96 research outputs found

    Prediction Tools for Unfavourable Outcomes in Clostridium difficile Infection: A Systematic Review

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    CONTEXT: Identifying patients at risk for adverse outcomes of Clostridium difficile infection (CDI), including recurrence and death, will become increasingly important as novel therapies emerge, which are more effective than traditional approaches but very expensive. Clinical prediction rules (CPRs) can improve the accuracy of medical decision-making. Several CPRs have been developed for CDI, but none has gained a widespread acceptance. METHODS: We systematically reviewed studies describing the derivation or validation of CPRs for unfavourable outcomes of CDI, in medical databases (Medline, Embase, PubMed, Web of Science and Cochrane) and abstracts of conferences. RESULTS: Of 2945 titles and abstracts screened, 13 studies on the derivation of a CPR were identified: two on recurrences, five on complications (including mortality), five on mortality alone and one on response to treatment. Two studies on the validation of different severity indices were also retrieved. Most CPRs were developed as secondary analyses using cohorts assembled for other purposes. CPRs presented several methodological limitations that could explain their limited use in clinical practice. Except for leukocytosis, albumin and age, there was much heterogeneity in the variables used, and most studies were limited by small sample sizes. Eight models used a retrospective design. Only four studies reported the incidence of the outcome of interest, even if this is essential to evaluate the potential usefulness of a model in other populations. Only five studies performed multivariate analyses to adjust for confounders. CONCLUSIONS: The lack of weighing variables, of validation, calibration and measures of reproducibility, the weak validities and performances when assessed, and the absence of sensitivity analyses, all led to suboptimal quality and debatable utility of those CPRs. Evidence-based tools developed through appropriate prospective cohorts would be more valuable for clinicians than empirically-developed CPRs

    A low-cost, autonomous mobile platform for limnological investigations, supported by high-resolution mesoscale airborne imagery

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    Two complementary measurement systems – built upon an autonomous floating craft and a tethered balloon – for lake research and monitoring are presented. The autonomous vehicle was assembled on a catamaran for stability, and is capable of handling a variety of instrumentation for in situ and near-surface measurements. The catamaran hulls, each equipped with a small electric motor, support rigid decks for arranging equipment. An electric generator provides full autonomy for about 8 h. The modular power supply and instrumentation data management systems are housed in two boxes, which enable rapid setup. Due to legal restrictions in Switzerland (where the craft is routinely used), the platform must be observed from an accompanying boat while in operation. Nevertheless, the control system permits fully autonomous operation, with motion controlled by speed settings and waypoints, as well as obstacle detection. On-board instrumentation is connected to a central hub for data storage, with real-time monitoring of measurements from the accompanying boat. Measurements from the floating platform are complemented by mesoscale imaging from an instrument package attached to a He-filled balloon. The aerial package records thermal and RGB imagery, and transmits it in real-time to a ground station. The balloon can be tethered to the autonomous catamaran or to the accompanying boat. Missions can be modified according to imagery and/or catamaran measurements. Illustrative results showing the surface thermal variations of Lake Geneva demonstrate the versatility of the combined floating platform/balloon imagery system setup for limnological investigations

    Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.

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    Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence

    Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

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    The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymenas germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.</p

    Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review.

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    Cardiovascular Magnetic Resonance is increasingly used to differentiate the aetiology of cardiomyopathies. Late Gadolinium Enhancement (LGE) is the reference standard for non-invasive imaging of myocardial scar and focal fibrosis and is valuable in the differential diagnosis of ischaemic versus non-ischaemic cardiomyopathy. Diffuse fibrosis may go undetected on LGE imaging. Tissue characterisation with parametric mapping methods has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by LGE. Native and post-contrast T1 mapping in particular has shown promise as a novel biomarker to support diagnostic, therapeutic and prognostic decision making in ischaemic and non-ischaemic cardiomyopathies as well as in patients with acute chest pain syndromes. Furthermore, changes in the myocardium over time may be assessed longitudinally with this non-invasive tissue characterisation method

    Assessment of different methods of rice (Oryza sativa. L) cultivation affecting growth parameters, soil chemical, biological, and microbiological properties, water saving, and grain yield in rice–rice system

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    Field experiments were conducted at DRR farm located at ICRISAT, Patancheru, in sandy clay loam soils during four seasons, Kharif 2008, Rabi 2008–2009, Kharif 2009 and Rabi 2009–2010, to investigate growth parameters, water-saving potential, root characteristics, chemical, biological, and microbial properties of rhizosphere soil, and grain yield of rice (Oryza sativa L.) by comparing the plants grown with system of rice intensification (SRI) methods, with organic or organic + inorganic fertilization, against current recommended best management practices (BMP). All the growth parameters including plant height, effective tillers (10–45 %), panicle length, dry matter, root dry weight (24–57 %), and root volume (10–66 %) were found to be significantly higher with in SRI-organic + inorganic over BMP. With SRI-organic fertilization, growth parameters showed inconsistent results; however, root dry weight (3–77 %) and root volume (31–162 %) were found significantly superior compared to BMP. Grain yield was found significantly higher in SRI-organic + inorganic (12–23 and 4–35 % in the Kharif and Rabi seasons, respectively), while with SRI-organic management, yield was found higher (4–34 %) only in the Rabi seasons compared to BMP. An average of 31 and 37 % of irrigation water were saved during Kharif and Rabi seasons, respectively, with both SRI methods of rice cultivation compared to BMP. Further, total nitrogen, organic carbon%, soil dehydrogenase, microbial biomass carbon, total bacteria, fungi, and actinomycetes were found higher in the two SRI plots in comparison to BMP. It is concluded that SRI practices create favorable conditions for beneficial soil microbes to prosper, save irrigation water, and increase grain yield

    The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia

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    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in Blastomyces.Author SummaryDimorphic fungal pathogens including Blastomyces are the cause of major fungal diseases in North and South America. The genus Emmonsia includes species infecting small mammals as well as a newly emerging pathogenic species recently reported in HIV-positive patients in South Africa. Here, we synthesize both genome sequencing of four isolates of Blastomyces and two species of Emmonsia as well as deep sequencing of Blastomyces RNA to draw major new insights into the evolution of this group and the pathogen response to infection. We investigate the trajectory of genome evolution of this group, characterizing the phylogenetic relationships of these species, a remarkable genome expansion that formed large isochore-like regions of low GC content in Blastomyces, and variation of gene content, related to host interaction, among the dimorphic fungal pathogens. Using RNA-Seq, we profile the response of Blastomyces to macrophage and mouse pulmonary infection, identifying key pathways and novel virulence factors. The identification of key fungal genes involved in adaptation to the host suggests targets for further study and therapeutic intervention in Blastomyces and related dimorphic fungal pathogens
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