Survival in Southern European patients waitlisted for kidney transplant after graft failure: A competing risk analysis

Background Whether patients waitlisted for a second transplant after failure of a previous kidney graft have higher mortality than transplant-näive waitlisted patients is uncertain. Methods We assessed the relationship between a failed transplant and mortality in 3851 adult KT candidates, listed between 1984–2012, using a competing risk analysis in the total population and in a propensity score-matched cohort. Mortality was also modeled by inverse probability weighting (IPTW) competing risk regression. Results At waitlist entry 225 (5.8%) patients had experienced transplant failure. All-cause mortality was higher in the post-graft failure group (16% vs. 11%; P = 0.033). Most deaths occurred within three years after listing. Cardiovascular disease was the leading cause of death (25.3%), followed by infections (19.3%). Multivariate competing risk regression showed that prior transplant failure was associated with a 1.5-fold increased risk of mortality (95% confidence interval [CI], 1.01–2.2). After propensity score matching (1:5), the competing risk regression model revealed a subhazard ratio (SHR) of 1.6 (95% CI, 1.01–2.5). A similar mortality risk was observed after the IPTW analysis (SHR, 1.7; 95% CI, 1.1–2.6). Conclusions Previous transplant failure is associated with increased mortality among KT candidates after relisting. This information is important in daily clinical practice when assessing relisted patients for a retransplant.This study was supported in part by the Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional±FEDER, RETICS (REDINREN RD16/0009/0006, RD16/0009/0031

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Ocean sprawl facilitates dispersal and connectivity of protected species

Highly connected networks generally improve resilience in complex systems. We present a novel application of this paradigm and investigated the potential for anthropogenic structures in the ocean to enhance connectivity of a protected species threatened by human pressures and climate change. Biophysical dispersal models of a protected coral species simulated potential connectivity between oil and gas installations across the North Sea but also metapopulation outcomes for naturally occurring corals downstream. Network analyses illustrated how just a single generation of virtual larvae released from these installations could create a highly connected anthropogenic system, with larvae becoming competent to settle over a range of natural deep-sea, shelf and fjord coral ecosystems including a marine protected area. These results provide the first study showing that a system of anthropogenic structures can have international conservation significance by creating ecologically connected networks and by acting as stepping stones for cross-border interconnection to natural populations

Search for triboson W±W±W∓ production in pp collisions at √s = 8 TeV with the ATLAS detector

This paper reports a search for triboson W±W±W∓ production in two decay channels (W±W±W∓ → ±ν±ν∓ν and W±W±W∓ → ±ν±ν j j with = e, μ) in proton-proton collision data corresponding to an integrated luminosity of 20.3 fb−1 at a centreof-mass energy of 8 TeV with the ATLAS detector at the Large Hadron Collider. Events with exactly three charged leptons, or two leptons with the same electric charge in association with two jets, are selected. The total number of events observed in data is consistent with the Standard Model (SM) predictions. The observed 95% confidence level upper limit on the SM W±W±W∓ production cross section is found to be 730 fb with an expected limit of 560 fb in the absence of SM W±W±W∓ production. Limits are also set on WWWW anomalous quartic gauge couplings

Temporal, spatial, and interspecific variation in geochemical signatures within fish otoliths, bivalve larval shells, and crustacean larvae

Geochemical signatures of early life stages are increasingly used to study population connectivity. This approach utilizes spatial variability in chemical signatures to predict natal or nursery origins of post-dispersal individuals by comparison with a chemical reference atlas created from individuals of known origin. To examine the relative importance of spatial, temporal, and species variation in elemental signatures, we synthesized the chemical information of otoliths, larval shells, and whole larvae from studies that employed natural geochemical signatures in San Diego County, USA between 1997 and 2009. We compared 8 elements analyzed from 4 bivalve species, 2 larval or juvenile fishes, and Stage 1 crab zoeae. Across all species, different sets of elements best discriminated among open-coast sites or within or among bays and lagoons. In mytilid mussels, which had the most complete record, all 8 elements were more variable over time than space at the site level, highlighting the need to resample the reference atlas during each study. More coarsely, however, bay and lagoon taxa maintained distinct chemical signatures both from each other and from those on the open coast, despite interannual variability. Spatially identifiable signatures for all species were likely imparted by a combination of pollution in bays and export to adjacent coastlines (copper, lead), a heterogeneous distribution of land-sourced elements (manganese, cobalt, uranium), and incorporation that may vary in response to temperature (barium, manganese, strontium) and salinity (7 elements). These results identify important elements for larval tracking of additional species depending on habitat and life history; however, source population signatures appear species-specific