Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole

Contains fulltext : 137491.pdf (publisher's version ) (Open Access)Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n=11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from >/=6 laboratories, which included >/=95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 mug/ml for C. albicans, 0.5, 0.25, and 0.03 mug/ml for C. dubliniensis, 8, 1, and 0.25 mug/ml for C. glabrata, 8, 0.5, and 0.12 mug/ml for C. guilliermondii, 32, 0.5, and 0.25 mug/ml for C. krusei, 1, 0.06, and 0.06 mug/ml for C. lusitaniae, 1, 0.25, and 0.03 mug/ml for C. parapsilosis, and 1, 0.12, and 0.06 mug/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates

Gene-SGAN: discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering.

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and single nucleotide polymorphism data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-associated neuroimaging phenotypes

Cryptococcosis: a review of the brazilian experience for the disease Criptococose: revisão sobre a experiência brasileira sobre a doença

Cryptococcosis is a systemic mycosis caused by Cryptococcus neoformans. The disease occurs in patients with cellular immunodeficiency. The incidence of cryptococcosis arises with aids, and mycosis is one of the opportunistic infections that defines AIDS. After the HAART era the occurrence of cryptococcosis decreased all over the world, but it still continues to be a prevalent disease in Brazil. Thus, we consider this paper to be very important as a result of our reviewing of Brazilian literature regarding some relevant aspects of that disease.<br>Criptococose é micose sistêmica causada por Cryptococcus neoformans. A doença ocorre em pacientes com deficiência da imunidade celular. Com o aparecimento da doença AIDS, a incidência de criptococose aumentou, e a micose é uma das infecções oportunistas que definem um caso de AIDS. Após a era HAART, criptococose parece estar diminuindo no mundo todo, mas continua sendo uma doença prevalente no Brasil. Este artigo visa a análise da contribuição dos autores brasileiros sobre vários aspectos da doença