There is an urgent need for new tools to improve our ability to diagnose tuberculosis (TB) and multidrugresistant TB (MDR-TB) in resource-poor settings. In a retrospective analysis undertaken in a region with a high incidence of TB, we evaluated the performance of the microscopic observation drug susceptibility assay (MODS), a novel assay developed in Perú which uses an inverted light microscope and culture in Middlebrook 7H9 broth to detect mycobacterial growth. MODS detected 94.0% of 1,908 positive sputum cultures, whereas Löwenstein-Jensen (LJ) culture detected only 86.9% (P < 0.001). The median time to culture positivity was 8 days (compared to 16 days for the same 208 samples by LJ culture; P < 0.001, Wilcoxon signed rank test). The results obtained by direct susceptibility testing using MODS demonstrated excellent concordance for isoniazid and rifampin and the detection of multidrug resistance with those obtained by indirect colorimetric methods: the microplate Alamar Blue assay (MABA) and the tetrazolium microplate assay (TEMA) (agreement, 95, 98, and 94%; kappa values, 0.8, 0.7, and 0.7, respectively). The concordance of the susceptibility testing results for ethambutol and streptomycin was poor. MODS is a novel assay which can detect the organisms responsible for TB and MDR-TB directly from sputum inexpensively, rapidly, and effectively. A comprehensive prospective evaluation of MODS is under way in Perú, and independent validation in nonresearch laboratories should be undertaken at the earliest opportunity.Every single day at least 6,000 people die of tuberculosis (TB), a curable respiratory disease. The diagnosis of TB by sputum smear microscopy is an integral feature of the World Health Organization DOTS (direct observation of treatmentshort-course chemotherapy) strategy for global TB control (25). Low cost, simplicity, and inherent detection of the most infectious cases are the three principal advantages of microscopy for acid-fast bacilli. However, the sensitivity of microscopy for the detection of all cases is low, even when the optimum sensitivity of microscopy is achieved (approximately half of all culture-positive cases are smear negative), and the performance of microscopy is highly variable. Furthermore, the contribution of transmission of infection by smear-negative culture-positive patients (which, by definition, pass undetected when the sole mode of diagnosis is sputum smear) is not inconsiderable (2), and the potential impact of the detection and treatment of these patients is significant (19). Moreover, in this era of emerging drug resistance (9), the lack of information on drug susceptibility threatens the continuing role of the sputum smear as the sole tool for the diagnosis of the majority of cases of TB worldwide. The development of new, low-cost diagnostic tools offers the possibility of future TB control on the basis of culture-based diagnosis and more widespread, targeted susceptibility testing.The simple microscopic observation drug susceptibility assay (MODS) (5), developed in o...

ORCID IDs: 0000-0002-9014-9516 (D.V.); 0000-0001-8918-0711 (J.J.B.K.).Quantitative traits in plants are controlled by a large number of genes and their interaction with the environment. To disentangle the genetic architecture of such traits, natural variation within species can be explored by studying genotype-phenotype relationships. Genome-wide association studies that link phenotypes to thousands of single nucleotide polymorphism markers are nowadays common practice for such analyses. In many cases, however, the identified individual loci cannot fully explain the heritability estimates, suggesting missing heritability. We analyzed 349 Arabidopsis accessions and found extensive variation and high heritabilities for different morphological traits. The number of significant genome-wide associations was, however, very low. The application of genomic prediction models that take into account the effects of all individual loci may greatly enhance the elucidation of the genetic architecture of quantitative traits in plants. Here, genomic prediction models revealed different genetic architectures for the morphological traits. Integrating genomic prediction and association mapping enabled the assignment of many plausible candidate genes explaining the observed variation. These genes were analyzed for functional and sequence diversity, and good indications that natural allelic variation in many of these genes contributes to phenotypic variation were obtained. For ACS11, an ethylene biosynthesis gene, haplotype differences explaining variation in the ratio of petiole and leaf length could be identified.The natural phenomena of mutation and recombination that change the genetic code with each generation have given rise to the enormous genetic diversity between and within species. Through evolutionary processes, such as drift, migration, and selection, plants have accumulated a vast number of molecular polymorphisms that enabled adaptation to a wide range of environments (Kooke and Keurentjes, 2012). With the recent advancements in genetic and genomic tools, this nucleotide diversity can be fully surveyed to identify causal polymorphisms for many different plant phenotypes. This should allow the identification of molecular changes that provided evolutionary advantages and beneficial characteristics in agronomically important traits.Through selection on variation in performance, plants have adapted to different environments. Plant performance is directly determined by life history traits, such as flowering time and growth rate, which in turn depend on genetics, morphology, physiology, and the environment (Roff, 2007;Kooke et al., 2015). Understanding the regulation of plant growth and morphology is therefore essential for the comprehension of plant performance. Arabidopsis has adapted to a wide range of environments and displays an extensive variety in morphological and growth-related phenotypes. Its small genome size, the publicly available

Our data suggest that the homozygous CC genotype of the COX2.8473 T > C polymorphism may be associated with sarcoidosis susceptibility. No significant association with prognosis was detected.

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