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.

Internationalization dynamics in the Swiss Corporate Tax Reform III

Over the last years, in a context of international tax competition, international and regional institutions such as the G20, the OECD, and the European Union are redefining what is acceptable in terms of corporate fiscal policy. Certain Swiss preferential tax treatments are considered by the above-mentioned institutions as harmful tax practices. As a consequence, the Swiss government has planned a third corporate tax reform (CTR III). The objective of this reform is to ensure international acceptability of the corporate tax system without prejudicing local public finances and Swiss corporate tax attractiveness. Therefore, we can posit that the CTR III is an internationalized object influenced by both regulation trends and tax competition framework. The main purpose of this paper is to provide elements of answer on how the currently discussed CTR III is influenced by the international environment, by focusing on its content as well as the reactions and positions of local stakeholders. With the help of internationalization literature, two distinct internationalization processes have been identified through the propositions of compliance measures with internationally-defined standards and competitiveness-enhancing measures. With regard to the configuration of local actors, the degree of conflict seems to be rather high. The current content of the reform is supported by the business community and right-wing parties and rejected by the unions and the Socialist Party.

Capability matrix – Identifying and evaluating the key capabilities of purchasing and supply management

Organizations gain resources, skills and technologies to find out the ultimate mix of capabilities to be a winner in the competitive market. These are all important factors that need to be taken into account in organizations operating in today's business environment. So far, there are no significant studies on the organizational capabilities in the field of PSM. The literature review shows that the PSM capabilities need to be studied more comprehensively. This study attempts to reveal and fill this gap by providing the PSM capability matrix that identifies the key PSM capabilities approached from two angles: there are three primary PSM capabilities and nine subcapabilities and, moreover, the individual and organizational PSM capabilities are identified and evaluated. The former refers to the PSM capability matrix of this study which is based on the strategic and operative PSM capabilities that complement the economic ones, while the latter relates to the evaluation of the PSM capabilities, such as the buyer profiles of individual PSM capabilities and the PSMcapability map of the organizational ones. This is a constructive case study. The aim is to define what the purchasing and supply management capabilities are and how they can be evaluated. This study presents a PSM capability matrix to identify and evaluate the capabilities to define capability gaps by comparing the ideal level of PSM capabilities to the realized ones. The research questions are investigated with two case organizations. This study argues that PSM capabilities can be classified into three primary categories with nine sub-categories and, thus, a PSM capability matrix with four evaluation categories can be formed. The buyer profiles are moreover identified to reveal the PSM capability gap. The resource-based view (RBV) and dynamic capabilities view (DCV) are used to define the individual and organizational capabilities. The PSM literature is also used to define the capabilities. The key findings of this study are i) the PSM capability matrix to identify the PSM capabilities, ii) the evaluation of the capabilities to define PSM capability gaps and iii) the presentation of the buyer profiles to identify the individual PSM capabilities and to define the organizational PSM capabilities. Dynamic capabilities are also related to the PSM capability gap. If a gap is identified, the organization can renew their PSM capabilities and, thus, create mutual learning and increase their organizational capabilities. And only then, there is potential for dynamic capabilities. Based on this, the purchasing strategy, purchasing policy and procedures should be identified and implemented dynamically.

John Ruskin. Paysages de pierres

L'article analyse une aquarelle de John Ruskin intitulée "Bay of Uri, Lake Lucern" (1858) et évoque d'autres oeuvres de Ruskin présentées dans l'exposition de la Fondation Pierre Arlaud à Lens (Valais, Suisse) durant l'hiver 2015-2016. Il montre l'importance de la méditation sur les pierres dans la pensée de Ruskin.

Poland 's syndrome: radiologic findings

Poland's syndrome is a rare non-inherited congenital anomaly. The authors describe the classic radiologic findings of Poland's syndrome by reporting the case of a male four-year old patient with asymmetry of hands and chest, illustrating the fundamental imaging criteria for a conclusive diagnosis.

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Online and Offline Participation at the Local Level : A Quantitative Analysis of the Catalan Municipalities

This paper presents a first analysis on local electronic participatory experiences in Catalonia. The analysis is based on a database constructed and collected by the authors. The paper carries out an explanatory analysis of local initiatives in eparticipationand off line participation taking into account political variables (usually not considered in this kind of analysis) but also classical socio-economic variables that characterise municipalities. Hence, we add a quantitative analysis to the numerous case studies on local e-participation experiences. We have chosen Catalonia because is one of the European regions with more initiatives and one that has enjoyed considerable local governmental support to citizen participation initiatives since the 80s. The paper offers a characterisation of these experiences and a first explanatory analysis, considering: i) the institutional context in which these experiences are embedded, ii) the characteristics of the citizen participation processes and mechanisms on-line, and iii) a set of explanatory variables composed by the population size, thepolitical adscription of the mayor, the electoral abstention rate, age, income and level ofeducation in the municipality. The model that we present is explanatory for the municipalities with more than 20,000 inhabitants but it is not for the fewer than 20,000inhabitants. Actually, the number of participatory activities developed by these last municipalities is very low. Among all the variables, population size becomes the mostinfluential variable. Political variables such as political party of the mayor and the localabstention rate have a certain influence but that have to be controlled by population size.

Estudo polarográfico sobre a determinação de Fe(III) utilizando-se a técnica da polarografia de pulso diferencial

A differential pulse polarographic study with the objective to determine iron (III) in presense of copper (II) in a supporting electrolyte based on citrate - EDTA was made. The best experimental conditions found were a supporting electrolyte of citrate 0.25 mol L-1, EDTA 0.050 mol L-1 and KNO3 0.50 mol L-1, pH 5.00. In this media iron (III) showed a polarographic peak in -0.08 V and the copper (II) in -0.34 V, both vs. Ag/AgCl (saturated KCl). Thus, a analytical method was developed and applied to determine iron (III) in brass alloy, a matrix were copper is in large excess over iron. The results obtained showed no interference of copper in the iron determination. The value of 0.21% of iron in the sample alloy composition was obtained and the method was validated by atomic absortion and recovery test, and the results exhibited a good agreement with the proposed method.

Research of wood fuel market in Ukraine and the Republic of Belarus

The goal of the present work was to describe the wood fuel market of Ukraine and the Republic of Belarus, to estimate wood fuel potential and to research opportunities of wood fuel trading. Nowadays the wood waste, wood residues and by-products are becoming more and more potential raw materials for energy production. Against the background of unstable prices of traditional energy sources and environmental degradation, European States are planning to get 12% of energy from alternative sources already in 2010. Wastes of wood-working and agricultural productions are such sources. At present time the most popular wood biofuels are wood pellets, briquettes, wood chips and logs. Ukraine and the Republic of Belarus have a rather big potential of wood fuel resources. But wood fuels markets of these countries are on the entry level and quite disorganized. There is almost no domestic usage of wood biofuel. All produced pellets, briquettes as well as wood chips and logs go to the export, but the volumes are not high at present time. Ukraine and the Republic of Belarus have a very suitable geographical location. The most promising directions of wood fuel trading are developed wood fuel markets of Northern countries, Austria, Germany as well as actively developing markets of Poland and Hungary. At the long distance truck and sea transportation are the most appropriate. At a short distance cheap transportation by rail is more suitable. Thereby export is a potential opportunity for development of wood fuel production and in the future for usage in the researched countries.

Óxido misto de ítrio-alumínio dopado com Eu(III)

In this work, we report the synthesis and the photoluminescence features of Eu(III)-doped yttrium-aluminium oxide obtained by non-hydrolytic sol-gel routes. After heating the powders above 600 ºC the XRD patterns show the presence of the Y4Al2O9 (YAM) and Y3Al5O12 (YAG) phases. At 800 and at 1500 ºC the PL spectra display the Eu(III) lines characteristic of the YAM monoclinic phase. The 5D0->7F2 transition is favored relatively to the 5D0->7F1 lines. However, at 1100 ºC the cubic YAG is the preferential phase and the 5D0->7F1 transition dominates the spectrum. The Eu(III) ions lie in a centrosymmetrical site. The different solvents used in the sol-gel synthesis also change the relative proportion between these two phases. This is monitored analyzing the modifications in the relative intensity between the 5D0->7F2 and the 5D0->7F1 transitions.

Fenilsilicato dopado com Eu III obtido pelo método sol-gel

In this work, we report the synthesis and the photoluminescence features of a Eu(III)-doped modified silica matrix obtained by the sol-gel method. The matrix was prepared by reaction between tetraethylorthosilicate and phenyltriethoxysilane alkoxide. The hydrolysis occurred using basic catalysis. The solids were treated at 100, 200 and 300 ºC during 4 h and the structure was determined by thermogravimetric analysis (TG/DTG), nuclear magnetic resonance (NMR 29Si and 13C), infrared spectroscopy (IR) and photoluminescence (PL). The PL spectra display the Eu(III) lines characteristic of the ion, 5D0 -> 7F J (J=0, 1, 2, 3, 4), the blue emission as ascribed in the silica matrix. The NMR and TG showed the stability of hybrid silica.

Conservation Genetics of Exploited Finnish Salmonid Fishes

Genetic diversity is one of the levels of biodiversity that the World Conservation Union (IUCN) has recognized as being important to preserve. This is because genetic diversity is fundamental to the future evolution and to the adaptive flexibility of a species to respond to the inherently dynamic nature of the natural world. Therefore, the key to maintaining biodiversity and healthy ecosystems is to identify, monitor and maintain locally-adapted populations, along with their unique gene pools, upon which future adaptation depends. Thus, conservation genetics deals with the genetic factors that affect extinction risk and the genetic management regimes required to minimize the risk. The conservation of exploited species, such as salmonid fishes, is particularly challenging due to the conflicts between different interest groups. In this thesis, I conduct a series of conservation genetic studies on primarily Finnish populations of two salmonid fish species (European grayling, Thymallus thymallus, and lake-run brown trout, Salmo trutta) which are popular recreational game fishes in Finland. The general aim of these studies was to apply and develop population genetic approaches to assist conservation and sustainable harvest of these populations. The approaches applied included: i) the characterization of population genetic structure at national and local scales; ii) the identification of management units and the prioritization of populations for conservation based on evolutionary forces shaping indigenous gene pools; iii) the detection of population declines and the testing of the assumptions underlying these tests; and iv) the evaluation of the contribution of natural populations to a mixed stock fishery. Based on microsatellite analyses, clear genetic structuring of exploited Finnish grayling and brown trout populations was detected at both national and local scales. Finnish grayling were clustered into three genetically distinct groups, corresponding to northern, Baltic and south-eastern geographic areas of Finland. The genetic differentiation among and within population groups of grayling ranged from moderate to high levels. Such strong genetic structuring combined with low genetic diversity strongly indicates that genetic drift plays a major role in the evolution of grayling populations. Further analyses of European grayling covering the majority of the species’ distribution range indicated a strong global footprint of population decline. Using a coalescent approach the beginning of population reduction was dated back to 1 000-10 000 years ago (ca. 200-2 000 generations). Forward simulations demonstrated that the bottleneck footprints measured using the M ratio can persist within small populations much longer than previously anticipated in the face of low levels of gene flow. In contrast to the M ratio, two alternative methods for genetic bottleneck detection identified recent bottlenecks in six grayling populations that warrant future monitoring. Consistent with the predominant role of random genetic drift, the effective population size (N_e) estimates of all grayling populations were very low with the majority of N_e estimates below 50. Taken together, highly structured local populations, limited gene flow and the small N_e of grayling populations indicates that grayling populations are vulnerable to overexploitation and, hence, monitoring and careful management using the precautionary principles is required not only in Finland but throughout Europe. Population genetic analyses of lake-run brown trout populations in the Inari basin (northernmost Finland) revealed hierarchical population structure where individual populations were clustered into three population groups largely corresponding to different geographic regions of the basin. Similar to my earlier work with European grayling, the genetic differentiation among and within population groups of lake-run brown trout was relatively high. Such strong differentiation indicated that the power to determine the relative contribution of populations in mixed fisheries should be relatively high. Consistent with these expectations, high accuracy and precision in mixed stock analysis (MSA) simulations were observed. Application of MSA to indigenous fish caught in the Inari basin identified altogether twelve populations that contributed significantly to mixed stock fisheries with the Ivalojoki river system being the major contributor (70%) to the total catch. When the contribution of wild trout populations to the fisheries was evaluated regionally, geographically nearby populations were the main contributors to the local catches. MSA also revealed a clear separation between the lower and upper reaches of Ivalojoki river system – in contrast to lower reaches of the Ivalojoki river that contributed considerably to the catch, populations from the upper reaches of the Ivalojoki river system (>140 km from the river mouth) did not contribute significantly to the fishery. This could be related to the available habitat size but also associated with a resident type life history and increased cost of migration. The studies in my thesis highlight the importance of dense sampling and wide population coverage at the scale being studied and also demonstrate the importance of critical evaluation of the underlying assumptions of the population genetic models and methods used. These results have important implications for conservation and sustainable fisheries management of Finnish populations of European grayling and brown trout in the Inari basin.

Rejeito de mineração de carvão como adsorvente para remoção da acidez, Fe (III), Al (III) e Mn (II) em drenagem ácida

This study aimed the use of coal mining waste as a new adsorbent for H3O+ and removal of Al (III), Fe (III) and Mn (II) from acid mine drainage. Data from kinetic and equilibrium of the adsorption of H3O+ followed the pseudo second-order and Langmuir isotherm models. The maximum adsorption capacity of H3O+ was 316 mmol kg-1. The adsorbent removed 100% of Al (III), 100% of Fe (III) and 89% of Mn (II), suggesting its use as an alternative for the treatment of acid mine drainage.

Highly improved chromium (III) uptake capacity in modified sugarcane bagasse using different chemical treatments

The present paper focuses on improving chromium (III) uptake capacity of sugarcane bagasse through its chemical modification with citric acid and/or sodium hydroxide. The chemical modifications were confirmed by infrared spectroscopy, with an evident peak observed at 1730 cm-1, attributed to carbonyl groups. Equilibrium was reached after 24 h, and the kinetics followed the pseudo-second-order model. The highest chromium (III) maximum adsorption capacity (MAC) value was found when using sugarcane bagasse modified with sodium hydroxide and citric acid (58.00 mg g-1) giving a MAC value about three times greater (20.34 mg g-1) than for raw sugarcane bagasse.

Composition of Hawthorn (Crataegus spp.) Fruits and Leaves and emblic Leafflower (Phyllanthus emblica) Fruits

Hawthorn (Crataegus sp.) is widely distributed in the northern hemisphere (Asia, Europe and North America). It has been used as a medicinal material and food for hundreds of years both in Europe and in China. Clinical investigations and other research suggest that extracts of hawthorn fruits and leaves have multiple health effects including hypolipidaemic, anti-atherosclerotic, hypotensive, cardioprotective and blood vessel relaxing activities. Hawthorn fruit extracts have also displayed antioxidant and radical scavenging activities. Emblic leafflower fruit (Phyllanthus emblica) is widely used in Chinese and Indian traditional medicine. It has been found to have anti-cancer, hypoglycaemic and hypolipidaemic activities as well as cardioprotective effects and antioxidant activity. The fruit is currently used as a functional food targeted at obese people in China. Phenolic compounds, procyanidins (PCs), flavonols and C-glycosyl flavones in hawthorn and hydrolysable tannins in emblic leafflower fruits are considered among the major bioactive compounds in these berries. Moreover, hawthorn and emblic leafflower fruits are rich in vitamin C, triterpenoids, fruit acids, sugar alcohols and some other components with beneficial effects on the health of human beings. The aim of the thesis work was to characterise the major phenolic compounds in hawthorn fruits and leaves and emblic leafflower fruits as well as other components contributing to the nutritional profile and sensory properties of hawthorn fruits. Differences in the content and compositional profile of the major phenolic compounds, sugars, acids and sugar alcohols within various origins and species of hawthorn were also investigated. Acids, sugars and sugar alcohols in the fruits of different origins/cultivars belonging to three species (C. pinnatifida, C. brettschneideri and C. scabrifolia) of hawthorn were analysed by gas chromatography (GC-FID) and mass spectrometry (Publication I). Citric acid, quinic acid, malic acid, fructose, glucose, sorbitol and myo-inositol were found in all the subspecies. Sucrose was present only in C. scabrifolia and three cultivars of C. pinnatifida var. major. Forty-two phenolic compounds were identified/tentatively identified in fruits of C. pinnatifida var. major by polyamide column chromatography combined with high-performance liquid chromatograph-electrospray ionisation mass spectrometry (HPLC-ESI-MS) (Publication II). Ideain, chlorogenic acid, procyanidin (PC) B2, (-)-epicatechin, hyperoside and isoquercitrin were the major phenolic components identified. In addition, 35 phenolic compounds were tentatively identified based on UV and mass spectra. Eleven major phenolic compounds (hyperoside, isoquercitrin, chlorogenic acid, ideain, (-)-epicatechin, two PC dimers, three PC trimers and a PC dimer-hexoside) were quantified in the fruits of 22 cultivars/origins of three species of Chinese hawthorn by HPLC-ESI-MS with single ion recording function (SIR) (Publication III). The fruits of the hawthorn cultivars/origins investigated fell into two groups, one rich in sugars and flavonols, the other rich in acids and procyanidins. Based on the compositional features, different biological activities and sensory properties may be expected between cultivars/origins of the two groups. The results suggest that the contents of phenolic compounds, acids, sugars and sugar alcohols may be used as chemotaxonomic information distinguishing the hawthorn species from each other. Phenolic compounds in fruits and leaves of C. grayana and their changes during fruit ripening/harvesting were investigated using HPLC-UV-ESI-MS (Publication IV). (-)-Epicatechin, PC B2 and C1, hyperoside and a quercetin-pentoside were the major phenolic compounds in both fruits and leaves. Three C-glycosyl flavones (a luteolin-C-hexoside, a methyl luteolin-C-hexoside and an apigenin-C-hexoside) were present in leaves in abundance, but only at trace levels in fruits. Ideain and 5-O-caffeoylquinic acid were found in fruits only. Additionally, eleven phenolic compounds were identified/tentatively identified in both leaves and fruits (three B-type PC trimers, two B-type PC tetramers, a quercetin-rhamnosylhexoside, a quercetin-pentoside, a methoxykaempferol-methylpentosylhexoside, a quercetin-hexoside acetate, a methoxykaempferol-pentoside, chlorogenic acid and an unknown hydroxycinnamic acid derivative). The total content of phenolic compounds reached the highest level by the end of August in fruits and by the end of September in leaves. The compositional profiles of phenolic compounds in fruits and leaves of C. grayana were different from those of C. pinnatifida, C. brettschneideri, C. scabrifolia, C. pinnatifida. var. major, C. monogyna, C. laevigata and C. pentagyna. Phenolic compounds in emblic leafflower fruits were characterised by Sephadex LH-20 column chromatography combined with HPLC-ESI-MS (Publication V). A mucic acid gallate, three isomers of mucic acid lactone gallate, a galloylglucose, gallic acid, a digalloylglucose, putranjivain A, a galloyl-HHDP-glucose, elaeocarpusin and chebulagic acid represented the major phenolic compounds in fruits of emblic leafflower. In conclusion, results of this study significantly increase the current knowledge on the key bioactive and nutritional components of hawthorn and emblic leafflower fruits. These results provide important information for research on the mechanism responsible for the health benefits of these fruits.