Factors affecting recurrence risk in her2 positive dcis

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High-density molecular characterization and association mapping in Ethiopian durum wheat landraces reveals high diversity and potential for wheat breeding

Durum wheat (Triticum turgidum subsp. durum) is a key crop worldwide, and yet, its improvement and adaptation to emerging environmental threats is made difficult by the limited amount of allelic variation included in its elite pool. New allelic diversity may provide novel loci to international crop breeding through quantitative trait loci (QTL) mapping in unexplored material. Here, we report the extensive molecular and phenotypic characterization of hundreds of Ethiopian durum wheat landraces and several Ethiopian improved lines. We test 81 587 markers scoring 30 155 single nucleotide polymorphisms and use them to survey the diversity, structure, and genome-specific variation in the panel. We show the uniqueness of Ethiopian germplasm using a siding collection of Mediterranean durum wheat accessions. We phenotype the Ethiopian panel for ten agronomic traits in two highly diversified Ethiopian environments for two consecutive years and use this information to conduct a genome-wide association study. We identify several loci underpinning agronomic traits of interest, both confirming loci already reported and describing new promising genomic regions. These loci may be efficiently targeted with molecular markers already available to conduct marker-assisted selection in Ethiopian and international wheat. We show that Ethiopian durum wheat represents an important and mostly unexplored source of durum wheat diversity. The panel analysed in this study allows the accumulation of QTL mapping experiments, providing the initial step for a quantitative, methodical exploitation of untapped diversity in producing a better wheat

Genome wide association study to identify the genetic base of smallholder farmer preferences of Durum wheat traits

Smallholder agriculture involves millions of farmers worldwide. A methodical utilization of their traditional knowledge in modern breeding efforts may help the production of locally adapted varieties better addressing their needs. In this study, a combination of participatory approaches, genomics, and quantitative genetics is used to trace the genetic basis of smallholder farmer preferences of durum wheat traits. Two smallholder communities evaluated 400 Ethiopian wheat varieties, mostly landraces, for traits of local interest in two locations in the Ethiopian highlands. For each wheat variety, farmers provided quantitative evaluations of their preference for flowering time, spike morphology, tillering capacity, and overall quality. Ten agronomic and phenology traits were simultaneously measured on the same varieties, providing the means to compare them with farmer traits. The analysis of farmer traits showed that they were partially influenced by gender and location but were repeatable and heritable, in some cases more than metric traits. The durum wheat varieties were genotyped for more than 80,000 SNP markers, and the resulting data was used in a genome wide association (GWA) study providing the molecular dissection of smallholder farmers' choice criteria

Post-progression evaluation of patients treated with nivolumab for advanced non-small cell lung cancer: A prospective cohort analysis

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Pre-transplant psoas muscle density as a ready-to-use and low-cost predictor of patient survival after liver transplant

Background: Sarcopenia, defined as low muscle mass with reduced function, is frequently encountered in cirrhotic patients and is a major predictor of adverse events, including post-liver transplant (LT) outcome. Objectives: This study assessed the impact of sarcopenia using computed tomography (CT-based measurements on post-LT mortality and complications. Methods: From January 2008 to June 2016, 646 adult patients underwent 613 LTs at our institution. We analyzed the postoperative outcome of 287 patients who had pathologically proven cirrhosis on the explanted liver and who had performed a CT examination three months before LT. Psoas muscle density (PMD) was detected for every patient using standard instruments present in the radiological workstation and was related to postoperative survival rates and complications. Statistical analysis was carried out using the appropriate tests. Results: Postoperative mortality was 6.3%. At least one grade III-IV postoperative complication was experienced by 121 patients. Respiratory and infective complications occurred in 30 and 32 patients, respectively. Also, PMD was an independent predictor of postoperative mortality (P = 0.021), respiratory complications (P = 0.015), and infections (P = 0.010). The ROC analysis identified a PMD 43.72 HU as the best cutoff value for predicting 90-day mortality after LT. Conclusions: Psoas muscle density accurately predicted post-LT mortality and complications. Its ease and low-cost determination can allow widespread use of this parameter to improve clinical care and help with the decision to give these patients some priority on the transplant waiting list

Portal Vein Embolization is Associated with Reduced Liver Failure and Mortality in High-Risk Resections for Perihilar Cholangiocarcinoma

Background Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. Objective This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. Methods Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. Results A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p < 0.001 and p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p < 0.001), as was biliary leakage (10% vs. 35%, p < 0.01), intra-abdominal abscesses (19% vs. 34%, p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). Conclusion PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC

Heterosis Is Prevalent for Multiple Traits in Diverse Maize Germplasm

BACKGROUND: Heterosis describes the superior phenotypes observed in hybrids relative to their inbred parents. Maize is a model system for studying heterosis due to the high levels of yield heterosis and commercial use of hybrids. METHODS: The inbred lines from an association mapping panel were crossed to a common inbred line, B73, to generate nearly 300 hybrid genotypes. Heterosis was evaluated for seventeen phenotypic traits in multiple environments. The majority of hybrids exhibit better-parent heterosis in most of the hybrids measured. Correlations between the levels of heterosis for different traits were generally weak, suggesting that the genetic basis of heterosis is trait-dependent. CONCLUSIONS: The ability to predict heterosis levels using inbred phenotype or genetic distance between the parents varied for the different traits. For some traits it is possible to explain a significant proportion of the heterosis variation using linear modeling while other traits are more difficult to predict

Mixed model approaches for the identification of QTLs within a maize hybrid breeding program

Two outlines for mixed model based approaches to quantitative trait locus (QTL) mapping in existing maize hybrid selection programs are presented: a restricted maximum likelihood (REML) and a Bayesian Markov Chain Monte Carlo (MCMC) approach. The methods use the in-silico-mapping procedure developed by Parisseaux and Bernardo (2004) as a starting point. The original single-point approach is extended to a multi-point approach that facilitates interval mapping procedures. For computational and conceptual reasons, we partition the full set of relationships from founders to parents of hybrids into two types of relations by defining so-called intermediate founders. QTL effects are defined in terms of those intermediate founders. Marker based identity by descent relationships between intermediate founders define structuring matrices for the QTL effects that change along the genome. The dimension of the vector of QTL effects is reduced by the fact that there are fewer intermediate founders than parents. Furthermore, additional reduction in the number of QTL effects follows from the identification of founder groups by various algorithms. As a result, we obtain a powerful mixed model based statistical framework to identify QTLs in genetic backgrounds relevant to the elite germplasm of a commercial breeding program. The identification of such QTLs will provide the foundation for effective marker assisted and genome wide selection strategies. Analyses of an example data set show that QTLs are primarily identified in different heterotic groups and point to complementation of additive QTL effects as an important factor in hybrid performance

QTL Mapping of Combining Ability and Heterosis of Agronomic Traits in Rice Backcross Recombinant Inbred Lines and Hybrid Crosses

BACKGROUND: Combining ability effects are very effective genetic parameters in deciding the next phase of breeding programs. Although some breeding strategies on the basis of evaluating combining ability have been utilized extensively in hybrid breeding, little is known about the genetic basis of combining ability. Combining ability is a complex trait that is controlled by polygenes. With the advent and development of molecular markers, it is feasible to evaluate the genetic bases of combining ability and heterosis of elite rice hybrids through QTL analysis. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we first developed a QTL-mapping method for dissecting combining ability and heterosis of agronomic traits. With three testcross populations and a BCRIL population in rice, biometric and QTL analyses were conducted for ten agronomic traits. The significance of general combining ability and special combining ability for most of the traits indicated the importance of both additive and non-additive effects on expression levels. A large number of additive effect QTLs associated with performance per se of BCRIL and general combining ability, and dominant effect QTLs associated with special combining ability and heterosis were identified for the ten traits. CONCLUSIONS/SIGNIFICANCE: The combining ability of agronomic traits could be analyzed by the QTL mapping method. The characteristics revealed by the QTLs for combining ability of agronomic traits were similar with those by multitudinous QTLs for agronomic traits with performance per se of BCRIL. Several QTLs (1-6 in this study) were identified for each trait for combining ability. It demonstrated that some of the QTLs were pleiotropic or linked tightly with each other. The identification of QTLs responsible for combining ability and heterosis in the present study provides valuable information for dissecting genetic basis of combining ability