Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

The Application of a Pluralist Approach of Global Administrative Law on the Governance of Doping in Sport

Plusieurs problèmes liés à l'utilisation de substances et méthodes interdites de dopage dans les sports posent de grands défis à la gouvernance antidopage. Afin de lutter contre le dopage, certains pays ont mis en oeuvre des cadres juridiques basés exclusivement sur le droit pénal tandis que d'autres pays ont plutôt misé sur des mécanismes et organismes spécialisés trouvant fondement en droit privé ou sur un régime hybride de droit public et privé. Ces différentes approches réglementaires ont pour conséquence de faire en sorte qu’il est très difficile de lutter efficacement contre le dopage dans les sports, notamment parce que leur exécution requiert un degré de collaboration internationale et une participation concertée des autorités publiques qui est difficile à mettre en place. À l’heure actuelle, on peut par exemple observer que les États n’arrivent pas à contrer efficacement la participation des syndicats et organisations transnationales liés au crime organisé dans le marché du dopage, ni à éliminer des substances et méthodes de dopage interdites par la réglementation. Par ailleurs, la gouvernance antidopage basée sur les règles prescrites par l’Agence mondiale antidopage prévoit des règles et des normes distinctes de dopage distinguant entre deux catégories de personnes, les athlètes et les autres, plaçant ainsi les premiers dans une position désavantageuse. Par exemple, le standard de responsabilité stricte sans faute ou négligence imposé aux athlètes exige moins que la preuve hors de tout doute raisonnable et permet l'utilisation de preuves circonstancielles pour établir la violation des règles antidopages. S'appliquant pour prouver le dopage, ce standard mine le principe de la présomption d'innocence et le principe suivant lequel une personne ne devrait pas se voir imposer une peine sans loi. D’ailleurs, le nouveau Code de 2015 de l’Agence attribuera aux organisations nationales antidopage (ONADs) des pouvoirs d'enquête et de collecte de renseignements et ajoutera de nouvelles catégories de dopage non-analytiques, réduisant encore plus les droits des athlètes. Dans cette thèse, nous discutons plus particulièrement du régime réglementaire de l’Agence et fondé sur le droit privé parce qu’il ne parvient pas à répondre aux besoins actuels de gouvernance mondiale antidopage. Nous préconisons donc l’adoption d’une nouvelle approche de gouvernance antidopage où la nature publique et pénale mondiale du dopage est clairement reconnue. Cette reconnaissance combiné avec un modèle de gouvernance adapté basé sur une approche pluraliste du droit administratif global produira une réglementation et une administration antidopage mieux acceptée chez les athlètes et plus efficace sur le plan des résultats. Le nouveau modèle de gouvernance que nous proposons nécessitera toutefois que tous les acteurs étatiques et non-étatiques ajustent leur cadre de gouvernance en tenant compte de cette nouvelle approche, et ce, afin de confronter les défis actuels et de régler de manière plus satisfaisante les problèmes liés à la gouvernance mondiale du dopage dans les sports.

Local food security and principle of organic farming (from farm to fork) in context of food culture in Indonesia: Minangkabau's case study

The basic idea behind improving local food security consists of two paths; first, accessibility (price, stock) and second, availability (quantity and biodiversity); both are perquisites to the provision of nutrients and a continuous food supply with locally available resources. The objectives of this thesis are to investigate if indigenous knowledge still plays an important role in traditional farming in the Minangkabau`s culture, thus supporting local food security. If the indigenous knowledge still plays a role in food culture in the Minangkabau`s culture which is linked to the matrilineal role and leads to a sound nutrition. Further, it should be tested if marantau influences traditional farming and food culture in Minangkabau`s, and if the local government plays a role in changing of traditional farming systems and food culture. Furthermore this thesis wants to prove if education and gender are playing a role in changing traditional farming system and food culture, and if the mass media affects traditional farming systems and food culture for the Minangkabau. The study was completed at four locations in West Sumatera; Nagari Ulakan (NU) (coastal area), Nagari Aia Batumbuak (NAB) (hilly area), Nagari Padang Laweh Malalo (NPLM) (lake area), Nagari Pandai Sikek (NPS) (hilly area). The rainfall ranged from 1400- 4800 mm annually with fertile soils. Data was collected by using PRA (Participatory Rural Appraisal) to investigate indigenous knowledge (IK) and its interactions, which is also combining with in depth-interview, life history, a survey using semi-structured-questionnaire, pictures, mapping, and expert interview. The data was collected from June - September 2009 and June 2010. The materials are; map of area, list of names, questionnaires, voices recorder, note book, and digital camera. The sampling method was snowball sampling which resulted in the qualitative and quantitative data taken. For qualitative data, ethnography and life history was used. For quantitative, a statistical survey with a semi-structured questionnaire was used. 50 respondents per each site participated voluntarily. Data was analyzed by performing MAXQDA 10, and F4 audio analysis software (created and developed by Philip-University Marburg). The data is clustered based on causality. The results show that; the role of IK on TFS (traditional farming system) shown on NPLM which has higher food crop biodiversity in comparison to the other three places even though it has relatively similar temperature and rainfall. This high food crop biodiversity is due to the awareness of local people who realized that they lived in unfavourable climate and topography; therefore they are more prepared for any changes that may occur. Carbohydrate intake is 100 % through rice even though they are growing different staple crops. Whereas most of the people said in the interviews that not eating rice is like not really eating for them. In addition to that, mothers still play an important role in kitchen activities. But when the agriculture income is low, mothers have to decide whether to change the meals or to feel insecure about their food supply. Marantau yields positive impact through the remittances it provides to invest on the farm. On the other hand, it results in fewer workers for agriculture, and therefore a negative impact on the transfer of IK. The investigation showed that the local government has a PTS (Padi Tanam Sabatang) programme which still does not guarantee that the farmers are getting sufficient revenue from their land. The low agricultural income leads to situation of potential food insecurity. It is evident that education is equal among men and women, but in some cases women tend to leave school earlier because of arranged marriages or the distances of school from their homes. Men predominantly work in agriculture and fishing, while women work in the kitchen. In NAB, even though women work on farmland they earn less then men. Weaving (NPS) and kitchen activity is recognized as women’s work, which also supports the household income. Mass media is not yielding any changes in TFS and food culture in these days. The traditional farming system has changed because of intensive agricultural extension which has introduced new methods of agriculture for the last three decades (since the 1980’s). There is no evidence that they want to change any of their food habits because of the mass media despite the lapau activity which allows them to get more food choices, instead preparing traditional meal at home. The recommendations of this thesis are: 1) The empowerment of farmers. It is regarding the self sufficient supply of manure, cooperative seed, and sustainable farm management. Farmers should know – where are they in their state of knowledge – so they can use their local wisdom and still collaborate with new sources of knowledge. Farmers should learn the prognosis of supply and demand next prior to harvest. There is a need for farm management guidelines; that can be adopted from both their local wisdom and modern knowledge. 2) Increase of non-agricultural income Increasing the non-agricultural income is strongly recommended. The remittances can be invested on non-agricultural jobs. 3) The empowerment of the mother. The mother plays an important role in farm to fork activities; the mother can be an initiator and promoter of cultivating spices in the backyard. Improvement of nutritional knowledge through information and informal public education can be done through arisan ibu-ibu and lapau activity. The challenges to apply these recommendations are: 1) The gap between institutions and organizations of local governments. There is more than one institution involved in food security policy. 2) Training and facilities for field extension agriculture (FEA) is needed because the rapid change of interaction between local government and farmer’s dependent on this agency.

On the regulation of spatial externalities: coexistence between GM and conventional crops in the EU and the 'newcomer principle'

Pollen-mediated gene flow is one of the main concerns associated with the introduction of genetically modified (GM) crops. Should a premium for non-GM varieties emerge on the market, ‘contamination’ by GM pollen would generate a revenue loss for growers of non-GM varieties. This paper analyses the problem of pollen-mediated gene flow as a particular type of production externality. The model, although simple, provides useful insights into coexistence policies. Following on from this and taking GM herbicide-tolerant oilseed rape (Brassica napus) as a model crop, a Monte Carlo simulation is used to generate data and then estimate the effect of several important policy variables (including width of buffer zones and spatial aggregation) on the magnitude of the externality associated with pollen-mediated gene flow.

Testing the principle of equivalence by supernova neutrinos

We study the possible impact of the neutrino oscillation which could be induced by a tiny violation of equivalence principle (VEP) on the observation of neutrinos emitted from supernova driven by gravitational collapse. We show that using supernova neutrinos, one can probe very small values of VEP parameters, delta(tau) less than or similar to O(10(-31)) for massless or degenerated neutrinos and delta(tau) less than or similar to O(10(-16)) x (Deltam(2)/10(-5) eV(2)) for massive neutrinos. (C) 2002 Elsevier B.V. B.V. All rights reserved.

A scale variational principle of Herglotz

The Herglotz problem is a generalization of the fundamental problem of the calculus of variations. In this paper, we consider a class of non-differentiable functions, where the dynamics is described by a scale derivative. Necessary conditions are derived to determine the optimal solution for the problem. Some other problems are considered, like transversality conditions, the multi-dimensional case, higher-order derivatives and for several independent variables.

Pedagogia do esporte : organização, sistematização, aplicação e avaliação de conteúdos esportivos na educação não formal = Sport pedagogy : organization, systematization and application of sports content in non-formal education

Universidade Estadual de Campinas . Faculdade de Educação Física

Breastfeeding and non-nutritive sucking patterns related to the prevalence of anterior open bite in primary dentition

OBJECTIVE: Nutritional, immunological and psychological benefts of exclusive breastfeeding for the frst 6 months of life are unequivocally recognized. However, mothers should also be aware of the importance of breastfeeding for promoting adequate oral development. This study evaluated the association between breastfeeding and non-nutritive sucking patterns and the prevalence of anterior open bite in primary dentition. MATERIAL AND METHODS: Infant feeding and non-nutritive sucking were investigated in a 3-6 year-old sample of 1,377 children, from São Paulo city, Brazil. Children were grouped according to breastfeeding duration: G1 - non-breastfed, G2 - shorter than 6 months, G3 - interruption between 6 and 12 months, and G4 - longer than 12 months. Three calibrated dentists performed clinical examinations and classifed overbite into 3 categories: normal, anterior open bite and deep bite. Chi-square tests (p<0.05) with odds ratio (OR) calculation were used for intergroup comparisons. The impact of breastfeeding and non-nutritive sucking on the prevalence of anterior open bite was analyzed using binary logistic regression. RESULTS: The prevalence estimates of anterior open bite were: 31.9% (G1), 26.1% (G2), 22.1% (G3), and 6.2% (G4). G1 would have signifcantly more chances of having anterior open bite compared with G4; in the total sample (OR=7.1) and in the subgroup without history of non-nutritive sucking (OR=9.3). Prolonging breastfeeding for 12 months was associated with a 3.7 times lower chance of having anterior open bite. In each year of persistence with non-nutritive sucking habits, the chance of developing this malocclusion increased in 2.38 times. CONCLUSIONS: Breastfeeding and non-nutritive sucking durations demonstrated opposite effects on the prediction of anterior open bite. Non-breastfed children presented signifcantly greater chances of having anterior open bite compared with those who were breastfed for periods longer than 12 months, demonstrating the benefcial infuence of breastfeeding on dental occlusion.

Cosmic distance duality relation and the shape of galaxy clusters

Context. Observations in the cosmological domain are heavily dependent on the validity of the cosmic distance-duality (DD) relation, eta = D(L)(z)(1+ z)(2)/D(A)(z) = 1, an exact result required by the Etherington reciprocity theorem where D(L)(z) and D(A)(z) are, respectively, the luminosity and angular diameter distances. In the limit of very small redshifts D(A)(z) = D(L)(z) and this ratio is trivially satisfied. Measurements of Sunyaev-Zeldovich effect (SZE) and X-rays combined with the DD relation have been used to determine D(A)(z) from galaxy clusters. This combination offers the possibility of testing the validity of the DD relation, as well as determining which physical processes occur in galaxy clusters via their shapes. Aims. We use WMAP (7 years) results by fixing the conventional Lambda CDM model to verify the consistence between the validity of DD relation and different assumptions about galaxy cluster geometries usually adopted in the literature. Methods. We assume that. is a function of the redshift parametrized by two different relations: eta(z) = 1+eta(0)z, and eta(z) = 1+eta(0)z/(1+z), where eta(0) is a constant parameter quantifying the possible departure from the strict validity of the DD relation. In order to determine the probability density function (PDF) of eta(0), we consider the angular diameter distances from galaxy clusters recently studied by two different groups by assuming elliptical (isothermal) and spherical (non-isothermal) beta models. The strict validity of the DD relation will occur only if the maximum value of eta(0) PDF is centered on eta(0) = 0. Results. It was found that the elliptical beta model is in good agreement with the data, showing no violation of the DD relation (PDF peaked close to eta(0) = 0 at 1 sigma), while the spherical (non-isothermal) one is only marginally compatible at 3 sigma. Conclusions. The present results derived by combining the SZE and X-ray surface brightness data from galaxy clusters with the latest WMAP results (7-years) favors the elliptical geometry for galaxy clusters. It is remarkable that a local property like the geometry of galaxy clusters might be constrained by a global argument provided by the cosmic DD relation.

NMR analog of Bell's inequalities violation test

In this paper, we present an analog of Bell's inequalities violation test for N qubits to be performed in a nuclear magnetic resonance (NMR) quantum computer. This can be used to simulate or predict the results for different Bell's inequality tests, with distinct configurations and a larger number of qubits. To demonstrate our scheme, we implemented a simulation of the violation of the Clauser, Horne, Shimony and Holt (CHSH) inequality using a two-qubit NMR system and compared the results to those of a photon experiment. The experimental results are well described by the quantum mechanics theory and a local realistic hidden variables model (LRHVM) that was specifically developed for NMR. That is why we refer to this experiment as a simulation of Bell's inequality violation. Our result shows explicitly how the two theories can be compatible with each other due to the detection loophole. In the last part of this work, we discuss the possibility of testing some fundamental features of quantum mechanics using NMR with highly polarized spins, where a strong discrepancy between quantum mechanics and hidden variables models can be expected.

Non-Cardiac Surgery in Developing Countries: Epidemiological Aspects and Economical Opportunities - The Case of Brazil

Background: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. Methods and Findings: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than $1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near $98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). Conclusion: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.

NON-NEWTONIAN FLOW AND PRESSURE DROP OF PINEAPPLE JUICE IN A PLATE HEAT EXCHANGER

The study of non-Newtonian flow in plate heat exchangers (PHEs) is of great importance for the food industry. The objective of this work was to study the pressure drop of pineapple juice in a PHE with 50 degrees chevron plates. Density and flow properties of pineapple juice were determined and correlated with temperature (17.4 <= T <= 85.8 degrees C) and soluble solids content (11.0 <= X(s) <= 52.4 degrees Brix). The Ostwald-de Waele (power law) model described well the rheological behavior. The friction factor for non-isothermal flow of pineapple juice in the PHE was obtained for diagonal and parallel/side flow. Experimental results were well correlated with the generalized Reynolds number (20 <= Re(g) <= 1230) and were compared with predictions from equations from the literature. The mean absolute error for pressure drop prediction was 4% for the diagonal plate and 10% for the parallel plate.

Bioactive compounds and antioxidant capacities of 18 non-traditional tropical fruits from Brazil

The bioactive compounds and antioxidant capacities of polyphenolic extracts of 18 fresh and dry native non-traditional fruits from Brazil were determined using ABTS, DDPH, FRAP and beta-carotene bleaching methods. The study provides an adaptation of these methods, along with an evaluation of the compounds related to antioxidant potential. The results show promising perspectives for the exploitation of non-traditional tropical fruit species with considerable levels of nutrients and antioxidant capacity. Although evaluation methods and results reported have not yet been sufficiently standardised, making comparisons difficult, our data add valuable information to current knowledge of the nutritional properties of tropical fruits, such as the considerable antioxidant capacity found for acerola - Malpighia emarginata and camu-camu - Myrciaria dubia (ABTS, DPPH and FRAP) and for puca-preto - Mouriri pusa (all methods). (C) 2010 Elsevier Ltd. All rights reserved.

Sudden onset of log-periodicity and superdiffusion in non-Markovian random walks with amnestically induced persistence: exact results

Random walks can undergo transitions from normal diffusion to anomalous diffusion as some relevant parameter varies, for instance the L,vy index in L,vy flights. Here we derive the Fokker-Planck equation for a two-parameter family of non-Markovian random walks with amnestically induced persistence. We investigate two distinct transitions: one order parameter quantifies log-periodicity and discrete scale invariance in the first moment of the propagator, whereas the second order parameter, known as the Hurst exponent, describes the growth of the second moment. We report numerical and analytical results for six critical exponents, which together completely characterize the properties of the transitions. We find that the critical exponents related to the diffusion-superdiffusion transition are identical in the positive feedback and negative feedback branches of the critical line, even though the former leads to classical superdiffusion whereas the latter gives rise to log-periodic superdiffusion.

Inhibition of settlement and metamorphosis of the ascidian Herdmania curvata by non-geniculate coralline algae

The surfaces of non-geniculate coralline algae (NCA) are known to induce the settlement and metamorphosis of disparate marine taxa. In this study we investigate the responsiveness of larvae of Herdmania curvata (Ascidiacea: Stolidobranchia) to three species of NCA (Neo-goniolithon brassica-florida, Hydrolithon onkodes, and Lithothamnium prolifer) that cohabit the slope and crest of Heron Reef, Great Barrier Reef. H. curvata larvae were first exposed to these NCA at or within 2 h of hatching, which is 1 to 2 h prior to attaining competence, and then cultured continuously with the NCA for 12 to 14 h. Rates of settlement and metamorphosis of H, curvata cultured in laboratory chambers in the presence of the different NCA were significantly lower than spontaneous rates in seawater. The limited settlement in treatments containing NCA were confined entirely to the chamber periphery, and settlement never occurred on the surface of the NCA. The inhibitory effect was dose-dependent and was stronger in H. brassica-florida and H. onkodes than in L. prolifer. Larvae that did not settle in treatments with NCA had rounded anterior trunks and, in extreme cases, kinked tails with rounded and dissociated tail muscle cells. In some individuals, we observed the anterior chemosensory papillae being sloughed off the larval body. Morphological analysis of trunk ectodermal and mesenchymal nuclei of larvae cultured in the presence of the NCA revealed that general necrotic cell death was occurring. Importantly, H. curvata larvae that were exposed to NCA could not subsequently be induced to metamorphose in KCl-elevated seawater, whereas larvae not exposed to NCA metamorphosed at high rates in KCl-elevated seawater.