Intergenerational relations of second-generation immigrants in Switzerland

Intergenerational relations have come to belong to the most important relations in the 21st century. Our Western societies have seen unprecedented immigration, with a considerable number of immigrants already belonging to the second generation. Contrary to their parents, who were socialized into one culture, the second-generation naturally gets acculturated into two cultures (i.e., the parent’s and the host country’s culture). This has important implications for the intergenerational relations of immigrants and their well-being. However, there are only few European studies investigating the role of acculturation in intergenerational relations and well-being in ethnically diverse samples of adult second-generation immigrants. This dissertation had three goals: (1) to investigate feelings of indebtedness toward the parents, a new concept called sense of indebtedness toward the parents (SIP) in association to the established concepts of filial obligations and support exchange in intergenerational research. (2) to understand the role of acculturation for the consensus on filial obligations and its relevance for relationship quality and support exchange with parents. And (3) to shed light on the association of acculturation with well-being. Study 1 suggested that SIP is a reliable and valid measure among second-generation immigrants and positively linked to filial obligations and support given to parents in line with the study hypotheses. Study 2 showed a mediating effect of the consensus on filial obligations on the association between the ethnic culture (i.e., the culture of the parents), but not the host culture and intergenerational relations. Mediation effects were significant among women, but not men. Study 3 demonstrated a positive link between acculturation and well-being. However, a high orientation toward either culture seemed to be more beneficial for well-being than a high orientation toward both cultures at the same time, contrary to the study hypothesis. This dissertation suggests that a high orientation toward the ethnic culture seems to promote positive, intimate, and supportive intergenerational relations among second-generation immigrants. A high orientation toward the host culture might hinder good intergenerational relations, while fostering well-being. Taken together, this indicates, that both cultures play an important role in the immigrants’ lives. Navigating them successfully still poses a challenge to adult Swiss second-generation immigrants. Future studies should aim to investigate the importance of both cultures in specific contexts, to include further aspects of intergenerational relations in research and to study other minorities to draw a more conclusive picture of intergenerational relations

Optimization of High Field Asymmetric Waveform Ion Mobility Spectrometry to enhance the comprehensiveness of mass spectrometry-based proteomic analyses

La grande complexité des échantillons biologiques peut compliquer l'identification des protéines et compromettre la profondeur et la couverture des analyses protéomiques utilisant la spectrométrie de masse. Des techniques de séparation permettant d’améliorer l’efficacité et la sélectivité des analyses LC-MS/MS peuvent être employées pour surmonter ces limitations. La spectrométrie de mobilité ionique différentielle, utilisant un champ électrique élevé en forme d'onde asymétrique (FAIMS), a montré des avantages significatifs dans l’amélioration de la transmission d'ions peptidiques à charges multiples, et ce, en réduisant les ions interférents. Dans ce contexte, l'objectif de cette thèse était d'explorer les capacités analytiques de FAIMS afin d'élargir à la fois la gamme dynamique de détection des protéines/peptides et la précision des mesures en protéomique quantitative par spectrométrie de masse. Pour cela, nous avons systématiquement intégré FAIMS dans des approches classiques en protéomique afin de déterminer les changements dynamiques du protéome humain en réponse à l’hyperthermie. Nous avons d’abord étudié les avantages de FAIMS par rapport à la quantification par marquage isobare (tandem mass tag, TMT). Cette approche permet le marquage d'ions peptidiques avec différents groupements chimiques dont les masses nominales sont identiques mais différant par leur distribution respective d'isotopes stables. Les ions peptidiques marqués par TMT produisent des ions rapporteurs de masses distinctes une fois fragmentés en MS/MS. Malheureusement, la co-sélection d'ions précurseurs conduit souvent à des spectres MS/MS chimériques et une approche plus lente basée sur le MS3 est nécessaire pour une quantification précise. Comme FAIMS améliore l’efficacité de séparation en transmettant sélectivement des ions en fonction de leur voltage de compensation (CV), nous avons obtenu moins de co-sélection de peptides. FAIMS a amélioré la quantification des peptides TMT au niveau MS2 et a permis d’obtenir 68% plus de peptides quantifiés par rapport aux analyses LC-MS/MS classiques, fournissant ainsi un aperçu plus vaste des changements dynamiques du protéome humain en réponse au stress thermique. De plus, nous avons étudié le marquage métabolique par incorporation d’acides aminés marqués par des isotopes stables en culture cellulaire (SILAC). Si des interférences co-éluent avec les isotopes SILAC, la quantification devient imprécise et les contreparties de SILAC peuvent être assignées de manière erronée aux ions interférants du chromatogramme, faussant ainsi le rapport SILAC. Le fractionnement post-ionisation FAIMS pourrait filtrer les ions appartenant au bruit de fond qui pourraient autrement être attribués à une paire ou à un triplet SILAC pour la quantification. Dans ce projet, FAIMS a été particulièrement bénéfique pour les espèces peu abondantes et s’est montré plus performant que le fractionnement par échange de cations (SCX). En outre, FAIMS a permis la séparation des phosphoisomères fréquemment observés dans les extraits complexes de phosphoprotéomes. Le troisième objectif de ce travail de recherche était d'explorer la séparation de l'état de charge et la transmission améliorée de peptides fortement chargés avec FAIMS et son application à l'analyse de peptides SUMOylés. FAIMS pourrait ainsi améliorer la transmission des peptides SUMOylés triplement chargés par rapport aux peptides tryptiques usuels, lesquels sont principalement doublement chargés. Ceci permettait l'enrichissement en phase gazeuse des ions peptides SUMOylés. FAIMS est une approche alternative plus simple pour fractionner les peptides SUMOylés, ce qui réduit les pertes d’échantillon et permet de simplifier le traitement des échantillons, tout en augmentant l’efficacité de séparation de manière plus automatisée et en ajoutant un ordre de grandeur de sensibilité. Le dernier objectif de cette thèse était d’améliorer l’instrumentation de FAIMS en le jumelant aux instruments à la fine pointe de la technologie. Avec un nouveau dispositif FAIMS, développé par nos collaborateurs chez Thermo Fisher Scientific, nous avons montré une amélioration dans la robustesse et la transmission des ions pour la nouvelle interface. Dans des expériences simples en protéomique shotgun, FAIMS a étendu la gamme dynamique d'un ordre de grandeur pour une couverture protéomique plus profonde par rapport aux analyses LC-MS/MS classiques. En outre, le fractionnement en phase gazeuse de FAIMS a généré moins d’analyses chimériques en MS2, ce qui a permis d’obtenir plus d’identifications et une meilleure quantification. Pour ce faire, nous avons directement comparé le LC-FAIMS-MS/MS au LC-MS/MS/MS en utilisant la sélection de précurseur synchrone (SPS) avec et sans fractionnement en phase inverse basique. Des mesures quantitatives comparables ont été obtenues pour toutes les méthodes, à l'exception du fait que FAIMS a parmi d’obtenir un nombre 2,5 fois plus grand de peptides quantifiables par rapport aux expériences sans FAIMS. Globalement, cette thèse met en évidence certains des avantages que FAIMS peut offrir aux expériences en protéomique en améliorant à la fois l'identification et la quantification des peptides.The high complexity of biological samples can confound protein identification and compromise the depth and coverage of mass spectrometry-based proteomic analyses. Separation techniques that provide improved peak capacity and selectivity of LC-MS/MS analyses are often sought to overcome these limitations. High-field asymmetric waveform ion mobility spectrometry (FAIMS), a differential ion mobility device, has shown significant advantages by enhancing the transmission of multiple-charged peptide ions by reducing singly-charged interferences. In this context, the goal of this thesis was to explore the analytical capabilities of FAIMS to extend both the dynamic range of proteins/peptides detection and the precision of quantitative proteomic measurements by mass spectrometry. For this, we systematically integrated FAIMS in standard workflows to monitor the dynamic changes of the human proteome in response to hyperthermia. We first studied the merits of FAIMS to aid isobaric labeling quantification with tandem mass tags (TMT). This approach allows the labeling of peptide ions with different chemical groups of identical nominal masses but differing in their respective distribution of stable isotopes. TMT-labeled peptide ions produce reporter ions of distinct masses once fragmented by MS/MS. Unfortunately, the co-selection of precursor ions often leads to chimeric MS/MS spectra, and a slower MS3 centric approach is needed for precise quantification. Since FAIMS improves peak capacity by selectively transmitting ions based on their compensation voltage (CV), we obtained less peptide co-selection. FAIMS improved TMT quantification at the MS2 level and achieved 68 % more quantified peptides compared to regular LC-MS/MS, providing a deeper insight into the dynamic changes of the human proteome in response to heat stress. Further, we investigated stable isotope labeling by amino acids in cell culture (SILAC) quantification. If interferences co-elute simultaneously with SILAC isotopomers, quantification becomes inaccurate and SILAC counterparts can be missassigned to interfering ions in the highly populated chromatogram, thus skewing the SILAC ratio. FAIMS post-ionization fractionation could filter out background ions that can otherwise be attributed to a SILAC pair/triplet for quantification. In this work, FAIMS was especially beneficial for low abundant species and outperformed the standard strong cation exchange (SCX) fractionation workflow. In addition, FAIMS allowed the separation of phosphoisomers that are frequently observed in complex phosphoproteome extracts. The third aim of this work explored the charge state separation and enhanced transmission of highly charged peptides with FAIMS and its application for SUMOylated peptide analysis. FAIMS could enhance the transmission of triply charged SUMOylated peptides over typical tryptic peptide that are predominantly doubly charged, by applying more negative CVs with FAIMS. This allowed for gas-phase enrichment of SUMOylated peptide ions. FAIMS is an alternate and more straightforward approach to fractionate SUMOylated peptides that reduced sample loss, avoided sample processing, while increasing peak capacity in a more automated manner and added one order of magnitude in sensitivity. The last aim of this thesis was to improve the FAIMS instrumentation by interfacing it to the latest state-of-the-art instruments. With a new FAIMS device developed by our collaborators at Thermo Fisher Scientific, we demonstrate the robustness and the improved ion transmission for the new interface. In simple shotgun proteomics, FAIMS extended the dynamic range by one order of magnitude for deeper proteome coverage compared to regular LC-MS/MS. Moreover, fewer MS2 chimeric scans were generated with FAIMS gas-phase fractionation, which garnered more identifications and better quantification. For this, we directly compared LC-FAIMS-MS/MS to LC-MS/MS/MS using synchronous precursor selection (SPS) with and without basic reverse phase fractionation. Comparable quantitative measurements were obtained for all methods, except that FAIMS provided a 2.5-fold increase in the number of quantifiable peptides compared with non-FAIMS experiments. Overall, this thesis highlights some of the advantages that FAIMS can provide for proteomics experiments by improving both peptide identification and quantification

Développement de la mobilité ionique pour la détection des sites de sumoylation des protéines

L’utilisation de High-Field Assymetric Waveform Ion Mobility (FAIMS) résulte en une diminution significative du bruit de fond en LC-MS. Grâce au fractionnement effectué, il est possible d’identifier des peptides de faible abondance par LCMS/ MS. La performance de FAIMS a été testée en comparant des analyses de digestats trypsiques de lysat de cellules HEK293 avec et sans FAIMS par LCMS/ MS. 8260 peptides ont été identifiés (1165 protéines) avec FAIMS et seulement 4820 peptides (734 protéines) sans FAIMS. Quand un nombre représentatif de peptides synthétiques SUMO ont été ajoutés dans un digestat de HEK293, les analyses nano-LC MS ont montré une limite de détection 18 fois plus faible lorsque FAIMS y est couplé. Finalement, la sumoylation est une des premières réponses cellulaires au stress thermique. Donc pour augmenter la concentration de protéines sumoylées, nous avons effectué un choc thermique (43°C) sur des cellules HEK293 exprimant SUMO3 mutante. Un enrichissement de SUMOIylation dans la fraction nucléaire a été observé après 60 min par immunobuvardage. Une analyse LC-FAIMS-MS/MS a donné une augmentation de 2 fois du nombre de peptides SUMOylés identifiés après choc thermique.SUMOylation is a post-translational modification of proteins that is involved in different cellular processes including mitosis, DNA replication and transcription. However its detection by liquid chromatography coupled to mass spectrometry (LC-MS) can be challenging due to its low abundance and dynamic regulation. High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) helps in eliminating background ions which allows to improve the limit of detection. FAIMS separation is based on the differential mobility of ions between low to high electric field. In a preliminary experiment performed on a tryptic digest of HEK293 proteins, we identified 8260 peptides (1165 proteins) with FAIMS compared to 4820 peptides (734 proteins) without FAIMS. The limit of detection was 12 fmol with FAIMS for synthetic SUMO peptides spiked in a complex tryptic digest and 183 fmol without FAIMS. A LC-MS analysis with FAIMS of a mutant SUMO3 HEK293 cell line resulted in a 3-fold increase in the identification of SUMO peptides

Integrierte psychotherapeutische Behandlung von schwer psychisch Kranken: Zwischen Wünschbarkeit und Versorgungsrealität

Zusammenfassung: In den letzten 3Jahrzehnten hat sich die Behandlung von Menschen mit schweren psychischen Erkrankungen nachhaltig verändert. Das Bestreben, ein gemeindenahes, niederschwelliges Versorgungsangebot für diese Personengruppe bereitzustellen, hat zu einer Diversifizierung von gemeindepsychiatrischen Behandlungs-, Wohn- sowie Rehabilitationseinrichtungen für die Arbeitsintegration geführt. Auch die Behandlung akuter Krankheitsphasen erfolgt vermehrt gemeindenah und ambulant. Unabhängig davon wurde eine Reihe von Psychotherapieansätzen für die gleiche Patientengruppe entwickelt, die trotz ihrer Evidenzbasierung nur begrenzt Eingang in die psychiatrische Regelversorgung gefunden hat. Die Koordination verschiedener Versorgungsstrukturen und ihre Verknüpfung mit evidenzbasierten psychotherapeutischen Behandlungsinhalten sind deshalb Eckpfeiler der Weiterentwicklung. Diese Arbeit skizziert den gegenwärtigen Entwicklungsstand und vermittelt einen Überblick über die verschiedenen evidenzbasierten Psychotherapieansätze, die angesichts der Behandlungs- und Rehabilitationsziele wichtige Komponenten einer patientenzentrierten integrierten Versorgung von schwer und anhaltend psychisch Kranken bilde

Impaired Poststenotic Aortic Pulsatility After Hemodynamically Ideal Coarctation Repair in Children

Using echocardiographic quantification of aortic pulsatility distal to the site of the surgical anastomosis, we evaluated whether the preoperatively impaired poststenotic aortic pulsatility returned to normal after repair of coarctation with a hemodynamically ideal result. Patients who underwent repair of aortic coarctation without residual obstruction were compared to a matched group of normal children. A standardized M-mode echocardiographic evaluation of the aorta at the diaphragmatic level was performed for all patients. Measurements consisted of maximum and minimum aortic diameters, time intervals, and a calculated pulsatility index. Compared to normal children (n = 19), 20 children with operated coarctation and with a hemodynamically ideal result showed a significantly smaller increase in aortic diameter in systole (mean of 29 ± 7% in patients versus 37 ± 7% in normals; p < 0.01). In contrast to patients with coarctation in whom the maximum aortic distension is reached much later during the cardiac cycle, hemodynamically normalized, operated patients in our study had no such delay (maximum aortic pulsation at 28% of cardiac cycle time compared to 27% in normals; p = not significant). The pulsatility index of the poststenotic aorta was clearly lower in operated children (mean, 130 ± 50%/sec) compared to a normal mean value of 202 ± 33%/sec but was still significantly higher than that in patients with unoperated coarctation, who showed a low mean value of 51 ± 24%/sec (p < 0.01). After correction of aortic coarctation with a hemodynamically ideal result, the pulsatility of the poststenotic aorta, severely impaired prior to repair, did not return to normal during the observation period in the patients studie

Non-governmental refuse collection systems

Non-governmental refuse collection system

High-frequency jet ventilation for minimizing breathing-related liver motion during percutaneous radiofrequency ablation of multiple hepatic tumours

Movements of the liver caused by spontaneous breathing (during sedation or local anaesthesia) or by ventilation during anaesthesia are a source of concern in CT-guided procedures because of the limited spatial and contrast resolution of unenhanced imaging, artifacts caused by the probes and the relatively low temporal resolution of the fluoroscopy mode. During CT-guided radiofrequency ablation (RFA), it is essential that the lesion can be visualized optimally and that the ablation probe is positioned accurately to avoid non-target injuries. We therefore used high-frequency jet ventilation and general anaesthesia to minimize ventilation-related liver movement and provide optimal conditions for a patient undergoing RFA of hepatic metastases. The technical and anaesthetic considerations are discussed, and a specific limitation of transcutaneous Pco2 measurement during activation of the ablation is reported for the first tim

The Use of the "Preclosure” Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

Purpose: This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Methods: Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide® 6F, Abbott) was placed before arterial sheath (mean 9F, range 6-12F) introduction in 101 patients (74 men, 73%, mean age 70.1±12.6years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. Results: There were a total of 19 vascular complications (19%) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2%) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94%); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. Conclusions: With acceptable short- and mid-term outcomes, the "preclose” technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectom

Infantile scimitar syndrome with severe pulmonary hypertension: successful treatment with coil embolization of the systemic arterial supply to the sequestered lung

Scimitar syndrome is a rare cardiopulmonary malformation. Presentation in infancy is usually associated with pulmonary hypertension and severe symptoms. We discuss treatment of such an infant. Two abnormal systemic vessels supplying the sequestered lower part of the right lung were embolized using catheter-inserted coils. The patent arterial duct was surgically ligated. These procedures resulted in a significant reduction of the shunt and the level of pulmonary hypertension, as well as in an impresssive improvement of symptom