Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Ambulatory management of heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) has significant adverse effects on the quality of life of many women, placing an economic burden on both health services and society at large. Thus, it is essential that all women with HMB have easy access to the proper diagnostic and therapeutic work-up in an outpatient fashion, avoiding the more time-consuming inpatient management. This new outpatient approach for HMB is one of the latest development of gynecological practice and can offer both diagnostic and therapeutic procedures. This manuscript aims to show the current possibilities of the modern management of HMB, which can be safely and effectively accomplished in the outpatient setting: global and directed endometrial biopsy, levonorgestrel intrauterine system insertion as well as minimally invasive surgical procedures (encompassing a variety of operative hysteroscopic procedures and second-generation endometrial ablation) are described below.

Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.

Spatio-temporal co-ordination of RhoA, Rac1 and Cdc42 activation during prototypical edge protrusion and retraction dynamics

The three canonical Rho GTPases RhoA, Rac1 and Cdc42 co-ordinate cytoskeletal dynamics. Recent studies indicate that all three Rho GTPases are activated at the leading edge of motile fibroblasts, where their activity fluctuates at subminute time and micrometer length scales. Here, we use a microfluidic chip to acutely manipulate fibroblast edge dynamics by applying pulses of platelet-derived growth factor (PDGF) or the Rho kinase inhibitor Y-27632 (which lowers contractility). This induces acute and robust membrane protrusion and retraction events, that exhibit stereotyped cytoskeletal dynamics, allowing us to fairly compare specific morphodynamic states across experiments. Using a novel Cdc42, as well as previously described, second generation RhoA and Rac1 biosensors, we observe distinct spatio-temporal signaling programs that involve all three Rho GTPases, during protrusion/retraction edge dynamics. Our results suggest that Rac1, Cdc42 and RhoA regulate different cytoskeletal and adhesion processes to fine tune the highly plastic edge protrusion/retraction dynamics that power cell motility.

Human Capital and Interethnic Marriage Decisions

Despite a longstanding belief that education importantly affects the process of immigrant assimilation, little is known about the relative importance of different mechanisms linking these two processes. This paper explores this issue through an examination of the effects of human capital on one dimension of assimilation, immigrant intermarriage. I argue that there are three primary mechanisms through which human capital affects the probability of intermarriage. First, human capital may make immigrants better able to adapt to the native culture thereby making it easier to share a household with a native. Second, it may raise the likelihood that immigrants leave ethnic enclaves, thereby decreasing the opportunity to meet potential spouses of the same ethnicity. Finally, assortative matching on education in the marriage market suggests that immigrants may be willing to trade similarities in ethnicity for similarities in education when evaluating potential spouses. Using a simple spouse-search model, I first derive an identification strategy for differentiating the cultural adaptability effect from the assortative matching effect, and then I obtain empirical estimates of their relative importance while controlling for the enclave effect. Using U.S. Census data, I find that assortative matching on education is the most important avenue through which human capital affects the probability of intermarriage. Further support for the model is provided by deriving and testing some of its additional implications.

THE NEW ROLE OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9: A CONNECTION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9, APOLIPOPROTEIN B, and AUTOPHAGY

Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of LDLR on the cell surface of hepatocytes. This PCSK9/LDLR complex enters the cell via endocytosis, where both PCSK9 and LDLR are removed via the lysosome pathway, resulting in decreased levels of LDLR and accumulation of LDL in the plasma. However, whether this is the exclusive function of PCSK9 on LDL metabolism was challenged by us; we observed PCSK9 interacted with apolipoprotein B (apoB) and increased apoB production, irrespective of the LDLR. ApoB is the primary structure protein of LDL particle and it also serves as the ligand for the LDL receptor. There is ample evidence showing that the levels of apoB are a better indicator for heart disease than either total cholesterol or LDL cholesterol levels. We used a second-generation adenoviral vector to overexpress PCSK9 (Ad-PCSK9) in wild-type C57BL/6 and LDLR deficient mice (Ldlr-/- and Ldlr-/-Apobec1-/-). Our study revealed that overexpression of PCSK9 promoted the production and secretion of apoB in the form of very-low density lipoprotein (VLDL), which is the precursor of LDL, in the 3 mouse models studied (C57BL/6J, Ldlr-/-, and Ldlr-/-Apobec1-/-). The increased apoB production in mice was regulated at post-transcriptional levels, since there was no difference in apoB mRNA levels between mice treated with Ad-PCSK9 and control vector Ad-Null. By using pulse-chase experiment on primary hepatocytes, we showed that overexpression of PCSK9 increased the secretion of apoB, independent of LDLR. In the circulation, we showed that PCSK9 was associated with LDL particles. By using 3 different protein–protein interaction assays of co-immunoprecipitation, mammalian two-hybrid system, and in situ proximity ligation assay, we demonstrated a direct protein–protein interaction between PCSK9 and apoB. The impact of this interaction inhibited the physiological removal process of apoB via autophagosome/lysosome pathway in an LDLR-independent fashion, resulting in increased production and secretion of apoB-containing lipoproteins. The significance of this process was shown in the Pcsk9 knockout mice in the background of Ldlr-/-Apobec1-/- mice (triple knockout mice); in the absence of Pcsk9 (triple knockout mice) the levels of cholesterol, triacylglycerol, and apoB decreased significantly in comparison to that of Ldlr-/-Apobec1-/- mice. Taken together, our study demonstrated a direct intracellular interaction of PCSK9 with apoB, resulting in the inhibition of apoB degradation via the autophagosome/lysosome pathway independent of LDLR. This discovery provides a new concept of the importance of PCSK9 and suggests new approaches for the therapeutic intervention of hyperlipidemia.

Avances metodológicos del proceso de adopción de los Planes de Ordenamiento de segunda generación frente a los vacios jurídicos de la Legislación Colombiana en materia de Ordenamiento Territorial a la luz del P.O.T. Armenia 2007/2019 “Una Ciudad para la Vida"

Las nuevas realidades territoriales, bajo el innovador panorama constitucional colombiano, requieren de procesos de planificación coherentes, ajustados a las necesidades reales de desarrollo de nuestras sociedades en constante crecimiento. Se requieren acciones inmediatas y contundentes de fortalecimiento, asistencia técnica, desarrollo institucional e implementación de instrumentos de Gestión y financiación del suelo, para responder a la insuficiente capacidad de los entes territoriales para asumir con responsabilidad la formulación e implementación de los instrumentos de planificación y ordenamiento territorial planteados por la ley y la normatividad urbanística vigente. Dicha normatividad, dada su falta de reglamentación y regulación, hace compleja su aplicación en pequeñas y medianas ciudades, debido a la deficiente capacidad operativa y ejecutoria que tienen sus administraciones. El 24 de enero de 1999 el Concejo Municipal de Armenia aprobaba el primer plan de ordenamiento territorial para un municipio Colombiano bajo el marco de la Ley de Desarrollo Territorial 388 de 1997. Veinticuatro horas después se produce un sismo de 6.4 grados (Richter) con epicentro a 24 kilómetros de distancia, generando devastadoras consecuencias en toda la región del eje cafetero, tanto en lo físico como en lo social: “Cuando teníamos las respuestas… cambiaron las preguntas". Las nuevas determinantes territoriales generadas como efecto de la tragedia pondrían el proceso de implementación del plan en un escenario complejo y contradictorio. A pesar de que el concepto de gestión del riesgo había sido abordado por el P.O.T., las realidades del desastre superaban la expectativa planificadora, desbordando cualquier escala de ejecutabilidad de la norma recientemente aprobada. El equipo de formulación del nuevo plan, bajo la coordinación del D.A.P.M. y con apoyo de la academia identificó de manera inmediata la complejidad del proceso. Además, realizó aportes que permitieran a los demás municipios Colombianos evitar cometer los mismos errores, superar los obstáculos, agilizar procesos particulares de planificación territorial y dotar así a sus municipios de unos Planes de Ordenamiento mas aterrizados, realizables y sobretodo mas consecuentes con las necesidades particulares de sus municipios.

El trabajo de derribar antinomias : los intentos de Helmut Plessner y Talcott Parsons

La relación entre comunidad y sociedad puede rastrearse de los orígenes de la sociología hasta la actualidad. Fue un punto central en el pensamiento de la segunda generación de padres fundadores -Durkheim, Tönnies, Weber-, lo fue luego en la sociología de Talcott Parsons, y es aún un fuerte centro de debate entre las diversas corrientes contemporáneas, tanto dentro de la sociología como en las ciencias políticas y la filosofía. En este sentido, la relación comunidad-sociedad continúa hasta el día de hoy suscitando polémicas e inspirando numerosos y sugerentes trabajos. No obstante, si bien en sus diferentes tratamientos presenta incontables diferencias, un elemento común es analizar la relación como dos polos excluyentes y antitéticos. Este trabajo se propone describir cómo dos pensadores provenientes de corrientes diferentes como Talcott Parsons y Helmut Plessner buscaron pensar ambos conceptos -comunidad y sociedad- no cómo elementos excluyentes, sino como dimensiones necesarias y presentes en todo nivel de la vida humana. Así, la intención es demostrar cómo dichos autores lograron integrar ambas dimensiones, a la vez que advertir sobre las consecuencias y dificultades de los intentos de superación o eliminación de esta relación.

Composition of minerals and rocks from the Markov Deep, Central Atlantic

The paper presents materials on composition and texture of weakly serpentinized ultrabasic rocks from the western and eastern walls of the Markov Deep (5°30.6'-5°32.4'N) in the rift valley of the Mid-Atlantic Ridge. Predominant harzburgites with protogranular and porphyroclastic textures contain two major generations of minerals: the first generation composes the bulk of rocks and consists of Ol_89.8-90.4 + En_90.2-90.8 + Di_91.8 + Chr (Cr#32.3-36.6, Mg#67.2-70.0), while the second generation composes very thin branching veinlets and consists of PlAn_32-47 + Ol_74.3-77.1 + Opx_55.7-71.9 + Cpx_67.5 + Amph_53.7-74.2 + Ilm. Syndeformational olivine neoblasts in recrystallization zones are highly magnesian. Concentrations and covariations of major elements in harzburgites indicate that these rocks are depleted in mantle residues (high Mg# of minerals and whole-rock samples and low in CaO, Al2O3, and TiO2) that are significantly enriched in trace HFSE and REE (Zr, Hf, Y, LREE, and all REE). Mineralogy and geochemistry of harzburgites were formed by interaction of mantle residues with hydrous, strongly fractionated melts that impregnated them. Mineral composition of veinlets in harzburgites and mineralogical-geochemical characteristics of related plagiogranites and gabbronorites suggest that these plagiogranites were produced by melt residuals after crystallization of gabbronorites. Modern characteristics of harzburgites were shaped by the following processes: (i) partial melting of mantle material simultaneously with its subsolidus deformations, (ii) brittle-plastic deformations associated with cataclastic flow and recrystallization, and (iii) melt percolation along zones of maximal stress relief and interaction of this melt with magnesian mantle residue.

Narrar la ausencia : Una lectura de Los topos de Félix Bruzzone y de Diario de una Princesa Montonera de Mariana Perez

En el presente trabajo abordamos los textos Los topos, de Félix Bruzzone y Diario de una Princesa Montonera, de Mariana Eva Perez para analizar en ellos los modos de recuperación del pasado reciente ligado con la última dictadura militar argentina desde la mirada de dos hijos de desaparecidos.

Petrology and geochemistry of volcanic rocks from ODP Sites 134-827, 134-829 and 134-830

Igneous rocks recovered from Ocean Drilling Program (ODP) Leg 134 Sites 827, 829, and 830 at the toe of the forearc slope of New Hebrides Island Arc were investigated, using petrography, mineral chemistry, major and trace element, and Sr, Nd, and Pb isotopic analyses. Basaltic and andesitic clasts, together with detrital crystals of plagioclase, pyroxenes, and amphiboles embedded in sed-lithic conglomerate or volcanic siltstone and sandstone of Pleistocene age, were recovered from Sites 827 and 830. Petrological features of these lava clasts suggest a provenance from the Western Belt of New Hebrides Island Arc; igneous constituents were incorporated into breccias and sandstones, which were in turn reworked into a second generation breccia. Drilling at Site 829 recovered a variety of igneous rocks including basalts and probably comagmatic dolerites and gabbros, plus rare ultramafic rocks. Geochemical features, including Pb isotopic ratios, of the mafic rocks are intermediate between midocean ridge basalts and island arc tholeiites, and these rocks are interpreted to be backarc basin basalts. No correlates of these mafic rocks are known from Espiritu Santo and Malakula islands, nor do they occur in the Pleistocene volcanic breccias at Sites 827 and 830. However, basalts with very similar trace element and isotopic compositions have been recovered from the northern flank of North d'Entrecasteaux Ridge at Site 828. It is proposed that igneous rocks drilled at Site 829 represent material from the North d'Entrecasteaux Ridge accreted onto the over-riding Pacific Plate during collision. An original depleted mantle harzburgitic composition is inferred for a serpentinite clast recovered at 407 meters below seafloor (mbsf) in Hole 829A. Its provenance is a matter of speculation. It could have been brought up along a deep thrust fault affecting the Pacific Plate at the colliding margin, or analogous to the Site 829 basaltic lavas, it may represent material accreted from the North d'Entrecasteaux Ridge.

Narrar la ausencia : Una lectura de Los topos de Félix Bruzzone y de Diario de una Princesa Montonera de Mariana Perez

En el presente trabajo abordamos los textos Los topos, de Félix Bruzzone y Diario de una Princesa Montonera, de Mariana Eva Perez para analizar en ellos los modos de recuperación del pasado reciente ligado con la última dictadura militar argentina desde la mirada de dos hijos de desaparecidos.

Narrar la ausencia : Una lectura de Los topos de Félix Bruzzone y de Diario de una Princesa Montonera de Mariana Perez

En el presente trabajo abordamos los textos Los topos, de Félix Bruzzone y Diario de una Princesa Montonera, de Mariana Eva Perez para analizar en ellos los modos de recuperación del pasado reciente ligado con la última dictadura militar argentina desde la mirada de dos hijos de desaparecidos.

Narrar la ausencia : Una lectura de Los topos de Félix Bruzzone y de Diario de una Princesa Montonera de Mariana Perez

En el presente trabajo abordamos los textos Los topos, de Félix Bruzzone y Diario de una Princesa Montonera, de Mariana Eva Perez para analizar en ellos los modos de recuperación del pasado reciente ligado con la última dictadura militar argentina desde la mirada de dos hijos de desaparecidos.