Non-small cell lung cancer: the prevalence of oncogenic driver mutations in Switzerland

Background. Predictive molecular marker analyses are standard of care in order to select non-small cell lung cancer (NSCLC) patients for targeted therapies. The aim of this study was to determine the prevalence of targetable oncogenic driver mutations including EGFR, KRAS, BRAF, HER2, ALK and ROS1 in Switzerland. Methods. Eight Swiss pathology institutions provided retrospective and anonymized data on their predictive molecular marker results performed on NSCLC from January 2012 to December 2014. Clinico-pathological data were recorded including age, gender, histological NSCLC-subtype and specimen type (biopsy, conventional cytology and cell block, respectively) used for molecular analyses. The prevalence of oncogenic mutations were calculated and compared between the centres. Results. A total of 4187 NSCLC were included into the study. The median age was 67 years and 55% were male patients. The tumor specimens for molecular analysis were mostly derived from biopsies (69%), 26% were from conventional cytology specimens and only in 5% from cell blocks. The most prevalent gene mutation was KRAS with 30.6% (range: 27.3-33.9%), followed by EGFR, BRAF and HER2 mutations in 12.2% (range: 10.2-13.1%), 3.9% (range: 2.5-5.6%) and 1.1% (range: 0.9-4.0%), respectively, without significant differences between the eight centers. Concomitant EGFR and KRAS mutations were detected in only 3/2027 NSCLC. In contrast the prevalence of ALK (mean 6.5%, range: 2.8-11.7%) and ROS1 (mean 2.4%, range: 1.5-6.2%) rearrangements varied significantly between centers. Conclusions. The Prevalence of EGFR, KRAS, BRAF and HER2 mutations are well in line with data from other West European populations. Concomitant EGFR, KRAS, BRAF or HER2 mutations are exceptional. ALK FISH results vary significantly between the eight centres. Concomitant ALK FISH positive results in NSCLC harbouring other oncogenic driver mutation have only been observed in two smaller centres, highlighting the difficulty in ALK-FISH interpretation.

Introgressive hybridization of threatened European tree frogs (Hyla arborea) by introduced H. intermedia in Western Switzerland

Hybridization by introduced taxa is a major threat to native species. Characterizing human introductions is thus one of the missions of conservation geneticists. Here we survey a declining population of the regionally endangered European tree frog (Hyla arborea) in the Grangettes natural reserve (Rhone valley, Western Switzerland), where previous evidence indicated human introduction of the Italian taxon H. intermedia. We combined fast-evolving mitochondrial and nuclear markers and an extended sampling to conduct population genetic analyses of the Grangettes and putative source areas. We show that the Grangettes population is a hybrid swarm, with all individuals featuring recent nuclear admixture and mitochondrial DNA of introduced H. intermedia, most likely of proximate south Alpine origin. In contrast, H. arborea and H. intermedia hardly introgress in their natural parapatric ranges, consistent with an advanced reproductive isolation. Thus, potential hybrid incompatibilities may account for the strong decline of this population, despite important conservation efforts. Although their hybrid nature makes them a priori unworthy of any protection, we propose specific measures to recover local H. arborea gene pool and preserve tree frogs in the Grangettes, the last population remaining from this heavily impacted part of the Alps.

Switzerland as a "fractured" nation

This article deals with Swiss nationalism and Swiss nation-building. Its main thesis is that Switzerland cannot accurately be described as either a nation or a non-nation but is something in between, and could thus best be characterised as a 'fractured' nation. Switzerland has experienced some powerful nationalist moments, from the creation of the Swiss state in 1848 to the last few decades. Yet this recurrent nationalism among the Swiss, considered alongside their more traditional reluctance to consider themselves a nation, make Switzerland a peculiar object: a 'fractured' nation. This flawed process of nation-building in turn reveals some basic characteristics of all nations - inherent artificiality, and the tremendous efforts undertaken to hide it. Switzerland could be considered an unfinished, incomplete nation, and this is precisely why its study can be interesting for scholars of nations and nationalism.

Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects.

BACKGROUND: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. METHODS: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. RESULTS: Thirteen patients from 6 non-related families were included. Age of onset was 18.8 ± 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869C>T (p.Gln957Stop), c.5928G>A (p.Trp1976Stop)). CONCLUSIONS: Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2T>C) suggested a possible founder effect.

Late careers and the transition to retirement in Switzerland

A substantial body of life-course research has considered occupational trajectories in Switzerland focusing either on early or middle adulthood careers. However, the issue of the last working period and the retirement transition is receiving increasing attention for several reasons: the permanence of low birth rates associated with an ageing population, a high proportion of active old workers, continuous changes in the timing of retirements, and active ageing policies aiming at keeping people working after the state pension age. Moving forward on this topic, the present doctoral thesis aimed to offer new insights on the dynamics of the final career phase and the transition to retirement in Switzerland through a life-course approach. Concerning the main results, this thesis provides consistent evidences on the great influence of longterm familial and employment trajectories as well as individual positional factors on (i) the vulnerability during the last working period, (ii) the timing of retirement, (iii) the voluntariness of late retirement, and (iv) the financial well-being of retirees. In this way, this thesis offers significant contributions to the life-course, gender, and social policy research focused on ageing processes. -- Un ensemble considérable de recherches sur les parcours de vie a examiné les trajectoires professionnelles en Suisse, en mettant l'accent sur la carrière professionnelle des jeunes et, plus tard, à l'âge adulte. Toutefois, l'étude de la fin de la carrière professionnelle (c'est-à-dire de 50 ans jusqu'à la retraite) reçoit une attention croissante pour plusieurs raisons: la persistance du faible taux de natalité associé à une population vieillissante, la forte proportion de travailleurs âgés actifs, des évolutions continues dans le moment du départ à la retraite, et des politiques visant à maintenir les personnes âgées au travail après l'âge légal de la retraite. Pour aller de l'avant sur ce sujet, la présente thèse de doctorat vise à offrir de nouvelles perspectives sur la fin de carrière et la transition à la retraite en Suisse, en mobilisant les outils de la sociologie des parcours de vie. En ce qui concerne les principaux résultats, cette thèse fournit des preuves cohérentes sur la grande influence des trajectoires professionnelles et familiales ainsi que des facteurs positionnels sur (i) la vulnérabilité au cours de la période de travail avant la retraite, (ii) le moment de départ à la retraite, (iii) le caractère volontaire de la retraite tardive, et (iv) le bien-être financier des retraités. Ainsi, cette thèse fournit d'importantes contributions à la recherche sur les parcours de vie, sur les étu es genre, et sur les politiques sociales, focalisées sur le processus de vieillissement.

Identifying Pertinent Variables for Nonresponse Follow-Up Surveys : Lessons Learned from 4 Cases in Switzerland

All social surveys suffer from different types of errors, of which one of the most studied is non-response bias. Non-response bias is a systematic error that occurs because individuals differ in their accessibility and propensity to participate in a survey according to their own characteristics as well as those from the survey itself. The extent of the problem heavily depends on the correlation between response mechanisms and key survey variables. However, non-response bias is difficult to measure or to correct for due to the lack of relevant data about the whole target population or sample. In this paper, non-response follow-up surveys are considered as a possible source of information about non-respondents. Non-response follow-ups, however, suffer from two methodological issues: they themselves operate through a response mechanism that can cause potential non-response bias, and they pose a problem of comparability of measure, mostly because the survey design differs between main survey and non-response follow-up. In order to detect possible bias, the survey variables included in non-response surveys have to be related to the mechanism of participation, but not be sensitive to measurement effects due to the different designs. Based on accumulated experience of four similar non-response follow-ups, we studied the survey variables that fulfill these conditions. We differentiated socio-demographic variables that are measurement-invariant but have a lower correlation with non-response and variables that measure attitudes, such as trust, social participation, or integration in the public sphere, which are more sensitive to measurement effects but potentially more appropriate to account for the non-response mechanism. Our results show that education level, work status, and living alone, as well as political interest, satisfaction with democracy, and trust in institutions are pertinent variables to include in non-response follow-ups of general social surveys. - See more at: https://ojs.ub.uni-konstanz.de/srm/article/view/6138#sthash.u87EeaNG.dpuf

The Regulation of Foreign Banks in Switzerland (1956-1972)

The Swiss financial centre witnessed an important shift during the 1960s: the number of foreign banks and their importance in relation to the domestic banking sector significantly increased. Faced with this rapid development, Swiss bank representatives and political and monetary authorities reacted strongly. This paper investigates the evolution of the regulatory response by Swiss banking policy actors to the proliferation of foreign financial in- stitutions. In 1969, those reactions led to the adoption of a discriminatory regime, setting higher entry barriers for foreign banks than for domestic institutions. After examining possible reasons for the attractiveness of Switzerland to foreign banks, this paper will analyse the concerns and fears of the domestic banking sector and its regulators. In this regard, it appears that issues such as mere competition, preservation of the international reputation of the Swiss banks and anti-inflationary monetary policy were central to the chosen regulatory regime. Moreover, this paper shows that foreign banks were used as scapegoats in the evolution of the Swiss system of banking supervision. They were more tightly regulated, yet the general framework remained very lax.

Reasons for late presentation to HIV care in Switzerland.

INTRODUCTION: Late presentation to HIV care leads to increased morbidity and mortality. We explored risk factors and reasons for late HIV testing and presentation to care in the nationally representative Swiss HIV Cohort Study (SHCS). METHODS: Adult patients enrolled in the SHCS between July 2009 and June 2012 were included. An initial CD4 count <350 cells/µl or an AIDS-defining illness defined late presentation. Demographic and behavioural characteristics of late presenters (LPs) were compared with those of non-late presenters (NLPs). Information on self-reported, individual barriers to HIV testing and care were obtained during face-to-face interviews. RESULTS: Of 1366 patients included, 680 (49.8%) were LPs. Seventy-two percent of eligible patients took part in the survey. LPs were more likely to be female (p<0.001) or from sub-Saharan Africa (p<0.001) and less likely to be highly educated (p=0.002) or men who have sex with men (p<0.001). LPs were more likely to have their first HIV test following a doctor's suggestion (p=0.01), and NLPs in the context of a regular check-up (p=0.02) or after a specific risk situation (p<0.001). The main reasons for late HIV testing were "did not feel at risk" (72%), "did not feel ill" (65%) and "did not know the symptoms of HIV" (51%). Seventy-one percent of the participants were symptomatic during the year preceding HIV diagnosis and the majority consulted a physician for these symptoms. CONCLUSIONS: In Switzerland, late presentation to care is driven by late HIV testing due to low risk perception and lack of awareness about HIV. Tailored HIV testing strategies and enhanced provider-initiated testing are urgently needed.

Multimorbidity in primary care : protocol of a national cross-sectional study in Switzerland.

INTRODUCTION: With the ageing of the population and the general improvement of care, an increasing number of people are living with multiple chronic health conditions or 'multimorbidity'. Multimorbidity often implies multiple medical treatments. As a consequence, the risk of adverse events and the time spent by patients for their treatments increase exponentially. In many cases, treatment guidelines traditionally defined for single conditions are not easily applicable. Primary care for individuals with multimorbidity requires complex patient-centred care and good communication between the patient and the general practitioner (GP). This often includes prioritising among the different chronic conditions. METHODS AND ANALYSIS: The main objectives of this study are to describe the burden related to multimorbidity (disease-related burden and burden of treatment) in primary care and to identify the factors influencing it. Other objectives include evaluating patients' perception of treatment burden and quality of life, assessing factors influencing that perception, and investigating prioritisation in the management of multimorbidity from the perspectives of GPs and patients. For this cross-sectional study, patient enrolment will take place in GP's private practices across Switzerland. A convenient sample of 100 GPs will participate; overall, 1000 patients with at least three chronic health conditions will be enrolled. Data will be collected as paper-based questionnaires for GPs and delayed telephone interview questionnaires for patients. GPs will provide demographic and practice-related data. In addition, each GP will complete a paper-based questionnaire for each patient that they enrol. Each patient will complete a telephone interview questionnaire. ETHICS AND DISSEMINATION: This study has been approved by the research ethics committee of Canton Vaud, Switzerland (Protocol 315/14). The results of the study will be reported in international peer-reviewed journals.

Judicialisation and Direct Democracy. Switzerland's Ban on Minaret Construction

Launched by representatives from the Union démocratique du centre (UDC) with the aim of circumventing political and judicial decisions made at both local and national levels, the 2009 federal popular initiative calling for a ban on the construction of minarets rekindled the stigmatisation of Muslims living in Switzerland. Within the prevalent institutional configuration it moreover revived controversies surrounding issues such as direct democracy versus fundamental rights, or "the will of the people" versus "the power of the judges", whether national or international. "Judicialisation" is a polysemous concept. It is not understood here as the transfer to the courts of matters of political significance - in this instance the public regulation of religion - but as a process of juridification (or juridicalisation) in which court rulings were constantly anticipated in the political debate provoked by the popular initiative.