Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial

BACKGROUND: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter. METHODS: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS. RESULTS: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively. CONCLUSIONS: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.ClinicalTrials.gov NCT02617589

Liquidity risk in spot foreign exchange markets

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN038509 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Evaluative Methodology of Interventions Concerning Bullying in School Environment (literature review).

info:eu-repo/semantics/nonPublishe

Common factors and causality in the dynamics of implied volatility surfaces:evidence from the FX OTC market

In this paper we explore the dynamics of Implied Volatility Surfaces (IVS) both in a single-currency framework, and in the context of a global, integrated market. We construct a parametric function of “moneyness” and “time-to-maturity” factors that correspond to common shapes of IVS with evident financial intuition. In the first part of the paper, we analyze the time series properties of the estimated factor loadings coefficients, and at the same time the intuition behind the derived associations between them. The second part of the paper, explores the interaction between IVSs of different currency pairs in two stages. In the first stage, shape transmission between IVSs is examined, using simple linear causality tests. We answer the question whether certain shapes in one currency are transmitted to another. The second stage, involves an exploratory factor analysis to uncover latent common factors, across all currencies, which explain part of IVS variability. Our results uncover large idiosyncratic components in the emerging markets IVSs and dominant common factors that explain most of the variability in the main European currencies

Itô’s Calculus and the Derivation of the Black–Scholes Option-Pricing Model

The purpose of this chapter is to develop certain relatively recent mathematical discoveries known generally as stochastic calculus (or more specifically as Itô’s Calculus) and to illustrate their application in the pricing of options. The topic is motivated by a desire to provide an intuitive understanding of certain probabilistic methods that have found significant use in financial economics. A rigorous presentation of the same ideas is presented briefly in Malliaris and Brock (1982) and more recently, Chalamandaris and Malliaris (2011). Itô’s Calculus was prompted by purely mathematical questions originating in Wiener’s work in 1923 on stochastic integrals and was developed by the Japanese probabilist Kiyosi Itô during 1944–1951. Two decades later economists such as Merton (1973) and Black and Scholes (1973) started using Itô’s stochastic differential equation to describe the behavior of asset prices. Because stochastic calculus is now used regularly by financial economists, some attention must be given to its mathematical meaning, its appropriateness in economic modeling, and its applications in economic modeling, and to finance

Assessment of the health status of Greek centenarians

The present study aims at describing the health status of a sample of relatively functional and healthy Greek centenarians and at exploring the potential gender differences in health in this sample. Its objectives are to add to the accumulation of knowledge about the health status of centenarians and therefore to contribute to the exploration of the mechanisms of healthy longevity. The study employs a non-representative community sample of Greek centenarians of both sexes (N = 47). It uses descriptive statistics in order to outline the health status of the participants and non-parametric tests to assess the statistical significance of the observed sex-differences. The study shows that the centenarians of our sample are relatively healthy and functional (15% of the sample was free of any major chronic disease). It also suggests, that the sex-difference in survival is statistical significant (p <= 0.013), and that the morbidity and co-morbidity rates of the Greek centenarians are relatively low (mean value of co-morbidity = 1.4 +/- 0.97, S.D.). Moreover, it provides valuable information on the anthropometric characteristics of the sample, and on health services utilization. These results indicate that exceptional longevity is not necessarily accompanied by disability, disease and total dependence on others. (C) 2007 Elsevier Ireland Ltd. All rights reserved

SET-bullying: presentation of a collaborative project and discussion of its internal and external validity

Background Since the early 1980s, several school based anti-bullying interventions (SBABI) have been implemented and evaluated in different countries. Some meta-analyses have also drawn conclusions on the effectiveness of SBABIs. However, the relationship between time and effectiveness of SBABIs has not been fully studied. For this aim, a collaborative project, SET-Bullying, is established by researchers from Greece, Belgium, Norway and United Kingdom. Its primary objective is to further understand and statistically model the relationship between the time and the sustainability of the effectiveness of SBABI. The secondary objective of SET-Bullying is to assess the possibility of predicting the medium-term or long-term effectiveness using as key information the prior measurement and the short-term effectiveness of the intervention. Results Researchers and owners of potentially eligible databases were asked to participate in this effort. Two studies have contributed data for the purpose of SET-Bullying. This paper summarizes the main characteristics of the participating studies and provides a high level overview of the collaborative project. It also discusses on the extent to which both study and project characteristics may pose threats to the expected internal and external validity of the potential outcomes of the project. Discussion Despite these threats, this work represents the first effort to understand the impact of time on the observed effectiveness of SBABIs and assess its predictability, which would allow for better planning, implementation and evaluation of SBABIs

Explanatory factors and causality in the dynamics of volatility surfaces implied from OTC Asian–Pacific currency options

Volatility implied from observed option contracts systematically varies with the contracts’ strike price and time to expiration, giving rise to an instantaneously non-flat implied volatility surface (IVS) that exhibits substantial time variation. We identify a number of latent factors that drive the dynamics of the IVSs from options on 11 Asian–Pacific exchange rates and show that these have a natural interpretation in the law of motion of each surface. We present evidence that these latent factors are related due to their common dependence on exogenous economy-wide variables. Findings suggest that the factors capturing (i) the volatility level of the Japanese yen and the Chinese yuan, (ii) the volatility term structure of the Japanese yen, Taiwanese and Australian dollars and (iii) the risk aversion towards the Australian dollar, Japanese yen and Chinese yuan seem to incorporate first the investors’ expectations regarding the volatility in the region

Diabetes mellitus, hypertension and hypercholesterolemia in relation to the 10-year ACS prognosis; the GREECS study

Although hypertension, hypercholesterolemia and diabetes mellitus (DM) are recognized as major cardio-metabolic risk factors in primary Acute Coronary Syndrome (ACS) prevention, studies focusing on secondary ACS incidence are scarce. In the present study, the association between the aforementioned factors and 10-year ACS prognosis was evaluated. From October 2003 to September 2004 2,172 consecutive patients with ACS diagnosis, from 6 Greek hospitals, were enrolled. During 2013-14, the 10-year follow-up was performed in 1,918 participants. Baseline clinical factors were assessed through physical examination, medical records and pharmacological management. All-cause mortality and the development of fatal or non-fatal ACS events were recorded through medical records or hospital registries. Logistic regression models were applied to evaluate the impact of baseline clinical status on the ACS prognosis. The 10-year all cause and ACS mortality rate was 32.6 and 17.8%, respectively. Multi-adjusted analysis highlighted that, after taking into account various potential confounders, DM was the sole clinical factor associated with adverse effect on the 10-year ACS fatal incidence [Odds Ratio (OR)=1.35, 95% Confidence Interval (95% CI) 1.01, 1.80, p=0.04]. DM was the only clinical factor that aggravated ACS prognosis, whereas abnormal lipids profile and blood pressure did not seem to determine prognosis. Thus, glycaemic control may play a critical role in the secondary CVD prevention management of ACS patients. © 2016 Bentham Science Publishers