Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients.

BACKGROUND Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair

DNA duplexes containing unnatural base-pair surrogates are attractive biomolecular nanomaterials with potentially beneficial photophysical or electronic properties. Herein we report the first X-ray structure of a duplex containing a phen-pair in the center of the double helix in a zipper like stacking arrangement.

The Complexity of Non-Iterated Probabilistic Justification Logic

The logic PJ is a probabilistic logic defined by adding (noniterated) probability operators to the basic justification logic J. In this paper we establish upper and lower bounds for the complexity of the derivability problem in the logic PJ. The main result of the paper is that the complexity of the derivability problem in PJ remains the same as the complexity of the derivability problem in the underlying logic J, which is π[p/2] -complete. This implies that the probability operators do not increase the complexity of the logic, although they arguably enrich the expressiveness of the language.

From protein microarray to biology: The discovery of epigenetic regulatory molecules

Chromatin, composed of repeating nucleosome units, is the genetic polymer of life. To aid in DNA compaction and organized storage, the double helix wraps around a core complex of histone proteins to form the nucleosome, and is therefore no longer freely accessible to cellular proteins for the processes of transcription, replication and DNA repair. Over the course of evolution, DNA-based applications have developed routes to access DNA bound up in chromatin, and further, have actually utilized the chromatin structure to create another level of complexity and information storage. The histone molecules that DNA surrounds have free-floating tails that extend out of the nucleosome. These tails are post-translationally modified to create docking sites for the proteins involved in transcription, replication and repair, thus providing one prominent way that specific genomic sequences are accessed and manipulated. Adding another degree of information storage, histone tail-modifications paint the genome in precise manners to influence a state of transcriptional activity or repression, to generate euchromatin, containing gene-dense regions, or heterochromatin, containing repeat sequences and low-density gene regions. The work presented here is the study of histone tail modifications, how they are written and how they are read, divided into two projects. Both begin with protein microarray experiments where we discover the protein domains that can bind modified histone tails, and how multiple tail modifications can influence this binding. Project one then looks deeper into the enzymes that lay down the tail modifications. Specifically, we studied histone-tail arginine methylation by PRMT6. We found that methylation of a specific histone residue by PRMT6, arginine 2 of H3, can antagonize the binding of protein domains to the H3 tail and therefore affect transcription of genes regulated by the H3-tail binding proteins. Project two focuses on a protein we identified to bind modified histone tails, PHF20, and was an endeavor to discover the biological role of this protein. Thus, in total, we are looking at a complete process: (1) histone tail modification by an enzyme (here, PRMT6), (2) how this and other modifications are bound by conserved protein domains, and (3) by using PHF20 as an example, the functional outcome of binding through investigating the biological role of a chromatin reader. ^

Energy, Complexity and Strategies of Evolution. En: Avá, nº 14

Cultural evolution has long been among the themes of anthropology but it has never ranked high. It is left mainly to archaeologists because they have to make sense of how society works and survives through time–a concern that has pretty much been abandoned by many cultural anthropologists. Anthropologists today seem little motivated to find out how society works, but rather to make the world a better place to live in for a particular population. The challenges of atmospheric change, nuclear proliferation, environmental degradation and resource exhaustion, the emergence of life threatening species–these challenges of contemporary evolution have awakened less interest in anthropology. The concern with cultural evolution seems to be of greater interest to non-anthropologists, such as in the work of Jarrod Diamond (2005), a biologist, and the genre that as emerged as Big History, with the works of David Christian (2005) and others. Among the few contemporary anthropologists who have sought the dynamics of cultural evolution, the work of Joseph Tainter (1996) stands out.

Interstitial water chemistry of ODP Leg 103 sites

Interstitial waters were squeezed from strata recovered at Sites 637-641 of ODP Leg 103 on the Galicia margin, along the northwestern Iberian continental margin in the northeast Atlantic. Chemical profiles of Site 638 show the most complexity, which appears to be related to an unconformity in the strata between Cretaceous and Neogene sediments and to rapid deposition of Cretaceous syn-rift sediments upon pre-rift strata. Analyses of waters from all of the Leg 103 sites show generally antithetical trends for calcium and magnesium; calcium increases with depth as magnesium decreases. No calcium-magnesium 'crossover' profiles are observed in these data. Data from Site 637 show an unusual pattern; calcium increases with increasing depth, but magnesium remains relatively constant. Sulfate is either stable or shows an overall decrease with depth, and boron profiles show some structure. At all but one site (Site 638), strontium profiles do not show marked depth structure. The structure of alkalinity and silica profiles is highly site dependent. Bromide profiles are, in general, constant. In nearly every case, observed bromide concentrations are near average seawater values. Relatively low concentrations of iron and manganese are common within the upper 10 m of the sediment sequence and typically are near detection limits at deeper depths

Planktic foraminifera from the Paleocene-Eocene Thermal Maximum at Shatsky Rise, Pacific Ocean

High-resolution biostratigraphic and quantitative studies of subtropical Pacific planktonic foraminiferal assemblages (Ocean Drilling Program, Leg 198 Shatsky Rise, Sites 1209 and 1210) are performed to analyse the faunal changes associated with the Paleocene-Eocene Thermal Maximum (PETM) at about 55.5 Ma. At Shatsky Rise, the onset of the PETM is marked by the abrupt onset of a negative carbon isotope excursion close to the contact between carbonate-rich ooze and overlying clay-rich ooze and corresponds to a level of poor foraminiferal preservation as a result of carbonate dissolution. Lithology, planktonic foraminiferal distribution and abundances, calcareous plankton and benthic events, and the negative carbon isotope excursion allow precise correlation of the two Shatsky Rise records. Results from quantitative analyses show that Morozovella dominates the assemblages and that its maximum relative abundance is coincident with the lowest delta 13C values, whereas subbotinids are absent in the interval of maximum abundance of Morozovella. The excursion taxa (Acarinina africana, Acarinina sibaiyaensis, and Morozovella allisonensis) first appear at the base of the event. Comparison between the absolute abundances of whole specimens and fragments of genera demonstrate that the increase in absolute abundance of Morozovella and the decrease of Subbotina are not an artifact of selective dissolution. Moreover, the shell fragmentation data reveal Subbotina to be the more dissolution-susceptible taxon. The upward decrease in abundance of Morozovella species and the concomitant increase in test size of Morozovella velascoensis are not controlled by dissolution. These changes could be attributed to the species' response to low nutrient supply in the surface waters and to concomitant changes in the physical and chemical properties of the seawater, including increased surface stratification and salinity. Comparison of the planktonic foraminiferal changes at Shatsky Rise to those from other PETM records (Sites 865 and 690) highlights significant similarities, such as the decline of Subbotina at the onset of the event, and discrepancies, including the difference in abundance of the excursion taxa. The observed planktonic foraminifera species response suggests a warm-oligotrophic scenario with a high degree of complexity in the ocean structure.

Environmental policy and knowledge. Copying with complexity through inclusive management

Scholars agree that governance of the public environment entails cooperation between science, policy and society. This requires the active role of public managers as catalysts of knowledge co-production, addressing participatory arenas in relation to knowledge integration and social learning. This paper deals with the question of whether public managers acknowledge and take on this task. A survey accessing Directors of Environmental Offices (EOs) of 64 municipalities was carried out in parallel for two regions - Tuscany (Italy) and Porto Alegre Metropolitan Region (Brazil). The survey data were analysed using the multiple correspondence method. Results showed that, regarding policy practices, EOs do not play the role of knowledge co-production catalysts, since when making environmental decisions they only use technical knowledge. We conclude that there is a gap between theory and practice, and identify some factors that may hinder local environmental managers in acting as catalyst of knowledge co-production, raising a further question for future research.