Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting

Purpose: In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events. Methods: Consecutive PCI patients treated with drug-eluting stenting (N = 870; 72.2% men; mean age = 62.6 ± 11.5) completed the EQ-5D post-PCI. The EQ-5D levels were dichotomized into 'no problems' (level 1) versus 'problems' (levels 2, 3); the visual analogue scale (VAS) was dichotomized using the 25th percentile (cut-off ≤60) indicating poor health status. Patients were followed up for 1-year clinical events (death or non-fatal myocardial infarction (MI)). Results: There were 53 deaths/MIs at follow-up. The EQ-5D health status dimensions mobility (HR:2.23; 95% CI:1.25-3.97), self-care (HR:3.09; 95% CI:1.54-6.20), and self-reported health status as measured with the EQ-VAS (HR:2.94; 95% CI:1.65-5.25) were independent predictors of death/MI and added to the predictive value of a model comprised of demographic and clinical characteristics. The EQ-5D dimensions usual activities, pain/discomfort, and anxiety/depression were not associated with adverse clinical events in adjusted analysis. Conclusions: Patient-rated health status predicted adverse clinical events at 1-year follow-up in PCI patients treated with drug-eluting stenting, with the risk being more than 2-fold indepe

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

A Systematic Screen to Discover and Analyze Apicoplast Proteins Identifies a Conserved and Essential Protein Import Factor

Parasites of the phylum Apicomplexa cause diseases that impact global health and economy. These unicellular eukaryotes possess a relict plastid, the apicoplast, which is an essential organelle and a validated drug target. However, much of its biology remains poorly understood, in particular its elaborate compartmentalization: four membranes defining four different spaces. Only a small number of organellar proteins have been identified in particular few proteins are known for non-luminal apicoplast compartments. We hypothesized that enlarging the catalogue of apicoplast proteins will contribute toward identifying new organellar functions and expand the realm of targets beyond a limited set of characterized pathways. We developed a bioinformatic screen based on mRNA abundance over the cell cycle and on phyletic distribution. We experimentally assessed 57 genes, and of 30 successful epitope tagged candidates eleven novel apicoplast proteins were identified. Of those, seven appear to target to the lumen of the organelle, and four localize to peripheral compartments. To address their function we then developed a robust system for the construction of conditional mutants via a promoter replacement strategy. We confirm the feasibility of this system by establishing conditional mutants for two selected genes – a luminal and a peripheral apicoplast protein. The latter is particularly intriguing as it encodes a hypothetical protein that is conserved in and unique to Apicomplexan parasites and other related organisms that maintain a red algal endosymbiont. Our studies suggest that this peripheral plastid protein, PPP1, is likely localized to the periplastid compartment. Conditional disruption of PPP1 demonstrated that it is essential for parasite survival. Phenotypic analysis of this mutant is consistent with a role of the PPP1 protein in apicoplast biogenesis, specifically in import of nuclear-encoded proteins into the organelle