Three essays on the concept of trust and its foundations

The present dissertation focuses on trust and comprises three empirical essays on the concept itself and its foundations. All three essays investigate trust as an expectation and rely on selfreport measures of trust. Whereas the first two chapters investigate social trust, the third chapter investigates political trust. Essentially, there are three related important debates to which the following chapters contribute. A first debate discusses problems with current selfreport measures. Scholars recently started to question whether standard trust questions really measure the same across countries and languages. Chapter 1 engages in this debate. Using data from Switzerland it studies whether different trust questions measure the same latent trust constructs across individuals belonging to three different culturallinguistic regions. The second debate concerns the socalled forms or dimensions of trust. Recently, scholars started investigating whether trust is a onedimensional construct, i.e. whether an individual's trust judgment differs for categories of trustees such as strangers, neighbors, family members and friends or not. Relying on confirmatory factor analysis Chapter 2 investigates whether individuals really do make a difference between different trustee categories and to what extent these judgments can be summarized into higherorder latent trust constructs. The third debate is concerned with causes of differences in trust across humans. Chapter 3 focuses on the role of laterlife experiences, more precisely victimization experiences and investigates their causal relationship with generalized social trust. Chapter 4 focuses on the impact of direct democratic institutions on the trust relationship between citizens and political authorities.

Callus massage after distraction osteogenesis using the concept of lengthening then dynamic plating.

Correction of complex deformities is a challenging procedure. Long-term wearing of a fixator after correction and lengthening are inconvenient and has a high rate of complication. The goals of the surgical treatment in the presented case were: (1) correction of the deformity and lengthening of the left leg by the Taylor spatial frame (TSF, Smith and Nephew, Marl, Germany); (2) reduction in the time the patient wears the TSF by changing the fixation system to a plate (lengthening then plating-LTP) and using a locking compression plate in conjunction with the 5.0 dynamic locking screws in order to accelerate bone healing.

How to assess the external validity of therapeutic trials: a conceptual approach

Background External validity of study results is an important issue from a clinical point of view. From a methodological point of view, however, the concept of external validity is more complex than it seems to be at first glance. Methods Methodological review to address the concept of external validity. Results External validity refers to the question whether results are generalizable to persons other than the population in the original study. The only formal way to establish the external validity would be to repeat the study for that specific target population. We propose a three-way approach for assessing the external validity for specified target populations. (i) The study population might not be representative for the eligibility criteria that were intended. It should be addressed whether the study population differs from the intended source population with respect to characteristics that influence outcome. (ii) The target population will, by definition, differ from the study population with respect to geographical, temporal and ethnical conditions. Pondering external validity means asking the question whether these differences may influence study results. (iii) It should be assessed whether the study's conclusions can be generalized to target populations that do not meet all the eligibility criteria. Conclusion Judging the external validity of study results cannot be done by applying given eligibility criteria to a single target population. Rather, it is a complex reflection in which prior knowledge, statistical considerations, biological plausibility and eligibility criteria all have place.

[Femoroacetabular impingement: trigger for the development of coxarthrosis]

Femoroacetabular impingement (FAI) is frequent; the estimated prevalence ranges between 10 and 15%. Our 10-years experience strongly suggests that FAI leads to osteoarthritis. Isolated acetabular or femoral abnormalities are rare, even though in women acetabular and in men femoral abnormalities predominate. Normal radiographs do not exclude the presence of FAI. Symptoms are related to the degree of deformity and occur earlier in the presence of activities requiring high levels of motion. The majority of patients with FAI are under the age of 40 years.In contrast to impingement in total hip replacement, the natural hip is under much higher constraint, not allowing to escape from impingement-induced shear forces by subluxation or complete dislocation. FAI-induced shear forces due to an aspherical femoral head/neck (cam type) are therefore high, causing outside-in damage with cleavage lesions of the acetabular cartilage by forced flexion and internal rotation. The cartilage of the femoral head remains initially intact, which cannot be explained by the classic concept of osteoarthritis. After the femoral head has migrated into the acetabular cartilage defect, vertical forces contribute to the further course of osteoarthritis. Tears between the labrum and cartilage, as seen by MRI, are not avulsions of the labrum from the cartilage but rather outside-in avulsions of the cartilage from the labrum. In acetabular overcoverage (pincer type) the labrum is the first structure to fail and acetabular cartilage damage develops thereafter.The treatment of FAI in patients under the age of 40 years is aimed at joint preservation. The clinical result is worse in the presence of significant cartilage damage. Therefore, early appreciation of FAI and timely therapeutic intervention as well as professional and athletic adjustment are important if osteoarthritis is to be prevented.

[High altitude pulmonary edema. An experiment of nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans]

High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.

[Experiences of patients and family members during the stay on a nursing unit]

In 2004, the university hospital of Berne ran a pilot project with a Nursing Unit (NU). In this unit patients who no longer needed a close surveillance by physicians were cared for. They needed primarily complex professional nursing care which could not be provided by other hospitals, nursing homes, home care or family members. The nurses were responsible for the coordination of care. This qualitative study investigated experiences of patients and family members with the care concept of the NU. Thematically focused interviews were conducted with nine patients and five family members. Qualitative content analysis was used for data analysis. Results show that patients and family members mostly accepted the new care concept. They positively experienced the quiet and restful atmosphere, the patient-centred and continuous care by competent nurses, the education and the discharge planning. Some study participants reported missing information at the time of their transfer to the NU, insufficient assessments or unsuitable educational scripts. The study provides evidence to positive effects of a patient-centred care approach.

Natural anti-Siglec autoantibodies mediate potential immunoregulatory mechanisms: implications for the clinical use of intravenous immunoglobulins (IVIg)

Human intravenous immunoglobulins (IVIg) contain natural autoantibodies against the inhibitory lectin-receptors Siglec-8 and Siglec-9. These two members of the Siglec family are known to mediate both inhibitory and death signals. Here, we discuss recent findings regarding the cytotoxic effects of natural anti-Siglec autoantibodies on both neutrophils and eosinophils, and present the concept of a novel regulatory mechanism exhibiting anti-inflammatory properties. Consequently, IVIg may amplify this regulatory pathway by increasing the concentration of natural anti-Siglec autoantibodies in blood and tissues.

A Concept of Semantics Extraction from Web Data by Induction of Fuzzy Ontologies

Traditionally, ontologies describe knowledge representation in a denotational, formalized, and deductive way. In addition, in this paper, we propose a semiotic, inductive, and approximate approach to ontology creation. We define a conceptual framework, a semantics extraction algorithm, and a first proof of concept applying the algorithm to a small set of Wikipedia documents. Intended as an extension to the prevailing top-down ontologies, we introduce an inductive fuzzy grassroots ontology, which organizes itself organically from existing natural language Web content. Using inductive and approximate reasoning to reflect the natural way in which knowledge is processed, the ontology’s bottom-up build process creates emergent semantics learned from the Web. By this means, the ontology acts as a hub for computing with words described in natural language. For Web users, the structural semantics are visualized as inductive fuzzy cognitive maps, allowing an initial form of intelligence amplification. Eventually, we present an implementation of our inductive fuzzy grassroots ontology Thus,this paper contributes an algorithm for the extraction of fuzzy grassroots ontologies from Web data by inductive fuzzy classification.

The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment

Recent investigations of the tumor microenvironment have shown that many tumors are infiltrated by inflammatory and lymphocytic cells. Increasing evidence suggests that the number, type and location of these tumor-infiltrating lymphocytes in primary tumors has prognostic value, and this has led to the development of an 'immunoscore. As well as providing useful prognostic information, the immunoscore concept also has the potential to help predict response to treatment, thereby improving decision- making with regard to choice of therapy. This predictive aspect of the tumor microenvironment forms the basis for the concept of immunoprofiling, which can be described as 'using an individual's immune system signature (or profile) to predict that patient's response to therapy' The immunoprofile of an individual can be genetically determined or tumor-induced (and therefore dynamic). Ipilimumab is the first in a series of immunomodulating antibodies and has been shown to be associated with improved overall survival in patients with advanced melanoma. Other immunotherapies in development include anti-programmed death 1 protein (nivolumab), anti-PD-ligand 1, anti-CD137 (urelumab), and anti-OX40. Biomarkers that can be used as predictive factors for these treatments have not yet been clinically validated. However, there is already evidence that the tumor microenvironment can have a predictive role, with clinical activity of ipilimumab related to high baseline expression of the immune-related genes FoxP3 and indoleamine 2,3-dioxygenase and an increase in tumor-infiltrating lymphocytes. These biomarkers could represent the first potential proposal for an immunoprofiling panel in patients for whom anti-CTLA-4 therapy is being considered, although prospective data are required. In conclusion, the evaluation of systemic and local immunological biomarkers could offer useful prognostic information and facilitate clinical decision making. The challenge will be to identify the individual immunoprofile of each patient and the consequent choice of optimal therapy or combination of therapies to be used.

Rosette-forming glioneuronal tumor of the cerebellum in statu nascendi: an incidentally detected diminutive example indicates derivation from the internal granule cell layer

Rosette-forming glioneuronal tumor (RGNT) is a recently introduced, indolent neoplasm composed of diminutive circular aggregates of neurocytic-like cells on a noninfiltrative astrocytic background, typically located in the cerebellar midline The traded concept of RGNT being derived from site-specific periventricular precursors may be questioned in the face of extracerebellar examples as well as ones occurring in combination with other representatives of the glioneuronal family. We describe a hitherto not documented example of asymptomatic RGNT discovered during autopsy of a 74-year-old male. Located in the tuberal vermis, this lesion of 6 mm diameter consisted of several microscopic nests of what were felt to represent nascent stages of RGNT, all of them centered on the internal granular layer, and ranging from mucoid dehiscences thereof to fully evolved - if small - tumor foci. Molecular genetic analysis revealed a missense mutation in Exon 20 of the PIK3CA gene involving an A→G transition at Nucleotide 3140. On the other hand, neither codeletion of chromosomes 1p/19q nor pathogenic mutations of IDH1/2 were detected. By analogy with in situ paradigms in other organs, we propose that this tumor is likely to have arisen from the internal granular layer, rather than the plate of the 4th ventricle. A suggestive departure from the wholesale argument of "undifferentiated precursors", this finding also indirectly indicates that a subset of non-classical RGNTs - in particular extracerebellar examples, whose origin cannot be mechanistically accounted for by either of the above structures - may possibly reflect an instance of phenotypic convergence, rather than a lineage-restricted entity.