Work Experiences and Well-Being in the First Years of Professional Work in Switzerland: A Ten-Year Follow-Up Study

The ÆQUAS (a German acronym for “Work Experiences and Quality of Life in Switzerland”) study followed young workers in five occupations over their first ten years in the labor market. Participants of the study reported on working conditions and well-being at five occasions. Overall, resources at work as well as well-being, health and personal resources remained stable or increased. Concurrently, task-related stressors increased as well. This result may reflect career progress (e.g., gaining more responsibilities may be accompanied by increasing time pressure) but development in task-related stressors as well as resources may also be related to specific occupations. Several trajectories had their turning point after the first or second year of being in the labor market, which may reflect a successful professional socialization. Even though a substantial number of participants did change their occupation over these ten years (with benefits for their well-being), development over the first ten years after vocational training implies a successful transition into labor market.

The role of zinc dynamics in growth hormone secretion

Human growth hormone (GH) causes a variety of physiological and metabolic effects in humans and plays a pivotal role in postnatal growth. In somatotroph cells of the anterior pituitary, GH is stored in concentrated forms in secretory granules to be rapidly released upon GH-releasing hormone stimulation. During the process of secretory granule biogenesis, self-association of GH occurs in the compartments of the early secretory pathway (endoplasmic reticulum and Golgi complex). Since this process is greatly facilitated by the presence of zinc ions, it is of importance to understand the potential role of zinc transporters that participate in the fine-tuning of zinc homeostasis and dynamics, particularly in the early secretory pathway. Thus, the role of zinc transporters in supplying the secretory pathway with the sufficient amount of zinc required for the biogenesis of GH-containing secretory granules is essential for normal secretion. This report, illustrated by a clinical case report on transient neonatal zinc deficiency, focuses on the role of zinc in GH storage in the secretory granules and highlights the role of specific zinc transporters in the early secretory pathway.

The Function of Norms and Values in the Construction of Social Identity in Groups who experienced intergroup Conflicts

I present my explorative research about conflict and social identity. The Social Identity Approach of Henri Tajfel and John Turner is used as theoretical frame in the study. The main question is how the construction of social identity of group members is influenced by an inter-group conflict. The research project consists of two parts: 1. An empirical study conducted with qualitative research methods to investigate a today’s congregation of the Swiss reformed Church who experienced a conflict about twenty years ago. This conflict ended by the separation of a sub-group from the congregations. This group forms an independent community today. Members of both congregations where interviewed about the meaning which membership has for them and about their interpretation of the conflict. 2. An analysis of the Gospel of Matthew with questions who where developed out of the empirical study and the Social Identity Approach to better understand the separation conflict between the Matthean community and the synagogue.

The role of phospholipase D in modulating the MTOR signaling pathway in polycystic kidney disease

The mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in polycystic kidney disease (PKD). Emerging evidence suggests that phospholipase D (PLD) and its product phosphatidic acid (PA) regulate mTOR activity. In this study, we assessed in vitro the regulatory function of PLD and PA on the mTOR signaling pathway in PKD. We found that the basal level of PLD activity was elevated in PKD cells. Targeting PLD by small molecule inhibitors reduced cell proliferation and blocked mTOR signaling, whereas exogenous PA stimulated mTOR signaling and abolished the inhibitory effect of PLD on PKD cell proliferation. We also show that blocking PLD activity enhanced the sensitivity of PKD cells to rapamycin and that combining PLD inhibitors and rapamycin synergistically inhibited PKD cell proliferation. Furthermore, we demonstrate that targeting mTOR did not induce autophagy, whereas targeting PLD induced autophagosome formation. Taken together, our findings suggest that deregulated mTOR pathway activation is mediated partly by increased PLD signaling in PKD cells. Targeting PLD isoforms with pharmacological inhibitors may represent a new therapeutic strategy in PKD.

The role of nitric oxide in Listeria encephalitis of ruminants and in rats intracisternally infected with Listeria monocytogenes

Listeria monocytogenes is a Gram-positive facultative intracellular bacteria which infects a wide range of hosts. In ruminants, infection with L. monocytogenes frequently causes encephalitis, which is usually fatal in sheep and goat, while cattle often recover with antibiotic therapy. Since the role of NO in the control of Listeria is controversial, we have studied the expression of iNOS in the brains of cattle, sheep and goats which had succumbed to listeria encephalitis. iNOS was demonstrated in decreasing intensity in the M phi of microabscesses from cattle, sheep and goat. iNOS expression was accompanied by NT in the microabscesses of cattle, but was only present to a low degree in sheep and was absent in goats. This is indirect evidence for differences in the ability to produce NO in the three species. Presence of iNOS and NT were inversely correlated with the numbers of bacteria. While microabscesses of goats contained high amounts of L. monocytogenes they occurred only rarely in cattle. To corroborate our hypothesis that NO is involved in the control of listeria encephalitis a new animal model was developed. Eleven day old infant rats were infected intracisternally with a low dose of L. monocytogenes. This resulted in a transient meningoencephalitis with moderate clinical signs and low mortality. Listeria proliferated strongly in the inflammatory lesions during the first days of infection, reached a peak at day 4 and were eliminated until day 7. The presence of bacteria was closely accompanied by high numbers of iNOS-expressing M phi and the formation of NT. Administration of the iNOS inhibitor L-NIL or the radical scavenger PBN resulted in rapid death of the treated animals. However, the increase in bacterial numbers was one order of magnitude higher for animals treated with PBN compared with L-NIL administration. This shows that NO plays an important role in the control of a brain infection with Listeria, but suggests that reactive oxidants other than NO are also involved. In conclusion, our findings point to a possible involvement of the differences in the ability to express iNOS and subsequent NO production in the different clinical outcome of listeria encephalitis in cattle and small ruminants.

Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer.

Background:Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC.Methods:FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS).Results:The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC.Conclusions:FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.

The role of brand marketing in snowboarding: A comparative study of Switzerland and New Zealand

Introduction: Brands play an essential role in the organizational structure of snowboarding by sponsoring athletes, arranging events, contributing to product development and developing long-term partnerships with other key actors. However, the specialities of their role in scene sports, such as creating identities, networking and brand marketing strategies, have not been extensively researched. This study aims to provide an analysis of the function of brands within the snowboarding subculture by comparing how the sport is organized in Switzerland and New Zealand. Sociological theories of subcultures (Hitzler & Niederbacher, 2010) and social networks (Stegbauer, 2008) are used to defi ne the structures of the sport, whereas marketing and branding theories (Adjouri & Stastny, 2006) help to understand the role of the brands. Snowboarding will be defi ned as an alternative sports subculture based on characteristics such as aesthetics, adventure and new resources of performance (Schwier, 2006). Such a defi nition also begs for a novel form of analyzing its organization. Unlike more conventional structures, the organization of snowboarding allows a variety of actors to get involved in leading the sport. By portraying and encouraging differentiated identities and lifestyles, athletes provide a space for other actors to fi nd their place within the sport (Wheaton, 2005). According to Stegbauers network theory, individual actors are able to obtain high positions and defi ne their identity depending on their ties to actors and networks within the subculture (Stegbauer, 2008). For example, social capital, contacts within the sport and insider knowledge on subculture-related information enable actors to get closer to the core (Hitzler & Niederbacher, 2010). Actors who do not have close networks and allies within the subculture are less likely to engage successfully in the culture, whether as an individual or as a commercial actor (Thorpe, 2011). This study focuses on the organizational structure of snowboarding by comparing the development of the sport in Switzerland and New Zealand. An analysis of snowboarding in two nations with diverse cultures and economic systems allows a further defi nition of the structural organization of the sport and explains how brands play an important role in the sport. Methods: The structural organization of the sport will be analyzed through an ethnographic approach, using participant observation at various leading events in Switzerland (Freestyle.ch, European Open) and New Zealand (World Heli Challenge, New Zealand Open, New Zealand Winter Games). The data is analyzed using grounded theory (Glaser & Strauss 1967) and gives an overview of the actors that are playing an important role in the local development of snowboarding. Participant observation was also used as a tool to get inside the sport culture and opened up the possibility to make over 40 semi-structured qualitative expert interviews with international core actors from 11 countries. Obtaining access to one actor as a partner early on helped to get inside the local sport culture. The ‘snowball effect’ allowed the researcher to acquire access, build trust and conduct interviews with experts within the core scene. All the interviewed actors have a direct infl uence on the sport in one or both countries, which permit a cross-analysis. The data of the interviews was evaluated through content analysis (Mayring 2010). The two methods together provided suffi cient data to analyze the organizational structure and discuss the role of brand marketing within snowboarding. Results: An actors mapping by means of a center-periphery framework has identifi ed fi ve main core groups: athletes, media representatives, brand-marketing managers, resort managers and event organizers. In both countries the same grouping of actors were found. Despite possessing different and frequently multiple roles and responsibilities, core actors appear to have a strong common identifi cation as ‘snowboarders’, are considered to be part of the organizational elite of the sport and tend to advocate similar goals. The author has found that brands in Switzerland tend to have a larger impact on the broader snowboarding culture due to a number of factors discussed below. Due to a larger amount of snowboarders and stronger economic power in Europe, snowboarders are making attempts to differentiate themselves from other winter sports, while competing with each other to develop niche markets. In New Zealand, on the other hand, the smaller market enables more cooperation and mutual respect within snowboarders. Further they are more closely linked to other winter sports and are satisfi ed with being lumped together. In both countries, brands have taken up the role of supporting young athletes, organizing competitions and feeding media with subculture-related content. Brands build their image and identity through the collaboration with particular athletes who can represent the values of the brand. Local and global communities with similar lifestyles and interests are being built around brands that share a common vision of the sport. The dominance of brands in snowboarding has enabled them with the power to organize and rule the sport through its fan base and supporters. Brands were defi ned by interviewees as independent institutions led by insiders who know the codes and symbols of the sport and were given trust and credibility. The brands identify themselves as the engines of the sport by providing the equipment, opportunities for athletes to get exposure, allowing media to get exclusive information on activities, events and sport-related stories. Differences between the two countries are more related to the economic system. While Switzerland is well integrated in the broader European market, New Zealand’s geographical isolation and close proximity to Australia tends to limit its market. Further, due to different cultural lifestyles, access to resorts and seasonal restrictions, to name a few, the amount of people practicing winter sports in New Zealand is much smaller than in Switzerland. However, this also presents numerous advantages. For example, the short southern hemisphere winter season in New Zealand enables them to attract international sports athletes, brands and representatives in a period when Europe and North America is in summer. Further, the unique snow conditions in New Zealand and majestic landscape is popular for attracting world renowned photo- and cinematographers. Another advantage is the less populated network as it provides the opportunity for individuals to gain easier access to the core of the sport, obtain diverse positions and form a unique identity and market. In Switzerland, on the other hand, the snowboarding network is dense with few positions available for the taking. Homegrown brands with core recognition are found in both countries. It was found that the Swiss brands tend to have a larger impact on the market, whereas in New Zealand, the sport is more dependent on import products by foreign brands. Further, athletes, events and resorts in New Zealand are often dependent on large brand sponsorships from abroad such as from brand headquarters in the Unites States. Thus, due to its location in the centre of Europe, Swiss brands can take advantage of brands which are closer in proximity and culture to sponsor athletes and events. In terms of media coverage, winter sports in New Zealand tend to have a minor coverage and tradition in local mass media, which leads to less exposure, recognition and investment into the sport. This is also related to how snowboarding is more integrated into other winter sports in New Zealand. Another difference is the accessibility of the ski resort by the population. While in Switzerland the resorts are mostly being visited by day-travelers, ‘weekend warriors’ and holiday makers, the location of the resorts in New Zealand make it diffi cult to visit for one day. This is in part due to the fact that Swiss ski resorts and villages are usually the same location and are accessible through public transportation, while the ski resorts in New Zealand have been built separately from the villages. Further, the villages have not been built to accommodate to high tourist arrivals. Thus, accommodation and food facilities are limited and there is a lack of public transportation to the resorts. Discussion: The fi ndings show that networks and social relations combined with specifi c knowledge on scene-related attributes are crucial in obtaining opportunities within the sport. Partnerships as well as competition between these different actors are necessary for core acceptance, peer credibility and successful commercial interests. Brands need to maintain effective marketing strategies and identities which incorporate subcultural forms of behavior and communication. In order to sustain credibility from its fans, athletes and other snowboarding actors, brands need to maintain their insider status through social networks and commercial branding strategies. The interaction between all actors is a reciprocated process, where social capital, networks and identities are being shared. While the overall structure of snowboard subcultures in Europe and New Zealand are similar, there are some distinct characteristics which make each one unique. References Adjouri, N. & Stastny, P. (2006). Sport-Branding: Mit Sport-Sponsoring zum Markenerfolg. Wiesbaden: Gabler. Glaser, B. & Strauss, K. (1967). The discovery of grounded theory: Strategies for qualitative research. Chicago: Aldine. Hebdige, D. (2009). Subculture; The meaning of style. New York: Routledge. Hitzler, R. & Niederbacher, A. (2010). Leben in Szenen: Formen juveniler Vergemeinschaftung heute. Wiesbaden: Verlag für Sozialwissenschaften. Mayring, P. (2010). Qualitative Inhaltsanalyse: Grundlagen und Techniken. Weinheim: Beltz. Schwier, J. (2006). Repräsentationen des Trendsports. Jugendliche Bewegungskulturen, Medien und Marketing. In: Gugutzer, R. (Hrsg.). body turn. Perspektiven der Soziologie des Körpers und des Sports. Bielefeld: transcript (S. 321-340). Stegbauer, C. (2008). Netzwerkanalyse und Netzwerktheorie. Ein neues Paradigma in den Sozialwissenschaften. Wiesbaden: VS Verlag für Sozialwissenschaften. Thorpe, H. (2011). Snowboarding bodies in theory and practice. Basingstoke: Palgrave Macmillan. Wheaton, B. (2005). Understanding lifestyle sports; consumption, identity and difference. New York: Routledge.

The role of commercial actors in snowboarding

Commercial actors play an essential role in the organisational structure of snowboarding by sponsoring athletes, arranging events, contributing to product development and developing long-term partnerships with other key actors. However, the particularities of their role in the alternative sports cultures which are related to brand marketing strategies have not been extensively researched. Based on Hitzler and Niederbachers (2010) framework of social scenes, Stegbauers (2008) social network and Adjouri and Stastnys (2006) branding theories, analysis is carried out using an ethnographic approach. This includes participant observation of relevant events and semi-structured interviews with over forty key actors of the sport to examine the roles and activities of core actors within snowboarding. The findings reveal that brands have gained an important position within the scene; where they can build partnerships with other core and periphery actors in order to market particularly identities, lifestyles and products. This contributes to the development of a sport which is dependent on brands for its continuity. By using promotional strategies of sponsoring athletes, organising events and feeding media with scene-related content, the aesthetical values of the snowboarding sport are communicated and transferred, while ensuring exposure of the brand’s image and lifestyle. Social contacts as well as knowledge on particularities of the sport allow the commercial actors to gain an influential position and identity within the snowboarding core culture. Keywords: commercial actors, alternative sport cultures, social networks, brands, snowboarding References Adjouri, N. & Stastny, P. (2006). Sport-Branding: Mit Sport-Sponsoring zum Markenerfolg. Wiesbaden: Gabler. Hitzler, R. & Niederbacher, A. (2010). Leben in Szenen: Formen juveniler Vergemeinschaftung heute. Wiesbaden: VS Verlag für Sozialwissenschaften. Stegbauer, C. (2008). Netzwerkanalyse und Netzwerktheorie. Ein neues Paradigma in den Sozialwissenschaften. Wiesbaden: VS Verlag für Sozialwissenschaften.

Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo.

BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-α may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. RESULTS miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. CONCLUSIONS The specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.

Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

BACKGROUND Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. AIM We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. METHODS To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. RESULTS Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. CONCLUSIONS Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

Role of electrophysiological studies in predicting risk of ventricular arrhythmia in early repolarization syndrome.

BACKGROUND The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER pattern are not fully defined. OBJECTIVES This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome. METHODS In a multicenter study, 81 patients with ER syndrome (age 36 ± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations. RESULTS Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 ± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 ± 0.11 mV vs. 0.21 ± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio [OR]: 0.96 [95% confidence interval (CI): 0.33 to 2.81]; p = 0.95; lateral, OR: 1.57 [95% CI: 0.35 to 7.04]; p = 0.56; inferior and lateral, OR: 0.83 [95% CI: 0.27 to 2.55]; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern. CONCLUSIONS Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.

Clinical role of atrial arrhythmias in patients with arrhythmogenic right ventricular dysplasia

BACKGROUND: The clinical role of atrial fibrillation/atrial flutter (AF-AFl) and variables predicting these arrhythmias are not well defined in patients with arrhythmogenic right ventricular dysplasia (ARVD). We hypothesized that transthoracic echocardiography (TTE) and 12-lead electrocardiography (ECG) would be helpful in predicting AF-AFl in these patients. METHODS AND RESULTS: ECGs and TTEs of 90 patients diagnosed with definite or borderline ARVD (2010 Task Force Criteria) were analyzed. Data were compared in (1) patients with AF-AFl and (2) all other patients. A total of 18 (20%) patients experienced AF-AFl during a median follow-up of 5.8 years (interquartile range 2.0-10.4). Kaplan-Meier analysis revealed reduced times to AF-AFl among patients with echocardiographic RV fractional area change <27% (P<0.001), left atrial diameter ≥24.4 mm/m(2)(parasternal long-axis, P=0.001), and right atrial short-axis diameter ≥22.1 mm/m(2)(apical 4-chamber view, P=0.05). From all ECG variables, P mitrale conferred the highest hazard ratio (3.37, 95% confidence interval 0.92-12.36, P=0.067). Five patients with AF-AFl experienced inappropriate implantable cardioverter-defibrillator (ICD) shocks compared with 4 without AF-AFl (36% vs. 9%, P=0.03). AF-AFl was more prevalent in heart-transplant patients and those who died of cardiac causes (56% vs. 16%, P=0.014). CONCLUSIONS: AF-AFl is associated with inappropriate ICD shocks, heart transplantation, and cardiac death in patients with ARVD. Evidence of reduced RV function and atrial dilation helps to identify the ARVD patients at increased risk for AF-AFl.