Last of Its Kind: The Review of the Technology Transfer Block Exemption Regulation, The Symposium on European Competition Law

On October 1, 2003, the Commission published a formal proposal for a new technology transfer block exemption ( Draft TTBE ) together with detailed draft guidelines ( Draft Guidelines )5 which explain how the new regulation will be interpreted and how Article 81 will be applied to agreements that fall outside the revised regulation\u27s safe harbor. These proposals unleashed a barrage of criticism from industry and seem likely to result in some amendments to the proposed texts before their adoption in March or April 2004. The new package is due to enter into force on May 1, 2004. This article discusses the Commission\u27s proposals for reform as published in October 2003. We indicate the major changes that are likely to be introduced to this package as envisaged in a revised text circulated by the Commission to the Member States in January 2004 but which, regrettably, will not be made publicly available for further consultation. Although the final package may be subject to further amendment before it is finally adopted, it is encouraging that the Commission seems to have taken on board many of the industry\u27s concerns and is currently envisaging a more flexible regulatory environment than was originally foreseen

Dual pathway inhibition for atherosclerotic cardiovascular disease: Recent advances

Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease (CAD), cerebrovascular disease, and peripheral arterial disease (PAD) is associated with significant morbidity, mortality, and healthcare costs. Antiplatelet therapy has long been the mainstay of antithrombotic therapy for the prevention of first-ever and recurrent ASCVD events. More recently, however, randomized trials have demonstrated the benefits and cost-effectiveness of a dual pathway inhibition (DPI) strategy in acute and chronic ASCVD. When used in combination, aspirin and low-dose rivaroxaban work synergistically to inhibit platelet activation and thrombin generation, thereby preventing thrombus formation. Among patients with recent acute coronary syndrome (ACS), those with positive cardiac biomarkers or ST-segment elevation myocardial infarction, or a history of heart failure derive the greatest absolute benefits. Among patients with chronic ASCVD, those with involvement of two or more vascular beds, heart failure, chronic kidney disease, or diabetes derive the greatest absolute benefits. Additional trials are underway to assess the impact of DPI therapy in other populations of interest, including patients with ACS at high risk of left ventricular thrombus formation, intracranial atherosclerotic disease with recent transient ischemic attack or stroke, peripheral arterial disease with limiting claudication or post lower extremity revascularization, and advanced chronic kidney disease with ASCVD or risk factors for ASCVD. Further work is required to assess the possible added benefit of combining rivaroxaban with clopidogrel or ticagrelor instead of aspirin

Dwukierunkowe hamowanie w miażdżycy układu sercowo-naczyniowego — ostatnie postępy

Choroba układu sercowo-naczyniowego o podłożu miażdżycy (ASCVD, atherosclerotic cardiovascular disease), która obejmuje chorobę wieńcową (CAD, coronary artery disease), chorobę naczyń mózgowych oraz chorobę tętnic obwodowych (PAD, peripheral arterial disease), wiąże się z dużą zachorowalnością, śmiertelnością i kosztami opieki zdrowotnej. Terapia przeciwpłytkowa była od dawna podstawą leczenia przeciwzakrzepowego w profilaktyce pierwszych i ponownych incydentów ASCVD. Jednak ostatnie randomizowane badania pokazały zalety i efektywność kosztową strategii dwukierunkowego hamowania (DPI, dual pathway inhibition) w ostrej i przewlekłej ASCVD. Kwas acetylosalicylowy stosowany w skojarzeniu z małą dawką rywaroksabanu działają synergistycznie, hamując aktywację płytek krwi i generację trombiny, tym samym zapobiegając powstawaniu skrzepliny. Wśród pacjentów z niedawnym ostrym zespołem wieńcowym (ACS, acute coronary syndrome), ci z dodatnimi biomarkerami sercowymi, zawałem serca z uniesieniem odcinka ST lub historią niewydolności serca odnoszą największe bezwzględne korzyści. Wśród pacjentów z przewlekłą ASCVD, ci z zajęciem dwóch lub więcej łożysk naczyniowych, niewydolnością serca, przewlekłą chorobą nerek lub cukrzycą odnoszą największe bezwzględne korzyści. Dodatkowe badania są w trakcie realizacji, celem oceny wpływu terapii DPI w innych interesujących populacjach, w tym pacjentów z ACS z dużym ryzykiem powstania skrzepliny w lewej komorze, wewnątrzczaszkową miażdżycą tętnic po niedawno przebytym przemijającym napadzie niedokrwienia mózgu lub udarze, chorobą tętnic obwodowych z chromaniem przestankowym lub po rewaskularyzacji kończyn dolnych i zaawansowaną przewlekłą chorobą nerek z ASCVD lub czynnikami ryzyka ASCVD. Dalsze badania są potrzebne w celu oceny możliwych dodatkowych korzyści z łączenia rywaroksabanu z klopidogrelem lub tikagrelorem zamiast kwasu acetylosalicylowego

Observed intra-cluster correlation coefficients in a cluster survey sample of patient encounters in general practice in Australia

BACKGROUND: Cluster sample study designs are cost effective, however cluster samples violate the simple random sample assumption of independence of observations. Failure to account for the intra-cluster correlation of observations when sampling through clusters may lead to an under-powered study. Researchers therefore need estimates of intra-cluster correlation for a range of outcomes to calculate sample size. We report intra-cluster correlation coefficients observed within a large-scale cross-sectional study of general practice in Australia, where the general practitioner (GP) was the primary sampling unit and the patient encounter was the unit of inference. METHODS: Each year the Bettering the Evaluation and Care of Health (BEACH) study recruits a random sample of approximately 1,000 GPs across Australia. Each GP completes details of 100 consecutive patient encounters. Intra-cluster correlation coefficients were estimated for patient demographics, morbidity managed and treatments received. Intra-cluster correlation coefficients were estimated for descriptive outcomes and for associations between outcomes and predictors and were compared across two independent samples of GPs drawn three years apart. RESULTS: Between April 1999 and March 2000, a random sample of 1,047 Australian general practitioners recorded details of 104,700 patient encounters. Intra-cluster correlation coefficients for patient demographics ranged from 0.055 for patient sex to 0.451 for language spoken at home. Intra-cluster correlations for morbidity variables ranged from 0.005 for the management of eye problems to 0.059 for management of psychological problems. Intra-cluster correlation for the association between two variables was smaller than the descriptive intra-cluster correlation of each variable. When compared with the April 2002 to March 2003 sample (1,008 GPs) the estimated intra-cluster correlation coefficients were found to be consistent across samples. CONCLUSIONS: The demonstrated precision and reliability of the estimated intra-cluster correlations indicate that these coefficients will be useful for calculating sample sizes in future general practice surveys that use the GP as the primary sampling unit

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Human-correlated genetic HCC models identify combination therapy for precision medicine [Pre-print]

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer related mortality worldwide. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulated progressive driver mutations, with hepatocytes the most likely cell of origin. However, the landscape of driver mutations in HCC is independent of the underlying aetiologies. Despite an increasing range of systemic treatment options for advanced HCC outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations. Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC. We generated over twenty-five new genetically-driven in vivo and in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance, and metastasis to distant organs. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with histopathology. In a proof-of-principle analysis, we verified response to standard of care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not been linked to HCC treatment before. Cladribine acts in a highly effective subtype-specific manner in combination with standard of care therapy

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI