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Data quality of the tokamaks diagnostics is often a neglected topic. In literature it is rather rare to find considerations regarding the data quality received from the diagnostic systems’ sensors. The scope of the paper is to provide a discussion regarding systems’ construction and analysis in scope of implementation of data quality monitoring methods for a new generation of diagnostics. Mainly considerations are performed regarding the necessity of DQM (Data Quality Monitoring) implementation, functionality, performance and required system resources. The covered topics are related to basics of system construction including: system layout and construction blocks, data processing stages, signal processing modes, system construction with resource estimation in scope of DQM implementation. Based on the covered points, it is possible to plan the extra resources or specific construction, to provide reliable design with data quality monitoring features. The data quality monitoring aspect is especially important in the modern diagnostics working with a real-time feedback loop. Such approach could be especially interesting for the ITER-like projects, since the quality of the data may directly influence the behavior of the control systems during plasma phenomena. The work is based on experience in design work of various high performance diagnostic systems for plasma physics and high energy physics.

The prediction accuracies of genomic selection depend on several factors, including the genetic architecture of target traits, the number of traits considered at a given time, and the statistical models. Here, we assessed the potential of single-trait (ST) and multi-trait (MT) genomic prediction models for durum wheat on yield and quality traits using a breeding panel (BP) of 170 varieties and advanced breeding lines, and a doubled-haploid (DH) population of 154 lines. The two populations were genotyped with the Infinium iSelect 90K SNP assay and phenotyped for various traits. Six ST-GS models (RRBLUP, G-BLUP, BayesA, BayesB, Bayesian LASSO, and RKHS) and three MT prediction approaches (MTBayesA, MT-Matrix, and MT-SI approaches which use economic selection index as a trait value) were applied for predicting yield, protein content, gluten index, and alveograph measures. The ST prediction accuracies ranged from 0.5 to 0.8 for the various traits and models and revealed comparable prediction accuracies for most of the traits in both populations, except BayesA and BayesB, which better predicted gluten index, tenacity, and strength in the DH population. The MT-GS models were more accurate than the ST-GS models only for grain yield in the BP. Using BP as a training set to predict the DH population resulted in poor predictions. Overall, all the six ST-GS models appear to be applicable for GS of yield and gluten strength traits in durum wheat, but we recommend the simple computational models RR-BLUP or GBLUP for predicating single trait and MT-SI for predicting yield and protein simultaneously.

Growing resistant wheat (Triticum aestivum L) varieties is an important strategy for the control of leaf rust, caused by Puccinia triticina Eriks. This study sought to identify the chromosomal location and effects of leaf rust resistance loci in five Canadian spring wheat cultivars. The parents and doubled haploid lines of crosses Carberry/AC Cadillac, Carberry/Vesper, Vesper/Lillian, Vesper/Stettler and Stettler/Red Fife were assessed for leaf rust severity and infection response in field nurseries in Canada near Swift Current, SK from 2013 to 2015, Morden, MB from 2015 to 2017 and Brandon, MB in 2016, and in New Zealand near Lincoln in 2014. The populations were genotyped with the 90K Infinium iSelect assay and quantitative trait loci (QTL) analysis was performed. A high density consensus map generated based on 14 doubled haploid populations and integrating SNP and SSR markers was used to compare QTL identified in different populations. AC Cadillac contributed QTL on chromosomes 2A, 3B and 7B (2 loci), Carberry on 1A, 2B (2 loci), 2D, 4B (2 loci), 5A, 6A, 7A and 7D, Lillian on 4A and 7D, Stettler on 2D and 6B, Vesper on 1B, 1D, 2A, 6B and 7B (2 loci), and Red Fife on 7A and 7B. Lillian contributed to a novel locus QLr.spa-4A, and similarly Carberry at QLr.spa-5A. The discovery of novel leaf rust resistance QTL QLr.spa-4A and QLr.spa-5A, and several others in contemporary Canada Western Red Spring wheat varieties is a tremendous addition to our present knowledge of resistance gene deployment in breeding. Carberry demonstrated substantial stacking of genes which could be supplemented with the genes identified in other cultivars with the expectation of increasing efficacy of resistance to leaf rust and longevity with little risk of linkage drag.

Some durum wheat (Triticum turgidum L. var durum) cultivars have the genetic propensity to accumulate cadmium (Cd) in the grain. A major gene controlling grain Cd concentration designated as Cdu1 has been reported on 5B, but the genetic factor(s) conferring the low Cd phenotype are currently unknown. The objectives of this study were to saturate the chromosomal region harboring Cdu1 with newly developed PCR-based markers and to investigate the colinearity of this wheat chromosomal region with rice (Oryza sativa L.) and Brachypodium distachyon genomes. Genetic mapping of markers linked to Cdu1 in a population of recombinant inbred substitution lines revealed that the gene(s) associated with variation in Cd concentration resides in wheat bin 5BL9 between fraction breakpoints 0.76 and 0.79. Genetic mapping and quantitative trait locus (QTL) analysis of grain Cd concentration was performed in 155 doubled haploid lines from the cross W9262-260D3 (low Cd) by Kofa (high Cd) revealed two expressed sequence tag markers (ESMs) and one sequence tagged site (STS) marker that co-segregated with Cdu1 and explained >80% of the phenotypic variation in grain Cd concentration. A second, minor QTL for grain Cd concentration was also identified on 5B, 67 cM proximal to Cdu1. The Cdu1 interval spans 286 kbp of rice chromosome 3 and 282 kbp of Brachypodium chromosome 1. The markers and rice and Brachypodium colinearity described here represent tools that will assist in the positional cloning of Cdu1 and can be used to select for low Cd accumulation in durum wheat breeding programs targeting this trait. The isolation of Cdu1 will further our knowledge of Cd accumulation in cereals as well as metal accumulation in general.

This randomized, open-label trial compared two regimens for the initial treatment of human immunodeficiency virus (HIV) infection: tenofovir disoproxil fumarate and emtricitabine plus efavirenz or a fixed dose of zidovudine and lamivudine plus efavirenz. Through week 48, the first regimen was superior in terms of viral suppression, CD4-cell response, and adverse events leading to discontinuation of the medication. As this trial continues, it will be important to assess any differences in long-term toxic effects, especially with regard to lipoatrophy and hyperlipidemia. For the initial treatment of HIV, a regimen of tenofovir and emtricitabine plus efavirenz was superior in terms of viral suppression, CD4-cell response, and adverse events through week 48. Highly active antiretroviral therapy has fundamentally altered the course of human immunodeficiency virus (HIV) infection by making it possible to suppress the plasma viral load below the limit of detection and to increase the number of CD4 cells. 1 The cornerstone of durable suppression of HIV replication is maintenance of a potent and tolerable regimen to which the patient can adhere. Adherence is necessary to prevent the emergence and replication of drug-resistant strains of the virus. 2 Current guidelines for the management of HIV infection recommend the use of zidovudine or tenofovir disoproxil fumarate (DF) with lamivudine or emtricitabine as preferred nucleoside . . .

Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye’s incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye–wheat introgressions.

Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir—a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions—coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide. In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were screened and enrolled at 126 outpatient centres in 10 countries in Australia, Europe, Latin America, and North America. Participants were previously untreated adults (HIV-1 RNA ≥500 copies per mL) with estimated glomerular filtration rate of at least 30 mL/min. Chronic hepatitis B virus or hepatitis C co-infection was allowed. We randomly assigned participants (1:1) to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo, once a day for 144 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of −12%. This study is registered with ClinicalTrials.gov, number NCT02607956. Between Nov 11, 2015, and July 15, 2016, 742 participants were screened for eligibility, of whom 657 were randomly assigned to treatment (327 with bictegravir, emtricitabine, and tenofovir alafenamide fixed-dose combination [bictegravir group] and 330 with dolutegravir plus emtricitabine and tenofovir alafenamide [dolutegravir group]). 320 participants who received the bictegravir regimen and 325 participants who received the dolutegravir regimen were included in the primary efficacy analyses. At week 48, HIV-1 RNA <50 copies per mL was achieved in 286 (89%) of 320 participants in the bictegravir group and 302 (93%) of 325 in the dolutegravir group (difference −3·5%, 95·002% CI −7·9 to 1·0, p=0·12), showing non-inferiority of the bictegravir regimen to the dolutegravir regimen. No treatment-emergent resistance to any study drug was observed. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 [2%] of 320 in the bictegravir group and 1 [<1%] 325 in the dolutegravir group). Study drug-related adverse events were less common in the bictegravir group than in the dolutegravir group (57 [18%] of 320 vs 83 [26%] of 325, p=0·022). At 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen. Gilead Sciences Inc.

Recent trends in the HIV response are especially concerning. Although the number of new HIV infections and AIDS-related deaths have markedly decreased since the epidemic peaked, little progress has been made in reducing new infections in the past decade. Without further reductions in HIV incidence, a resurgence of the epidemic is inevitable, as the largest ever generation of young people age into adolescence and adulthood. Yet where vigilance and renewed efforts are needed, there are disturbing indications that the world's commitment is waning. Allowing the HIV epidemic to rebound would be catastrophic for the communities most affected by HIV and for the broader field of global health. If the world cannot follow through on HIV, which prompted such an extraordinary global mobilisation, hopes for achieving the ambitious health aims outlined in the SDGs will inevitably dim.At this moment of uncertainty for the future of the HIV response and for global health generally, the International AIDS Society and The Lancet convened an international Commission of global experts and stakeholders to assess the future of the HIV response in the context of a more integrated approach to health. A central finding of the Commission is that the HIV epidemic is not on track to end and that existing tools are insufficient. Although antiretroviral therapy (ART) has transformed the HIV response by averting deaths, improving quality of life, and preventing new HIV infections, HIV treatment alone will not end the epidemic. The UNAIDS 90-90-90 approach must be accompanied by a similarly robust commitment to scaled-up primary HIV prevention and to the development of a preventive vaccine and a functional cure for HIV. Ironically, the diminishing energy on HIV is occurring at the moment when lessons learned during the HIV response could serve as pathfinders in the quest for sustainable health for all.

Wheat was one of the crops domesticated in the Fertile Crescent region approximately 10,000 years ago. Despite undergoing recent polyploidization, hull-to-free-thresh transition events, and domestication bottlenecks, wheat is now grown in over 130 countries and accounts for a quarter of the world’s cereal production. The main reason for its widespread success is its broad genetic diversity that allows it to thrive in different environments. To trace historical selection and hybridization signatures, genome scans were performed on two datasets: approximately 113K SNPs from 921 predominantly bread wheat accessions and approximately 110K SNPs from about 400 wheat accessions representing all ploidy levels. To identify environmental factors associated with the loci, a genome–environment association (GEA) was also performed. The genome scans on both datasets identified a highly differentiated region on chromosome 4A where accessions in the first dataset were dichotomized into a group (n = 691), comprising nearly all cultivars, wild emmer, and most landraces, and a second group (n = 230), dominated by landraces and spelt accessions. The grouping of cultivars is likely linked to their potential ancestor, bread wheat cv. Norin-10. The 4A region harbored important genes involved in adaptations to environmental conditions. The GEA detected loci associated with latitude and temperature. The genetic signatures detected in this study provide insight into the historical selection and hybridization events in the wheat genome that shaped its current genetic structure and facilitated its success in a wide spectrum of environmental conditions. The genome scans and GEA approaches applied in this study can help in screening the germplasm housed in gene banks for breeding, and for conservation purposes.

Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. The 2007 criteria for HIV-associated neurocognitive disorders (HAND), sometimes called the Frascati criteria, can falsely classify over 20% of cognitively healthy individuals as having cognitive impairment. Minimum criteria for HAND are met on the basis of performance on cognitive tests alone, which might not be appropriate for populations with diverse educational and socioeconomic backgrounds. Imprecise phenotyping of cognitive impairment can limit mechanistic research, biomarker discovery and treatment trials. Importantly, overestimation of cognitive impairment carries the risk of creating fear among people living with HIV and worsening stigma and discrimination towards these individuals. To address this issue, we established the International HIV-Cognition Working Group, which is globally representative and involves the community of people living with HIV. We reached consensus on six recommendations towards a new approach for diagnosis and classification of cognitive impairment in people living with HIV, intended to focus discussion and debate going forward. We propose the conceptual separation of HIV-associated brain injury — including active or pretreatment legacy damage — from other causes of brain injury occurring in people living with HIV. We suggest moving away from a quantitative neuropsychological approach towards an emphasis on clinical context. Our recommendations are intended to better represent the changing profile of cognitive impairment in people living with HIV in diverse global settings and to provide a clearer framework of classification for clinical management and research studies.Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. In this Consensus Statement, the International HIV-Cognition Working Group have outlined six recommendations towards a new approach, intended to better represent changes in the spectrum of HIV disease in the modern era of antiretroviral therapy.