Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer.

The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.

How Party Linkages Shape Austerity Politics: Clientelism and Fiscal Adjustment in Greece and Portugal during the Eurozone Crisis

Drawing on an analysis of austerity reforms in Greece and Portugal during the sovereign debt crisis from 2009 onwards, we show how the nature of the linkages between parties and citizens shapes party strategies of fiscal retrenchment. We argue that parties which rely to a greater extent on the selective distribution of state resources to mobilize electoral support (clientelistic linkages) are more reluctant to agree to fiscal retrenchment because their own electoral survival depends on their ability to control state budgets to reward clients. In Greece, where parties relied extensively on these clientelistic linkages, austerity reforms have been characterized by recurring conflicts and disagreements between the main parties, as well as a fundamental transformation of the party system. By contrast, in Portugal, where parties relied less on clientelistic strategies, austerity reforms have been more consensual because fiscal retrenchment challenged to a lesser extent the electoral base of the mainstream parties.

Välimiehen esteellisyys ja korvausvastuu

Tutkielman tarkoituksena oli välimiehen vastuun johtaminen korvausperusteen ollessa esteellisyys. Tutkielmassa paneuduttiin syvällisesti välimiehen asemaan, velvollisuuksiin, esteellisyyteen ja vastuun johtamiseen. Tutkimusmetodi oli lainopillinen systematisointi ja tulkinta, ja jossain määrin käsiteanalyysi. Tutkimusaineisto koostui ennakkopäätöksen KKO:2005:14 lisäksi suurimmalta osalta lakiartikkeleista ja -teksteistä. Tutkielmassa päädyttiin siihen johtopäätökseen, että välimiehen esteellisyys voi johtaa korvausvastuuseen, kun tuottamus ja syy-yhteys vahinkoon todetaan. Tuottamus voi KKO:2005:14 mukaisesti ilmetä myös velvollisuuden laiminlyöntinä. Tällaisena rikottuna velvoitteena toimi välimiesmenettelylain 9.2 §. Todettavissa on, ettei välimiehen korvausvastuun määrittyminen etenkin esteellisyyden kyseessä ollessa ole selkeää eikä yksioikoista.

Causality and contagion in peripheral EMU public debt markets: a dynamic approach

Our research aims to analyze the causal relationships in the behavior of public debt issued by peripheral member countries of the European Economic and Monetary Union -EMU-, with special emphasis on the recent episodes of crisis triggered in the eurozone sovereign debt markets since 2009. With this goal in mind, we make use of a database of daily frequency of yields on 10-year government bonds issued by five EMU countries -Greece, Ireland, Italy, Portugal and Spain-, covering the entire history of the EMU from its inception on 1 January 1999 until 31 December 2010. In the first step, we explore the pair-wise causal relationship between yields, both for the whole sample and for changing subsamples of the data, in order to capture the possible time-varying causal relationship. This approach allows us to detect episodes of contagion between yields on bonds issued by different countries. In the second step, we study the determinants of these contagion episodes, analyzing the role played by different factors, paying special attention to instruments that capture the total national debt -domestic and foreign- in each country.

Forward Looking Banking Stress in EMU Countries

Based on contingent claims analysis, CCA, this paper tries to estimate the systemic risk build-up in the European Economic and Monetary Union, EMU countries using a market based measure distance-to-default, DtD. It analyzes the individual and aggregated series for a comprehensive set of banks in each eurozone country over the period 2004-Q4 to 2013-Q2. Given the structural differences in financial sector and banking regulations at national level, the indices provide a useful indicator for monitoring country specific banking vulnerability and stress. We find that average DtD indicators are intuitive, forward-looking and timely risk indicators. The underlying trend, fluctuations and correlations among indices help us analyze the interdependence while cross-sectional differences in DtD prior to crisis suggest banking sector fragility in peripheral EMU countries.

How institutions shaped the last major evolutionary transition to large-scale human societies.

What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter-gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization.

Nouvelle jurisprudence concernant le traitement des subventions au regard de la TVA

La Commission fédérale de recours en matière de contributions (ci-après «CRC») vient de rendre deux décisions relatives à la TVA en matière de subventions et leur impact sur la récupération de l'impôt préalable. Ces deux jugements s'inscrivent dans la ligne de la jurisprudence de la CRC en matière de subventions. Ils conduisent à un résultat conforme au principe même de la TVA, en ce sens que, selon le type de subventions, leur traitement TVA et en particulier leur influence sur le droit à la récupération de l’impôt préalable varie. Ces deux jugements ont toutefois une portée plus large que pour les seules subventions. En effet, le projet de loi sur la TVA qui reprend la réglementation prévue dans l’OTVA, applique le même traitement aux dons. Compte tenu de l’importance des concepts relatifs aux subventions développés dans les deux décisions de la CRC, il nous a paru opportun de retranscrire de manière détaillée les considérants des deux décisions, avant d’ajouter quelques remarques et commentaires sur ces deux arrêts et de les mettre en relation avec le projet de loi sur la TVA.

Sovereigns and banks in the euro area : a tale of two crises

This study attempts to identify and trace inter-linkages between sovereign and banking risk in the euro area. To this end, we use an indicator of banking risk in each country based on the Contingent Claim Analysis literature, and 10-year government yield spreads over Germany as a measure of sovereign risk. We apply a dynamic approach to testing for Granger causality between the two measures of risk in 10 euro area countries, allowing us to check for contagion in the form of a significant and abrupt increase in short-run causal linkages. The empirical results indicate that episodes of contagion vary considerably in both directions over time and within the different EMU countries. Significantly, we find that causal linkages tend to strengthen particularly at the time of major financial crises. The empirical evidence suggests the presence of contagion, mainly from banks to sovereigns.

Kirjallisuutta

Kirjallisuusarvostelu

Metaanin muodostumisen mallintaminen kaatopaikalla

Methane-rich landfill gas is generated when biodegradable organic wastes disposed of in landfills decompose under anaerobic conditions. Methane is a significant greenhouse gas, and landfills are its major source in Finland. Methane production in landfill depends on many factors such as the composition of waste and landfill conditions, and it can vary a lot temporally and spatially. Methane generation from waste can be estimated with various models. In this thesis three spreadsheet applications, a reaction equation and a triangular model for estimating the gas generation were introduced. The spreadsheet models introduced are IPCC Waste Model (2006), Metaanilaskentamalli by Jouko Petäjä of Finnish Environment Institute and LandGEM (3.02) of U.S. Environmental Protection Agency. All these are based on the first order decay (FOD) method. Gas recovery methods and gas emission measurements were also examined. Vertical wells and horizontal trenches are the most commonly used gas collection systems. Emission measurements chamber method, tracer method, soil core and isotope measurements, micrometeorological mass-balance and eddy covariance methods and gas measuring FID-technology were discussed. Methane production at Ämmässuo landfill of HSY Helsinki Region Environmental Services Authority was estimated with methane generation models and the results were compared with the volumes of collected gas. All spreadsheet models underestimated the methane generation at some point. LandGEM with default parameters and Metaanilaskentamalli with modified parameters corresponded best with the gas recovery numbers. Reason for the differences between evaluated and collected volumes could be e.g. that the parameter values of the degradable organic carbon (DOC) and the fraction of decomposable degradable organic carbon (DOCf) do not represent the real values well enough. Notable uncertainty is associated with the modelling results and model parameters. However, no simple explanation for the discovered differences can be given within this thesis.

On the institution of the moral subject: on the commander and the commanded in Nietzsche's discussion of law

The article discusses how Nietzsche understands the institution of law and morals in distinction to Kant and the Christian tradition. It argues that Nietzsche to a large extent is inspired by the paradigm-shift toward a evolutionary biological thinking introduced by several of his peers in the late 19th century, among else F. A. Lange, who sees this shift as a sobering scientific-materialistic alternative to Kant. In Nietzsche, the Kantian moral imperative is replaced with a notion of a morality emerging thanks to historical, or pre-historical, civilizational processes, imposed on a feebleminded human without any inherent rational dispositions to obey Law. It is also a process, which rather than universalizing the human, splits it in a duality where one part obeys old immediate self-interests and another part obeys new 'commands,' having been shouted 'into the ear' by a so-called 'commander.' The compliance with law takes two radically different forms in Nietzsche: servile and mediocre individuals need to be exposed to discipline and punishment in order to adopt Law; while so-called 'sovereign' individuals are able to impose law upon themselves. The figure of the 'sovereign' has consequently been an issue for vigorous debate in especially the Anglo-Saxon tradition of Nietzsche research, since his apparent 'respect for law' and 'sense of duty' reiterate typical Kantian qualities. Relating to these discussions, I suggest that Nietzsche's 'sovereign' (in one context) is identical his 'commander' (in other contexts). When the 'sovereign' as such imposes law upon himself and others, his act is conventional and arbitrary (like language in Saussure), and is rather irrational than rational as in Kant. His will is not a good will, nor a rational will with a vision of human autonomy. His command of himself and others is a performative, thus without truth-value (like illocutionary speech-acts in Austin and Searle).

Image analysis for assessing broiler breeder behavior response to thermal environment

The research proposes a methodology for assessing broiler breeder response to changes in rearing thermal environment. The continuous video recording of a flock analyzed may offer compelling evidences of thermal comfort, as well as other indications of welfare. An algorithm for classifying specific broiler breeder behavior was developed. Videos were recorded over three boxes where 30 breeders were reared. The boxes were mounted inside an environmental chamber were ambient temperature varied from cold to hot. Digital images were processed based on the number of pixels, according to their light intensity variation and binary contrast allowing a sequence of behaviors related to welfare. The system used the default of x, y coordinates, where x represents the horizontal distance from the top left of the work area to the point P, and y is the vertical distance. The video images were observed, and a grid was developed for identifying the area the birds stayed and the time they spent at that place. The sequence was analyzed frame by frame confronting the data with specific adopted thermal neutral rearing standards. The grid mask overlapped the real bird image. The resulting image allows the visualization of clusters, as birds in flock behave in certain patterns. An algorithm indicating the breeder response to thermal environment was developed.