Prevalence and clinical outcomes for patients with MET protein expression in patients with non-small cell lung cancer in Europe: Results from the European Thoracic Oncology Platform Lungscape Project.

Aim The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR. Methods Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity. Results A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p < 0.001), with performance status (25% vs. 18% for 0 vs. 1-3, p = 0.006), and histology (34%, 14% and 24% for adenocarcinoma, squamous and large cell carcinoma, p < 0.001). IHC MET positivity was independent of the IHC ALK status (p = 0.08). At last FU, 52% of patients were still alive, with a median FU of 4.8 yrs. No association of IHC MET was found with OS, RFS or TTR. Conclusions The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented. Disclosure L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.

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.

Sickness certification in primary care: a survey on views and practices among Swiss physicians.

QUESTIONS UNDER STUDY: Studies from several countries (Scandinavia, United Kingdom) report that general practitioners (GPs) experience problems in sickness certification. Our study explored views of Swiss GPs towards sickness certification, their practice and experience, professional skills and problematic interactions with patients. METHODS: We conducted an online survey among GPs throughout Switzerland, exploring behaviour of physicians, patients and employers with regard to sickness certification; GPs' views about sickness certification; required competences for certifying sickness absence, and approaches to advance their competence. We piloted the questionnaire and disseminated it through the networks of the five Swiss academic institutes for primary care. RESULTS: We received 507 valid responses (response rate 50%). Only 43/507 GPs experienced sickness certification as problematic per se, yet 155/507 experienced problems in sickness certification at least once a week. The 507 GPs identified estimating a long-term prognosis about work capacity (64%), handling conflicts with patients (54%), and determining the reduction of work capacity (42%) as problematic. Over 75% would welcome special training opportunities, e.g., on sickness certifications during residency (93%), in insurance medicine (81%), and conflict management (80%). CONCLUSION: Sickness certification as such does not present a major problem to Swiss GPs, which contrasts with the experience in Scandinavian countries and in the UK. Swiss GPs did identify specific tasks of sickness certification as problematic. Training opportunities on sick-leave certification and insurance medicine in general were welcomed.

Pediatric advance care planning from the perspective of health care professionals: a qualitative interview study.

BACKGROUND: Pediatric advance care planning differs from the adult setting in several aspects, including patients' diagnoses, minor age, and questionable capacity to consent. So far, research has largely neglected the professionals' perspective. AIM: We aimed to investigate the attitudes and needs of health care professionals with regard to pediatric advance care planning. DESIGN: This is a qualitative interview study with experts in pediatric end-of-life care. A qualitative content analysis was performed. SETTING/PARTICIPANTS: We conducted 17 semi-structured interviews with health care professionals caring for severely ill children/adolescents, from different professions, care settings, and institutions. RESULTS: Perceived problems with pediatric advance care planning relate to professionals' discomfort and uncertainty regarding end-of-life decisions and advance directives. Conflicts may arise between physicians and non-medical care providers because both avoid taking responsibility for treatment limitations according to a minor's advance directive. Nevertheless, pediatric advance care planning is perceived as helpful by providing an action plan for everyone and ensuring that patient/parent wishes are respected. Important requirements for pediatric advance care planning were identified as follows: repeated discussions and shared decision-making with the family, a qualified facilitator who ensures continuity throughout the whole process, multi-professional conferences, as well as professional education on advance care planning. CONCLUSION: Despite a perceived need for pediatric advance care planning, several barriers to its implementation were identified. The results remain to be verified in a larger cohort of health care professionals. Future research should focus on developing and testing strategies for overcoming the existing barriers.

Interdependency management in universities: a case study

There remains uncertainty in scientific discussions regarding the governance of universities in new public management regimes in terms of who actually 'rules' in the university. Apparently, a strengthened management leadership is confronted with continuing elements of academic self-regulation and professional autonomy in knowledge production and diffusion. Organisational and academic rationales coexist in today's management of universities. This article endeavours to clarify some of the ambiguities pertaining to the coexistence of two authorities by demonstrating the working of 'interdependency management' that is taking place within universities. For this purpose, the authors have scrutinised research, teaching and recruitment policies in one Swiss university that is subject to such ambiguities. The study confirms existing research in that a command-and-control system is not applied. Policymaking in universities is instead based on a mix of negotiations in faculties that are taking place in the 'shadow of hierarchy', negotiated bargaining between faculties and leaders and occasional unilateral decisions of leaders. This mitigates latent conflicts between management and the academic community: strategic orientations of the university are generally accepted by the academic community while the academic community has influence on policy formulation and maintains defining powers over policy substance.

Gli altri noi : Rom e residenti nella Svizzera italiana : etnografia e mediazione

Cette recherche porte sur les roms (vlach) qui séjournent périodiquement en Suisse italienne, en camping-cars ou en caravanes, pratiquant un semi- nomadisme lié à des motivations principalement économiques, mais également familiales et religieuses. Elle poursuit simultanément deux objectifs. Le premier est lié à un souci de médiation culturelle, qui rejoint les réflexions sur la façon de gérer au mieux les conflits entre les diverses composantes du vivre ensemble. Le second vise à approfondir la connaissance des populations roms concernées (lovara, éurara ou kalderasa, de nationalités italienne, française et espagnole). Les deux objectifs sont évidemment reliés, car comprendre les dynamiques conflictuelles exige la connaissance approfondie des acteurs en interaction. Les relations entre résidents tessinois et roms ont évolué dans le temps, avec des oscillations entre le pôle du refus et celui de l'attraction, entre rejet et reconnaissance, méfiance et confiance. Ces variations historiques renvoient à un fondement commun, à une dynamique des oppositions réciproques. L'analyse anthropologique a fait apparaître le rôle ambivalent du conflit dans la production et la reproduction de la relation d'altérité. L'exclusion des roms fournit à certaines tendances politiques locales l'occasion d'apparaître comme les protecteurs des résidents contre les étrangers ; inversement, l'opposition des roms aux gaiés leur permet de resserrer leur communauté et de prévenir l'assimilation. La médiation culturelle peut espérer gérer cette dynamique relationnelle, certainement pas la faire disparaître. Le modèle intégratif traditionnel de l'État- nation se révèle trop étroit pour accueillir la culture rom. Casser la résistance des roms envers le travail salarié et envers la scolarisation obligatoire, entraver leur semi-nomadisme (qui incite aussi leurs rencontres familiales et religieuses), refuser de reconnaître leur organe de justice interne et leur langue, tout cela ne ferait que concourir à leur disparition culturelle. Les roms sont conscients de ces possibilités, raison pour laquelle ils maintiennent une ambivalence relationnelle avec les ga£és, quitte à apparaître comme des « tsiganes indésirables ». Abstract : This research focuses on the Roma people (Vlach) who periodically stay in Italian Switzerland in caravans or camper vans, practising a semi-nomadic lifestyle - a choice based mainly on economic imperatives but also on familial and religious grounds. This study will address two objectives at the same time. The first involves cultural mediation, and considers the best way to manage the existing conflicts between the cultural components of the social environment. The second aims to increase knowledge of the Roma populations under examination - the Italian, French and Spanish Lovara, Éurara or Kalderasa. The two objectives are clearly linked, as a deeper understanding of the people involved is vital if we are to increase understanding of the dynamics of confrontation. The relationships between the residents of the Ticino area and the Roma people have evolved over time, oscillating in varying degrees between rejection and attraction, confrontation and recognition, suspicion and trust. These variations spring from a common base, a dynamic shaped by mutual opposition. The anthropological analysis highlights the ambivalent role of conflict in the production and reproduction of relations of otherness. Excluding the Roma has given some local politicians the opportunity to position themselves as protectors of residents against foreigners. Inversely, the Roma people's opposition to the Gazé strengthens links within their community and prevents assimilation. Cultural mediation may aspire to manage this relational dynamic, but not abolish it. The traditional integrative model of the nation-state has shown itself to be too restrictive to accommodate the Romani culture. Rejecting the Roma's resistance to salaried work and obligatory schooling, obstructing their semi-nomadic lifestyle (one that also involves family and religious assemblies) and refusing to recognise their traditional courts and mother tongue, all that can only contribute to the dilution of their cultural heritage. The Roma are fully aware of these possibilities, which is why they retain a relational ambivalence in their dealings with the Gazé, at the cost of appearing to be "undesirable gypsies".

World Polarization in carbon emissions, potential conflict and groups: an updated revision

Typically, conflicts in world environmental negotiations are related, amongst other aspects, to the level of polarization of the countries in groups with conflicting interests. Given the predictable relationship between polarization and conflict, it would seem logical to evaluate the degree to which the distribution of countries – for example, in terms of their CO2 emissions per capita – would be structured through groups which in themselves are antagonistic, as well as their evolution over time. This paper takes the concept of polarization to explore this distribution for the period 1992-2010, looking at different analytic approaches related to the concept. Specifically, it makes a comparative evaluation of the results associated with endogenous multi-polarization measures (i.e. EGR and DER indices), exogenous measures (i.e. Z-K or multidimensional index) and strict bipolarization measures (i.e. Wolfson’s measure). Indeed, the interest lies not only in evaluating the global situation of polarization by comparing the different approaches and their temporal patterns, but also in examining the explanatory capacity of the different proxy groups used as a possible reference for designing global environmental policy from a group premise. JEL codes: D39; Q43; Q56. Key words: polarization; carbon emissions; conflict;

Phylogenomics Controlling for Base Compositional Bias Reveals a Single Origin of Eusociality in Corbiculate Bees.

As increasingly large molecular data sets are collected for phylogenomics, the conflicting phylogenetic signal among gene trees poses challenges to resolve some difficult nodes of the Tree of Life. Among these nodes, the phylogenetic position of the honey bees (Apini) within the corbiculate bee group remains controversial, despite its considerable importance for understanding the emergence and maintenance of eusociality. Here, we show that this controversy stems in part from pervasive phylogenetic conflicts among GC-rich gene trees. GC-rich genes typically have a high nucleotidic heterogeneity among species, which can induce topological conflicts among gene trees. When retaining only the most GC-homogeneous genes or using a nonhomogeneous model of sequence evolution, our analyses reveal a monophyletic group of the three lineages with a eusocial lifestyle (honey bees, bumble bees, and stingless bees). These phylogenetic relationships strongly suggest a single origin of eusociality in the corbiculate bees, with no reversal to solitary living in this group. To accurately reconstruct other important evolutionary steps across the Tree of Life, we suggest removing GC-rich and GC-heterogeneous genes from large phylogenomic data sets. Interpreted as a consequence of genome-wide variations in recombination rates, this GC effect can affect all taxa featuring GC-biased gene conversion, which is common in eukaryotes.

Campesinos, Estado y mercado. La conflictividad forestal en el Noroeste de España, León (1870­ ¿1936)

Peer-reviewed

Individual Perception of Organizational Values

The objective of this master’s thesis was to examine how corporate values come true among the white-collar employees in the case organization. It was also studied if values were perceived similarly in the different departments. Impact of organizational position and education on value orientation was tested through hypotheses based on earlier values research. There are only few value scales available for measuring organizational values. The empirical study results indicate that personnel’s perception of organizational values can be measured statistically. When defining the scale it is utmost important to link the questions and claims close to the employees’ daily working environment. In this study, Work ethic appeared as the strongest organizational value reflecting respondents’ commitment to their duties. Related to corporate values, Performance was perceived as the strongest value and Emphasis on people the weakest. Value consensus between the departments varied. According to the previous research organizational position and educational level has an impact on value perceptions. In this study, employees in superior position or with higher education perceived organizational values to come true better than subordinates or employees with lower education. Empirical data (N=229) was collected by a web-based survey questionnaire among white-collar employees in the case organization in April 2008. Statistical analyses were performed by SPSS programme.

Osake- ja henkilöyhtiöiden sulautuminen vero-oikeudessa, yhtiöoikeudessa ja kirjanpidossa

Sulautuminen on yksi yleisimmistä yritysjärjestelyvaihtoehdoista. Sulautumisessa on otettava huomioon vero- ja yhtiöoikeudelliset sekä kirjanpidolliset seikat. Ne ohjaavat sulautumisen toteuttamista ja säätelevät sallittuja menettelytapoja. Tutkimuksen päätavoitteena on analysoida osakeyhtiön, avoimen ja kommandiittiyhtiön vero-oikeudellisen, yhtiöoikeudellisen ja kirjanpidollisen sulautumisen käsittelyn eroja. Tutkimuksessa on aluksi selvitetty syitä yritysjärjestelyihin ja sulautumista yritysjärjestelyvaihtoehtona. Sulautumisen käsittely aloitetaan osakeyhtiön sulautumisen yhtiöoikeudellisen sääntelyn käsittelemisellä. Seuraavaksi tutkittiin kirjanpidollista sääntelyä sulautumisen yhteydessä. Tämän jälkeen määritettiin verotuksen sääntelyä sulautumisen yhteydessä. Viimeisessä teoriakappaleessa käsitellään henkilöyhtiöiden sulautumista. Tutkimuksessa selvitettiin sulautumisen oikeudellinen sääntely ja havaittiin säännöksissä olevan ristiriitaisuuksia, jotka vaikuttavat sulautumisessa tehtäviin päätöksiin.

Afrontamiento de situaciones de hostilidad y desempeño de la función directiva. Planteamientos y reflexiones a raíz de una actividad de formación permanente de directivos de centros educativos de titularidad pública

The intervention in the organized conflicts and, particularly, the confrontation of hostile situations (based on the emotional alteration, the strain, the verbal aggressiveness, etc) is one of the aspects that worry the principals of the educative centres and, therefore, a main attention must be given to the initial and permanent training to have managing duties. Throughout the text we take some aspects into account in the development of these managing skills:a) we set the distinctive features; b) we answer to the dilemma about the existence of improvement possibilities; c) we state the need to star from the motivation and the active participation of the principals in their own personal development and, finally, d) we contribute with the design of a training activity to develop skills to confront hostile situations, addressed to the principals of primary and secondary schools, that was done in Girona, in November 2005

Exits - Pääomasijoittajan irtautumisvaihtoehtojen juridista tarkastelua

Pääomasijoittaminen on Suomessa verrattain uusi ilmiö. Tutkielman tarkoitus on ollut tarkastella pääomasijoittajan irtautumista kohdeyhtiöstä juridisesta näkökulmasta. Tutkielman ydin on ollut selvittää pääomasijoittamisen toimijoiden roolien ja niistä johtuvien intressien ristiriitojen vaikutusta irtautumiseen sekä sitä, miten intressiristiriitoja vähennetään erityisesti pääomasijoittajan näkökulmasta. Teoreettisena viitekehyksenä on käytetty päämies-agenttiteoriaa sekä teoriaa asymmetrisestä tiedosta ja moraalisesta uhkapelistä. Toisena tutkimusongelmana on selvitetty pääomasijoittamisen sijoittumista eri oikeudenalojen yhtymäkohtaan sekä luotu katsaus yleisesti pääomasijoittamista koskevaan lainsäädäntöön. Keskeisenä tavoitteena on ollut selvittää, aiheuttaako amerikkalaiseen sopimusmalliin perustuva sopimuskäytäntö ongelmia suomalaisessa juridisessa ympäristössä. Tutkimus on oikeustaloustieteellinen ja tutkimuskohteeseen on tutustuttu alan koti- ja ulkomaisen tutkimuksen ja kirjallisuuden lisäksi teemahaastatteluin. Tutkielman loppupäätelmä on, että pääomasijoittajan irtautumisen turvaamiseksi käytetään juridisesti tehokkaita menetelmiä, joista osakassopimuksen ehdot ovat ennemminkin ennaltaehkäiseviä kuin korjaavia. Intressiristiriitaa vähentämään käytetään myös kannustinjärjestelmä (osakeomistusta, optio-oikeuksia). Tutkimuksessa ei havaittu merkittäviä ongelmia amerikkalaisen sopimusmallin soveltamisessa suomalaiseen käytäntöön.

Recerca avaluativa sobre el programa “LÍMITS”

Des de la comunitat científica s’ha posat de manifest la necessitat d’avaluar els programes d’intervenció per a la millora de la parentalitat, especialment en el context de la infància i adolescència en risc. En aquesta recerca es presenten els resultats de l’avaluació del programa Límits aportant evidències d’eficàcia i efectivitat, que permeten identificar i descriure les seves fortaleses, així com també aquells elements que poden ser objecte de millora. El programa Límits és una proposta estructurada d’intervenció preventiva de caire selectiu amb grups de famílies de joves d’entre 14 i 18 anys que passen pel circuit de la justícia juvenil. El programa ha estat funcionant des del 2007, en diverses edicions, a tot el territori català aplegant una experiència i trajectòria remarcable que ha incidit en 351 persones i 245 famílies. El programa consta de vuit sessions en grup d’entre dotze i quinze participants, dinamitzat per dos monitors, en les que es treballen diferents estratègies a partir de l’abordatge de continguts relacionats amb les relacions i els lligams, la comunicació, els conflictes, l’establiment de normes i la disciplina. Per dur a terme l’avaluació del programa Límits s’ha partit d’un disseny quasi-experimental, pretest–postest aplicat a un grup programa (GP) i a grup col·laborador (GC) i de manera diferida (dos mesos després de la seva finalització) només al GP per constatar si s’han assolit els resultats previstos. Quan s’analitza l’evolució del GP s’observen millores en les habilitats d’autocontrol de les emocions, el reforç positiu i les relacions familiars. Tanmateix, des del punt de vista de les famílies no s’han observat canvis significatius en la millora de la percepció d’auto eficàcia del rol parental respecte el GC abans i després del programa. La percepció majoritària és que els objectius que planteja el programa són excessivament ambiciosos i en conseqüència, difícilment assolibles. Els responsables consideren que, en alguns casos, el perfil de famílies derivades al programa no és el més adequat perquè presenten problemàtiques molt més agudes a les desitjables per aquest tipus d’intervenció. Com a punts forts, es destaca que el programa és útil als ulls dels responsables i tècnics perquè genera una presa de consciència del problema i de la necessitat de canvi per part de les famílies. Els participants diuen transferir a la vida real algunes habilitats apreses especialment la comunicació i millora de les relacions familiars. Els tècnics aplicadors coincideixen amb la percepció de les famílies tot i declarar percentatges lleugerament inferiors. També és vist com un complement professional a la seva tasca que ajuda a fer un millor seguiment dels casos, i permet seguir treballant amb posterioritat amb les famílies.