (i.e. genomic estimated breeding values, GEBV, which are used for what has become known as genomic selection), has been demonstrated to speed the rate of genetic gain for several traits in aquaculture breeding. The aim of this review was to provide an overview of the development and application of genomic technologies in uncovering the genetic basis of complex traits and accelerating the genetic progress in aquaculture species, as well as providing future perspectives about the deployment of novel molecular technologies for selective breeding in coming years

Performance and Energy Trade-Offs for Parallel Applications on Heterogeneous Multi-Processing Systems

This work proposes a methodology to find performance and energy trade-offs for parallel applications running on Heterogeneous Multi-Processing systems with a single instruction-set architecture. These offer flexibility in the form of different core types and voltage and frequency pairings, defining a vast design space to explore. Therefore, for a given application, choosing a configuration that optimizes the performance and energy consumption is not straightforward. Our method proposes novel analytical models for performance and power consumption whose parameters can be fitted using only a few strategically sampled offline measurements. These models are then used to estimate an application’s performance and energy consumption for the whole configuration space. In turn, these offline predictions define the choice of estimated Pareto-optimal configurations of the model, which are used to inform the selection of the configuration that the application should be executed on. The methodology was validated on an ODROID-XU3 board for eight programs from the PARSEC Benchmark, Phoronix Test Suite and Rodinia applications. The generated Pareto-optimal configuration space represented a 99% reduction of the universe of all available configurations. Energy savings of up to 59.77%, 61.38% and 17.7% were observed when compared to the performance, ondemand and powersave Linux governors, respectively, with higher or similar performance

Facial nerve palsy following parotid gland surgery : A machine learning prediction outcome approach

Machine learning (ML)-based facial nerve injury (FNI) forecasting grounded on multicentric data has not been released up to now. Three distinct ML models, random forest (RF), K-nearest neighbor, and artificial neural network (ANN), for the prediction of FNI were evaluated in this mode. A retrospective, longitudinal, multicentric study was performed, including patients who went through parotid gland surgery for benign tumors at three different university hospitals. Seven hundred and thirty-six patients were included. The most compelling aspects related to risk escalation of FNI were as follows: (1) location, in the mid-portion of the gland, near to or above the main trunk of the facial nerve and at the top part, over the frontal or the orbital branch of the facial nerve; (2) tumor volume in the anteroposterior axis; (3) the necessity to simultaneously dissect more than one level; and (4) the requirement of an extended resection compared to a lesser extended resection. By contrast, in accordance with the ML analysis, the size of the tumor (>3 cm), as well as gender and age did not result in a determining favor in relation to the risk of FNI. The findings of this research conclude that ML models such as RF and ANN may serve evidence-based predictions from multicentric data regarding the risk of FNI. Along with the advent of ML technology, an improvement of the information regarding the potential risks of FNI associated with patients before each procedure may be achieved with the implementation of clinical, radiological, histological, and/or cytological data

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

CD8+ T Cells and IFN-γ Mediate the Time-Dependent Accumulation of Infected Red Blood Cells in Deep Organs during Experimental Cerebral Malaria

Background: Infection with Plasmodium berghei ANKA (PbA) in susceptible mice induces a syndrome called experimental cerebral malaria (ECM) with severe pathologies occurring in various mouse organs. Immune mediators such as T cells or cytokines have been implicated in the pathogenesis of ECM. Red blood cells infected with PbA parasites have been shown to accumulate in the brain and other tissues during infection. This accumulation is thought to be involved in PbA–induced pathologies, which mechanisms are poorly understood. Methods and Findings: Using transgenic PbA parasites expressing the luciferase protein, we have assessed by real-time in vivo imaging the dynamic and temporal contribution of different immune factors in infected red blood cell (IRBC) accumulation and distribution in different organs during PbA infection. Using deficient mice or depleting antibodies, we observed that CD8 + T cells and IFN-c drive the rapid increase in total parasite biomass and accumulation of IRBC in the brain and in different organs 6–12 days post-infection, at a time when mice develop ECM. Other cells types like CD4 + T cells, monocytes or neutrophils or cytokines such as IL-12 and TNF-a did not influence the early increase of total parasite biomass and IRBC accumulation in different organs. Conclusions: CD8 + T cells and IFN-c are the major immune mediators controlling the time-dependent accumulation of P. berghei-infected red blood cells in tissues

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised