19 research outputs found
Analysis of recurrent events with an associated informative dropout time: Application of the joint frailty model.
This paper considers the analysis of a repeat event outcome in clinical trials of chronic diseases in the context of dependent censoring (e.g. mortality). It has particular application in the context of recurrent heart failure hospitalisations in trials of heart failure. Semi-parametric joint frailty models (JFMs) simultaneously analyse recurrent heart failure hospitalisations and time to cardiovascular death, estimating distinct hazard ratios whilst individual-specific latent variables induce associations between the two processes. A simulation study was carried out to assess the suitability of the JFM versus marginal analyses of recurrent events and cardiovascular death using standard methods. Hazard ratios were consistently overestimated when marginal models were used, whilst the JFM produced good, well-estimated results. An application to the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity programme was considered. The JFM gave unbiased estimates of treatment effects in the presence of dependent censoring. We advocate the use of the JFM for future trials that consider recurrent events as the primary outcome. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd
Yersinia pseudotuberculosis serotype O : 1 infection in a captive Seba's short tailed-fruit bat (Carollia perspicillata) colony in Switzerland
BackgroundBetween February and April 2016, a slight increase in mortality was observed in a colony consisting of 400 captive Seba's short-tailed bats (Carollia perspicillata). These animals cohabited with other nocturnal animal species in a dome of a private zoo in Switzerland.ResultsGross and histological analysis of two (14.3%) out of the 13 animals submitted for necropsy within this period revealed a necrosuppurative pneumonia, hepatitis, splenitis, enterocolitis, and endometritis, with abundant intralesional colonies of Gram-negative rods. Yersinia (Y.) pseudotuberculosis serotype O:1 and biotype 1 belonging to the sequence type ST90 was isolated from the affected organs in both animals. Following this diagnosis, 1/4 of the colony (99 animals) was culled and submitted for gross and histopathological analysis, and a bacterial culture selective for Yersinia spp. of lung, liver, and spleen was performed. From these 99 animals, one gravid female was tested and found to be positive for Y. pseudotuberculosis in the absence of clinical symptoms and histopathological lesions. PCR analysis of altogether three bacterial isolates for virulence factors revealed the presence of the ail gene, and one isolate was also positive for the virF and yadA plasmid genes.ConclusionsThese findings suggest that Carollia perspicillata are susceptible to lethal yersiniosis but do not represent a regular reservoir for Y. pseudotuberculosis. Culling of 1/4 of the population was sufficient to limit the spread of this infection among the colony. Moreover, no infections were detected in cohabitant nocturnal animals and caretakers, indicating that the zoonotic risk in this case was low.Peer reviewe
On the development of high temperature ammonia–water hybrid absorption–compression heat pumps
Occurrence and characterisation of Salmonella enterica subspecies diarizonae serovar 61: k: 1, 5, (7) in sheep in the federal state of Thuringia, Germany
Experimental results of an absorption-compression heat pump using the working fluid ammonia/water for heat recovery in industrial processes
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
A nearly complete system of average crystallographic ionic radii and its use for determining ionization potentials
De novo NAD+ synthesis enhances mitochondrial function and improves health
Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for several enzymes, including the sirtuin family of NAD+-dependent protein deacylases. Beneficial effects of increased NAD+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD+ synthesis pathway, controls cellular NAD+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver