Occupational and patient exposure as well as image quality for full spine examinations with the EOS imaging system.

PURPOSE: EOS (EOS imaging S.A, Paris, France) is an x-ray imaging system that uses slot-scanning technology in order to optimize the trade-off between image quality and dose. The goal of this study was to characterize the EOS system in terms of occupational exposure, organ doses to patients as well as image quality for full spine examinations. METHODS: Occupational exposure was determined by measuring the ambient dose equivalents in the radiological room during a standard full spine examination. The patient dosimetry was performed using anthropomorphic phantoms representing an adolescent and a five-year-old child. The organ doses were measured with thermoluminescent detectors and then used to calculate effective doses. Patient exposure with EOS was then compared to dose levels reported for conventional radiological systems. Image quality was assessed in terms of spatial resolution and different noise contributions to evaluate the detector's performances of the system. The spatial-frequency signal transfer efficiency of the imaging system was quantified by the detective quantum efficiency (DQE). RESULTS: The use of a protective apron when the medical staff or parents have to stand near to the cubicle in the radiological room is recommended. The estimated effective dose to patients undergoing a full spine examination with the EOS system was 290μSv for an adult and 200 μSv for a child. MTF and NPS are nonisotropic, with higher values in the scanning direction; they are in addition energy-dependent, but scanning speed independent. The system was shown to be quantum-limited, with a maximum DQE of 13%. The relevance of the DQE for slot-scanning system has been addressed. CONCLUSIONS: As a summary, the estimated effective dose was 290μSv for an adult; the image quality remains comparable to conventional systems.

Neurobiology of addiction: the role of transcription factors CREB and C/EBP as well as that of their coactivators

Résumé Le présent travail de thèse a fait face au défi de lier les changements transcriptionnels dans les neurones du système nerveux central au développement de l'addiction aux drogues. I1 est connu que l'apprentissage induit des modifications au niveau de la structure du cerveau, principalement en changeant la manière dont les neurones sont interconnectés par des synapses. De plus en plus d'évidences soutiennent un scénario selon lequel l'activité neuronale déclenche des cascades de signalisation intracellulaire qui ciblent des facteurs de transcription. Ces derniers peuvent activer la transcription de gènes spécifiques qui codent pour des protéines nécessaires au renforcement des synapses mémorisant ainsi la nouvelle information. Puisque l'addiction peut être considérée comme une forme aberrante d'apprentissage, et que les modifications synaptiques sont connues pour être impliquées dans le processus d'addiction, nous essayons de décrire des mécanismes transcriptionels étant à la base des changements synaptiques induits par les drogues. Comme modèle nous utilisons des cultures primaires des neurones de striatum, d'hippocampe et de cortex de souris ainsi que des tranches de cerveau de rat. Une des caractéristiques communes de quasiment toutes les substances addictives est de pouvoir activer le système mésolimbique dopaminergique provoquant la libération de dopamine sur les neurones du striatum (du noyau accumbens). Dans ce travail de thèse nous démontrons que dans des cultures du striatum, la dopamine induit le facteur de transcription C/EBPβ qui, à son tour, provoque l'expression du gène codant pour la substance P. Ce mécanisme pourrait potentiellement contribuer à la tolérance envers les drogues puisqu'il fait partie d'une rétroaction (feed-back) sur les cellules produisant la dopamine. Etant donné que ces résultats montrent l'importance de C/EBPβ dans la psychopathologie de l'addiction, nous avons également décidé d'étudier les mécanismes fondamentaux de l'activation de la transcription par C/EBPβ. Nos expériences démontrent que trois isoformes activatrices de la famille C/EBP recrutent le coactivateur CBP et provoquent en même temps sa phosphorylation. Enfin, nous montrons que les coactivateurs nommés TORC, nouvellement découverts et clonés, sont capables de détecter la coïncidence d'un signal cAMP et d'une entrée de calcium dans des neurones. Par conséquent les TORCs pourraient contribuer à détecter la coïncidence d'un signal glutamate et d'un signal dopamine dans les neurones de striatum, ce qui pourrait être important pour associer les effets hédonistes de la drogue à l'information contextuelle (par exemple à l'environnement où la drogue a été consommée). Nous sommes les premiers à observer que les TORCs sont nécessaires pour la potentiation à long terme dans l'hippocampe. Summary The present thesis work faced the challenge to link the development of drug addiction to transcriptional changes in the neurons of the central nervous system. Experience and learning are known to induce structural modifications in the brain, and these changes are thought to occur mainly in the way neurons are interconnected by synapses. More and more evidences point to a scenario in which neuronal activity would activate signalization cascades that impinge on transcription factors, which, in turn, would activate genes necessary for the reinforcement of synapses coding for new informations. Given that drug addiction can be considered as an aberrant form of learning and is thought to involve synaptic modifications, we try to elucidate some of the transcriptional mechanisms that could underlie drug-induced synaptic changes. As a model system, we use primary cultures of striatal, cortical and hippocampal neurons dissected from mouse embryos as well as brain slices from rats. One of the common features of virtually all drugs of abuse is to activate the mesocorticolimbic dopaminergic system that results in the release of dopamine onto the neurons of the striatum (nucleus accumbens). In this thesis work we show that in striatal cultures, dopamine induces the transcription factor C/EBPβ that in turn drives the expression of the gene coding for substance P. This mechanism is likely to be important for the drug-induced tolerance in the brain since it might be a part of a feedback acting on dopaminergic neurons. Given the suspected importance of C/EBPβ in drug addiction, we also try to elucidate some aspects of the basic mechanisms by which the C/EBP family activates transcription. We show that three activating members of the C/EBP family recruit the coactivator CBP and trigger its phosphorylation. Finally, we demonstrate that the newly discovered and cloned transcriptional coactivators, named TORCs (transducers of regulated CREB activity) are able to detect the coincidence of a calcium and a cAMP signal in the central nervous system. This way, TORCs could contribute to the detection of a coincidence between a glutamate and a dopamine signal in striatal neurons - a process that is suggested to be important for an association between the rewarding effect of a drug and contextual information (such as the environment where the drug had been taken). We demonstrate that TORCs are required for hippocampal LTP.

Modelling of iron-filled magneto-active polymers with a dispersed chain-like microstructure

Magneto-active polymers are a class of smart materials commonly manufactured by mixing micron-sized iron particles in a rubber-like matrix. When cured in the presence of an externally applied magnetic field, the iron particles arrange themselves into chain-like structures that lend an overall anisotropy to the material. It has been observed through electron micrographs and X-ray tomographs that these chains are not always perfect in structure, and may have dispersion due to the conditions present during manufacturing or some undesirable material properties. We model the response of these materials to coupled magneto-mechanical loading in this paper using a probability based structure tensor that accounts for this imperfect anisotropy. The response of the matrix material is decoupled from the chain phase, though still being connected through kinematic constraints. The latter is based on the definition of a 'chain deformation gradient' and a 'chain magnetic field'. We conclude with numerical examples that demonstrate the effect of chain dispersion on the response of the material to magnetoelastic loading.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended.

OBJECTIVES: Immunohistochemistry (IHC) has become a promising method for pre-screening ALK-rearrangements in non-small cell lung carcinomas (NSCLC). Various ALK antibodies, detection systems and automated immunostainers are available. We therefore aimed to compare the performance of the monoclonal 5A4 (Novocastra, Leica) and D5F3 (Cell Signaling, Ventana) antibodies using two different immunostainers. Additionally we analyzed the accuracy of prospective ALK IHC-testing in routine diagnostics. MATERIALS AND METHODS: Seventy-two NSCLC with available ALK FISH results and enriched for FISH-positive carcinomas were retrospectively analyzed. IHC was performed on BenchMarkXT (Ventana) using 5A4 and D5F3, respectively, and additionally with 5A4 on Bond-MAX (Leica). Data from our routine diagnostics on prospective ALK-testing with parallel IHC, using 5A4, and FISH were available from 303 NSCLC. RESULTS: All three IHC protocols showed congruent results. Only 1/25 FISH-positive NSCLC (4%) was false negative by IHC. For all three IHC protocols the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) compared to FISH were 96%, 100%, 100% and 97.8%, respectively. In the prospective cohort 3/32 FISH-positive (9.4%) and 2/271 FISH-negative (0.7%) NSCLC were false negative and false positive by IHC, respectively. In routine diagnostics the sensitivity, specificity, PPV and NPV of IHC compared to FISH were 90.6%, 99.3%, 93.5% and 98.9%, respectively. CONCLUSIONS: 5A4 and D5F3 are equally well suited for detecting ALK-rearranged NSCLC. BenchMark and BOND-MAX immunostainers can be used for IHC with 5A4. True discrepancies between IHC and FISH results do exist and need to be addressed when implementing IHC in an ALK-testing algorithm.

The contribution of individual and professional characteristics to general and work-related well-being

Cette thèse porte sur la contribution des caractéristiques individuelles et des situations professionnelles au bien-être. En combinant différentes perspectives théoriques, notamment la théorie de la construction de la carrière, la théorie de la justice organisationnelle, les modèles du bien-être au travail, et les conceptualisations de l'incivilité au travail, un certain nombre d'hypothèses sont proposées concernant le lien entre certaines caractéristiques individuelles et situationnelles et le bien-être général et professionnel. Les deux premières études se focalisent sur la validation d'une échelle d'adaptabilités de carrière et sur le rôle médiateur de cette adaptabilité dans la relation entre des dispositions et le bien-être. La troisième étude évolue l'hypothèse d'un possible effet de médiation de l'adaptabilité mais cette fois de la relation entre insécurité professionnelle et charge de travail d'une part et le bien-être d'autre part. La quatrième étude adopte une perspective longitudinale et analyse les associations entre les dimensions de la personnalité, l'adaptabilité de carrière et le bien-être dans quatre parcours professionnels différents. La cinquième étude porte sur une autre caractéristique individuelle, à savoir la croyance en un monde juste. Cette étude illustre comment la croyance en un monde juste influence les perceptions de justice organisationnelle une année après, qui ont une incidence importante sur le bien-être. Enfin, la dernière étude se concentre sur une population spécifique, les immigrants en Suisse, et souligne qu'être la cible d'incivilité sur le lieu de travail est généralement liée au pays d'origine. Globalement, cette thèse met en évidence que les caractéristiques individuelles ont des effets tant directs qu'indirects sur le bien-être et que ces mêmes caractéristiques explique en partie, les relations entre la situation professionnelle et le bien-être. Plus spécifiquement, des situations professionnelles peuvent influencer l'expression de certaines caractéristiques individuelles, soit en contribuant à leurs activations ou à leurs inhibitions. De plus, l'impact des caractéristiques individuelles sur le bien-être semble dépendre de la situation professionnelle. Il est donc important de considérer les influences simultanées et réciproques des caractéristiques individuelles et de la situation contextuelle et professionnelle pour rendre compte du bien-être général et professionnel. -- This thesis explores how individual characteristics and professional situations correspond to well-being. Drawing from various theoretical backgrounds, such as career construction theory, justice theory, models of job strain, and theories on subtle discrimination, a number of specific hypotheses are put forward pertaining to a selection of individual and professional aspects as well as general and work-related well-being. The six studies presented in this thesis focus on specific aspects and adopt different methodological and theoretical approaches. The first two studies concern the validation of the career adapt-abilities scale and test the potential of career adapt-abilities to mediate the relationship between dispositions and outcomes. The third study extends the hypothesis of career adapt-abilities as a mediator and finds that it mediates the effects of job insecurity and job strain on general and professional well-being. The fourth study adopts a longitudinal approach and tests the associations between personality traits and career adaptability and well-being in four different professional situations. Study five concerns another individual characteristic, belief in a just world, and illustrates how justice beliefs drive perceptions of organizational justice, which in turn impact, on well-being outcomes one year later. The final study focuses on the professional experiences of a specific population, immigrants in Switzerland, and confirms that being a target of incivilities is related to national origin. Globally, this thesis finds that individual characteristics have direct and indirect influences on well-being and that these characteristics may also mediate the associations between professional situations and outcomes. In particular, the professional situation may alter the display of individual characteristics, either by contributing to their activation or their depletion, and the ways in which individual factors influence well-being does seem to depend on the professional situation. It is thus necessary to adopt a "both...and" perspective when studying the impact of individual and professional characteristics as these factors mutually influence each other.

Validity of the FACIT-Sp to assess spiritual well-being in elderly patients

Among instruments measuring spiritual well-being, the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp-12) is the most widely used instrument in research. It has been validated in patients suffering from cancer or HIV/AIDS, but has rarely been used in elderly patients. The objectives of this study were to determine the psychometric properties and suitability of the FACIT-Spto assess spiritual well-being in hospitalized elderly patients. This cross-sectional study uses a mixed method approach. Subjects were patients (N = 208), aged 65 years and older, consecutively admitted in post-acute rehabilitation. Psychometric properties of the FACITSp were investigated. The internal structure of the FACIT-Sp (factor structure and internal consistency) was assessed. Convergent validity of the FACIT-Sp was assessed using the Spiritual Distress Assessment Tool (SDAT), the question "Are you at peace?" and the Geriatric Depression Scale (GDS). Predictive validity was assessed using length of stay (LOS) and discharge destination. Understanding and interpretation of FACIT-Sp items were consecutively assessed in a sub-sample of 135 patients. Results show that FACIT-Sp scores ranged from 7 to 46 (mean 29.6 ± 7.8); 23.1% of the patients had high spiritual well-being. Cronbach's α was g ood ( 0.85). Item-to-total correlations were all significant (0.34 to 0.73). Principal component analyses performed with 2 or 3 factors were only moderately consistent with previous work. FACIT-Sp correlated with SDAT, "Are you at peace?" and GDS (Rho = −0.45, P < 0.001; 0.51, P < 0.001 and −0.38, P < 0.001). No association was found with LOS or discharge destination. Spontaneous comments about one or more FACIT-Sp items were made by 97/135 (71.9%). Specifically, items that address purpose and meaning in life were frequently found difficult to answer. Analyses suggest that the FACIT-Sp may underestimate spiritual well-being in older patients. In conclusion, despite having acceptable psychometric properties, the FACIT-Sp presents limitations for measurement of spiritual well-being in hospitalized elderly patients.

The Articulation of Different Life Domains among Female Senior Managers and Their Subjective Well-Being : Focusing on Meaning Constructions in Everyday Life

Work-life issues have become a major concern across Western societies with the objective to promote women's careers and well-being. However, despite growing attempts to increase the number of women in senior management positions in European countries, such as Switzerland, they remain highly underrepresented. Inspired from the cultural approach in psychology, this article focuses on these women's concrete everyday life to understand how they articulate different life domains and how this influences their subjective well-being. A narrative approach based on reflexivity is adopted to analyze women's activity. Results show meaning intertwinements between life priorities that are often conflicting. Two psychological functions are identified: the feeling of control and the letting go of control. Each of these contributes to women's subjective well-being through the use of diversified supports, but their structuring roles appear only in relation to one another. Results are discussed in the light of existing literature and of their implications.

Labor market experience and well-being after firm closure. Survey evidence on displaced manufacturing workers in Switzerland

This study examines how plant closure affected individuals' careers and lives about two years after they lost their job. We analyze the displaced workers' reemployment prospects and study for reemployed workers the characteristics of their new jobs in terms of reemployment sectors, wages, and job quality. Additionally, we inquire how workers' sociability and subjective well-being were affected by job loss. Our analysis is based on our own survey conducted in Switzerland in 2011. The survey included the workforce of five manufacturing companies that had closed down two years earlier. We addressed the risk of biases typically prevailing with observational data by complementing it with register data from the public unemployment insurance. Moreover, we use a control group based on matched data from the Swiss Household Panel. We find that workers experience strongly diverging outcomes after plant closure: on the one hand, high proportions of the workers experience a smooth transition after plant closure. More than two-thirds of the workers returned to employment, more than half of them within less than six months. With respect to their social lives, we find that positive changes in relationships with their spouse, family and friends are more frequent than negative changes. On the other hand, for a small group of workers plant closure had a detrimental effect. Close to twenty percent remained unemployed. About ten percent of the workers were long-term unemployed and subsequently often were reemployed in jobs of lower quality. Unemployed workers and workers who dropped out of the labor force were particularly prone to find their subjective well-being decreasing. The most vulnerable subgroup in our study were workers over 55. This result stands in striking contrast to a large body of literature that considers labor market institutions to be primarily biased against young workers. Our findings show that older workers not only take longer to find a job but are also less likely to return to employment. Moreover, if they manage to find a job, they experience the severest cuts in wages and job quality of all cohorts. From a life-course perspective this result is remarkable since it shows that workers are not protected from hardship in their late careers. In light of the current demographic changes this finding may have important policy implications. -- Cette étude analyse l'impact des fermetures d'entreprises sur les travailleurs licenciés. Plus précisément, nous examinons les chances de réinsertion des travailleurs dans le marché du travail et - pour ceux qui l'ont fait avec succès - dans quels secteurs, pour quels salaires et avec quelle qualité d'emploi ils sont réengagés. Nous nous intéressons également aux répercussions engendrées par la perte de l'emploi sur la sociabilité et le bien-être subjectif des travailleurs concernés. Notre analyse se base sur les données d'une enquête que nous avons menée en 2011. Cette enquête cible le personnel de cinq entreprises industrielles suisses qui avaient fermé leurs portes deux ans auparavant. Pour dépasser les biais typiques liés aux données d'observation, nous utilisons en complément des données administratives issues de l'assurance chômage publique. De plus, nous utilisons un groupe de contrôle basé sur des données appariées provenant du Panel Suisse de Ménage. Nos analyses montrent des résultats fortement contrastés. D'un côté, la majeure partie des travailleurs ont vécu une transition professionnelle plutôt facile : plus des deux tiers des personnes ont retrouvé un travail et parmi elles plus de la moitié en moins de six mois. Par rapport aux relations sociales, tant avec leur partenaire, qu'avec les membres de leur famille et leurs amis, les changements expérimentés étaient plus fréquemment positifs que négatifs. De l'autre côté, cependant, pour une petite partie de travailleurs la fermeture de leur entreprise a eu des conséquences très négatives sur leur carrière et leur bien-être. Au moment de notre enquête, presque vingt pourcents des travailleurs étaient au chômage. Les personnes au chômage et celles qui avaient quitté le marché du travail ont été particulièrement affectées par une diminution de leur bien-être subjectif. Les plus vulnérables parmi les travailleurs licenciés étaient ceux qui étaient âgés de plus de 55 ans. Notre analyse montre que les travailleurs âgés ont beaucoup moins fréquemment retrouvé un travail. Pour les personnes de plus de 55 ans qui ont tout de même retrouvé un emploi, la réinsertion a durée plus longtemps, les pertes de salaire étaient plus conséquentes et la diminution de la qualité de l'emploi plus grande que pour les autres cohortes. Au vu des changements démographiques actuels, ce résultat interpellant peut avoir des implications politiques importantes.

Social Support, Social and Temporal Comparisons Protect Well-Being and Health between 45 and 70 Years Old in Four Urban Communities

This study examined the impact of social support and of temporal and social comparisons on well-being and selfreported health in four capital cities: Paris, Berlin, Moscow and Beijing. Based on the lifespan control theory, an integrative model investigating the influence of these coping strategies, especially on the psychological regulation of health losses, was tested on 1141 respondents aged 45 to 70 years by using structural equation modelling with multigroup comparisons. Results indicated a good fit of the model to participants' responses. In all contexts, physical weaknesses favoured the use of social and temporal comparison strategies rather than social support. Moreover, across the cities, coping strategies were oriented more toward protecting self-evaluation of health than toward enhancement of well-being. Social comparison decreased the impact of physical weaknesses on health evaluation and on well-being in the four cities, but to a lesser extent in China. Results are discussed regarding the normative cross-cultural aspects that intervene during ageing in the four urban contexts.

Le sentiment de gratitude en soins palliatifs : un facteur contribuant au bien-être et à la qualité de vie ? [Gratitude in palliative care: is it a psychological factor contributing to well-being and quality of life?]

En s'appuyant sur la littérature scientifique et l'état de la recherche, cet article a pour objectif de montrer pourquoi la prise en compte du sentiment de gratitude peut s'avérer utile dans le contexte palliatif en mettant en évidence dans quelle mesure cette émotion ou disposition individuelle: 1) entre en résonance avec le concept de croissance posttraumatique et certains enjeux relationnels chez les patients en fin de vie; 2) représente un facteur favorisant le bien-être et la qualité de vie; 3) peut être considérée comme un facteur protecteur contre les troubles psychopathologiques. Based on the scientific literature and the state of research, this article aims to show why the feeling of gratitude may represent a point of interest for palliative care. We will highlight the following in this article: 1) why this feeling of gratitude resonates with the concept of post-traumatic growth and relational challenges in end-of-life patients; 2) in which measure this feeling represents a factor contributing to well-being and quality of life; 3) in which measure this feeling may be considered as a protective factor against psychopathological troubles.

Added value of SPECT/CT in addition to whole-body scintigraphy augmented with prone lateral views in patients with well-differentiated thyroid carcinoma

Purpose: We aimed to determine the impact of SPECT/CT performed in addition to whole-­‐body scintigraphy augmented with prone lateral views in patients with well-­‐differentiated thyroid carcinoma. Methods and Materials: This retrospective study included 141 patients (87 female, 54 male, mean age 47 years) with well-­‐differentiated thyroid carcinoma (105 papillary, 31 follicular, 1 Hürthle cell and 4 poorly differentiated) treated with radioiodine therapy (1000-7400 MBq). Patients were referred for either first postsurgical therapy (n=76) or further treatment (n=65). Two nuclear medicine physicians interpreted the scans in consensus (first whole-­‐body scintigraphy with prone lateral view, then SPECT/CT) reporting abnormal iodine uptake in the thyroid bed, lymph nodes and distant metastasis. The corresponding ATA risk score was calculated for each patient before and after SPECT/CT, as well as change in disease extension Results: The analysis showed a difference between scintigraphy and SPECT/CT in n=17 lesions in 14 patients (9.9%): 12 were described as suspicious on scintigraphy and could be considered as benign on SPECT/CT (3 corresponded to local iodine uptake, 6 to lymph nodes metastases and 3 to distant metastases). The others 5 corresponded to metastases (4 lymph nodes and 1 distant) that were not seen on whole-­‐body scintigraphy augmented with prone lateral views. In 10 of 141 (7.1%) patients, we observed a change in ATA risk stratification, with a risk increase in 4 of them (2.8%). Conclusion: SPECT/CT allowed detecting 5 focal lesions missed on planar scintigraphy, and to precise benignity of 12 suspicious lesions on planar scintigraphy. Moreover, SPECT/CT improved the risk stratification in 10 patients with a significant change in the patient management