Binary systems and their nuclear explosions

Peer ReviewedPreprin

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

El concepto de devengo jur?dico introducido por el Decreto Legislativo 1425, el principio de asociaci?n, correlaci?n, equiparaci?n o matching, y la aplicaci?n de la NIIF 15

Due to the enactment of Legislative Decree Nro. 1425, this paper, points out the relevance of the concept of Juridical Accrual in our tax legal system; as well as the parameters that tax payers must take into account for its correct application in their day-to-day operations, which are understood as economic facts giving rise to taxable events subject to the Corporate Income Tax. On this basis, in order to provide the tools for its correct application of the aforesaid concept, we had incorporated into its analysis, required civil law aspects as they are mentioned by the own juridical definition of Accrual.A prop?sito de la publicaci?n del Decreto Legislativo 1425, el presente art?culo expone la relevancia, desde la perspectiva fiscal, del concepto de devengo jur?dico en nuestro ordenamiento jur?dico. Se describen, asimismo, los par?metros que deben considerar los contribuyentes, y que coadyuvar?n a sustentar su correcta aplicaci?n en las transacciones diarias, las cuales se entienden como hechos econ?micos susceptibles de generar hechos imponibles gravados con el impuesto a la renta corporativo. Es as? que, en virtud de lo indicado, y a efectos de brindar las herramientas necesarias para la correcta aplicaci?n del concepto jur?dico en menci?n, hemos incorporado al an?lisis de este los conceptos normativos propios de las instituciones jur?dicas sustentadas en nuestro ordenamiento jur?dico civil, cuya remisi?n ha sido efectuada, intr?nsecamente, por los alcances de la propia definici?n jur?dica del devengo

Extra-articular shoulder resections: Outcomes of 54 patients

BACKGROUND: The survival of patients with tumors around the shoulder treated with extra-articular resection, the rates of reconstructions-related complications, and the function of the shoulder cannot be estimated because of limited available data from mainly small published related series and case reports METHODS: We studied 54 patients with tumors around the shoulder treated with extra-articular shoulder resections and proximal humeral megaprosthetic reconstructions from 1985 to 2012. Mean tumor volume was 549\u2009cm3, and the mean length of the proximal humeral resection was 110\u2009mm. Mean follow-up was 7.8 years (range, 3-21 years). We evaluated the outcomes (survival, metastases, recurrences, and function) and the survival and complications of the reconstruction. RESULTS: Survival of patients with malignant tumors was 47%, 38%, and 35%, at 5, 10, and 20 years, respectively. Rates for metastasis and local recurrence were 60% and 18.5%, respectively. Survival was significantly higher for patients without metastases at diagnosis, tumor volume <549\u2009cm3, and type IV resections. Survival of reconstructions was 56% at 10 years and 48% 20 years. Overall, 19 patients (35.2%) experienced 30 complications (55.5%), the most common being soft tissue failures that required subsequent surgery without, however, implant removal. The mean Musculoskeletal Tumour Society score was 25 points, without any significant difference between the types of extra-articular resections. CONCLUSION: Tumor stage and volume as well as type of resection are important predictors of survival of patients with malignant tumors around the shoulder. Survival of the reconstructions is satisfactory; nevertheless, the complication rate is high. The Musculoskeletal Tumour Society score is similar with respect to the type of resection

Indocyanine green guidance improves the efficiency of extended pelvic lymph node dissection during laparoscopic radical prostatectomy

OBJECTIVES: To evaluate whether indocyanine green guidance can improve the quality of extended pelvic lymph node dissection in patients undergoing radical prostatectomy. METHODS: A total of 214 patients underwent laparoscopic radical prostatectomy with indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection. These patients (group A) were matched 1:1 for clinical risk groups according to the National Comprehensive Cancer Network classification with patients who underwent the same procedure without fluorescence guidance (group B). Biochemical recurrence was defined as two consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox regression models were used to identify predictors of biochemical recurrence. RESULTS: The median number of retrieved nodes was significantly higher in group A (22 vs 14, P < 0.001). The rate of lymph node metastases was higher in group A (65.9% vs 34.1%, P = 0.01). Increasing the yield of lymph node dissection was independently and negatively correlated with the biochemical recurrence risk in both overall and pN-positive patients (hazard ratio 0.97, P = 0.03; and hazard ratio 0.95, P = 0.02). The 5-year biochemical recurrence-free survival rates were (75.8% vs 65.9, P = 0.09) and (54.1% vs 24.9%, P = 0.023) for group A and group B in the overall cohort and pN-positive cohort, respectively. CONCLUSION: Indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection improves identification of lymphatic drainage, resulting in a higher number of lymph nodes and retrieved lymph node metastases, and allowing a more accurate local staging and a prolonged biochemical recurrence-free survival

A novel high-content analysis tool reveals Rab8-driven cytoskeletal reorganization through Rho GTPases, calpain and MT1-MMP

Rab8 is a small Ras-related GTPase that regulates polarized membrane transport to the plasma membrane. Here, we developed a high-content analysis (HCA) tool to dissect Rab8-mediated actin and focal adhesion reorganization that revealed that Rab8 activation significantly induced Rac1 and Tiam1 to mediate cortical actin polymerization and RhoA-dependent stress fibre disassembly. Rab8 activation increased Rac1 activity, whereas its depletion activated RhoA, which led to reorganization of the actin cytoskeleton. Rab8 was also associated with focal adhesions, promoting their disassembly in a microtubule-dependent manner. This Rab8 effect involved calpain, MT1-MMP (also known as MMP14) and Rho GTPases. Moreover, we demonstrate the role of Rab8 in the cell migration process. Indeed, Rab8 is required for EGF-induced cell polarization and chemotaxis, as well as for the directional persistency of intrinsic cell motility. These data reveal that Rab8 drives cell motility by mechanisms both dependent and independent of Rho GTPases, thereby regulating the establishment of cell polarity, turnover of focal adhesions and actin cytoskeleton rearrangements, thus determining the directionality of cell migration