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- Fakultät für Angewandte Gesundheits- und Sozialwissenschaften (414) (remove)
Wie wird Vaterschaft ermittelt? Das Bundesverfassungsgerichtsurteil zu so genannten heimlichen Vaterschaftstests hat einen Anspruch auf die genetische Abstammungsklärung verankert. Ziel dieser Klärung ist es für Väter, festzustellen, ob ihr rechtliches Kind auch ihr biologisches Kind ist. Dem Urteil folgte ein Gesetz zur Klärung der Abstammung. Das neue Gesetz schafft den „stets sicheren“ Vater. Wie ist es vor diesem Hintergrund um die Sicherheit des Kindes bestellt? In welchem Verhältnis stehen Vaterrechte und Kinderrechte? Diesen Fragen geht Sabina Schutter anhand eines diskursanalytischen Verfahrens nach.
Your one-stop solution for getting up and running with SQL Server 2000
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Setup, manage, and customize SQL Server 2000
Administer multiple instances of SQL Server 2000 using the SQL Server Enterprise Manager
Perform simple and complex database queries
Tune the performance of your SELECT statements
Use SQL extensions, stored procedures, transactions, views, and triggers
Implement the SQL Server 2000 security model
Find and fix database problems by capturing and replaying server activity
Import, export, and transform data types using DTS
Construct data warehouses to collect, organize, and distribute information efficiently
Background
To date, targeted tyrosine kinase inhibitors have been approved for FGFR2 and FGFR3 fusions (pemigatinib and erdafitinib, respectively), but the importance of FGFR2 mutations for transformation activity and as a druggable gene variant with response to different FGFR inhibitors is poorly understood. FGFR2 inhibitors present a mainstay of treatment for locally advanced or metastatic intrahepatic cholangiocellular carcinoma (iCCA).
Methods
A 74-year-old male was diagnosed with iCCA in liver segments seven and eight with infiltration of the hepatic veins and inferior vena cava revealed a C382R mutation of the intramembrane domain of FGRR2 receptor. We performed an in-silico study to understand the potential mode-of-action of the mutant FGFR2 targets. Based on experimentally determined structures we then used a structure generated by AlphaFold2 as the variation in question is located at a position not determined well in the experiments. This revealed that the C382R mutation is located in the trans-membranal domain at a position crucial for signal transduction, both for activation and inhibition of downstream-signaling. The Molecular Tumor Board decided to start the treatment with 13.5 mg pemigatinib once daily for 14 days, followed by 7 days of free therapy interval resulting in a sustained partial response. The patient continues to be treated of 13.5 mg as described above.
Results
In our case report, we were able to show that the patient in whom an C382R mutation was detected responded to the therapy with pemigatinib. This shows that real-world scenarios differ from the data of the approval studies, thereby illustrating how complex data on patients with FGFR mutations is. One of the main problems of large approval studies is that the functionality of the respective alterations is often disregarded.
Conclusions
Our results suggest that respective mutation may be successfully targeted by FGFR-selective tyrosine-kinase inhibitors, demonstrating the importance of the functional characterization of mutations.
no conflicts of interest.
Objective. The authors performed a methodological comparison of the usual standard gamble with methods that could also be used in mailed questionnaires.Methods.Ninety-two diabetic patients valued diabetes-related health states twice. In face-to-face interviews, the authors used an iterative standard gamble (ISG) in which the probabilities were varied in a ping-pong manner and a self-completion method (SC) with top-down titration as search procedure (SC-TD) in 2 independent subsamples of 46 patients. Three months later, all patients received a mailed questionnaire in which the authors used the self-completion method with bottom-up (SCBU) and SC-TD as search procedures.Results.ISG and SCTD showed feasibility and consistency in the interviews. The ISG resulted in significantly higher utilities than the SC-TD. Two thirds of the mailed questionnaires provided useful results indicating some problems of feasibility. Utilities measured by SC-BU and SC-TD did not differ significantly showing procedural invariance. Further, patients indicated ambivalence when given the choice not to definitely state their preferences.Conclusions.The results show that different strategies to collect standard gamble utilities can yield different results. Compared with the usually applied ISG, the SC method is feasible in interviews and provides a consistent alternative that is less costly when used in mailed questionnaires, although its practicability has to be improved in this later setting.
Purpose: This study aimed to gain knowledge about environmental factors (EFs) that impact work and social life participation of people with multiple sclerosis (MS) in Austria and Switzerland to extend the knowledge of participation and to identify key areas for measuring participation.
Method: A three-round Delphi study was conducted defining patients as experts. In the 1st round, qualitative data was gathered through questionnaires, analyzed with content analysis, and factors were assigned to EFs as classified in the ICF. In the 2nd and 3rd round, experts judged EFs according to its relevance to obtain consensus (cut-off 75%). Categories were ranked on a scale from mostly important to important.
Results: One hundred and twelve Austrian and 109 Swiss experts were recruited. The content analysis revealed 768 EFs. The study resulted in a list of 176 consensus factors for Austria and 177 Switzerland. Five categories revealed to be highly important, 12 moderately important, 6 fairly important, and 10 important.
Conclusions: This study indicates that participation in work or social life is influenced by physical, social, attitudinal, and policy factors. Consensus factors afford insights into areas for consideration in the development of participation outcome measurements and support a comprehensive and inclusive rehabilitation approach.
Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation.
Predictive Modeling (PM) techniques are gaining importance in the worldwide health insurance business. Modern PM methods are used for customer relationship management, risk evaluation or medical management. This article illustrates a PM approach that enables the economic potential of (cost-)effective disease management programs (DMPs) to be fully exploited by optimized candidate selection as an example of successful data-driven business management. The approach is based on a Generalized Linear Model (GLM) that is easy to apply for health insurance companies. By means of a small portfolio from an emerging country, we show that our GLM approach is stable compared to more sophisticated regression techniques in spite of the difficult data environment. Additionally, we demonstrate for this example of a setting that our model can compete with the expensive solutions offered by professional PM vendors and outperforms non-predictive standard approaches for DMP selection commonly used in the market.
The International Spinal Cord Injury (InSCI) community survey has been developed to collect internationally comparable data on the lived experience of persons with spinal cord injury (SCI) in all 6 WHO regions.
The InSCI survey provides a crucial first step to generate evidence on functioning, health maintenance, and subjective well-being in persons with SCI globally.
A major challenge in setting up the InSCI community survey was to develop a data model and questionnaire that comprehensively captures what matters to people and, at the same time, is feasible and parsimonious in terms of participant’s burden.
This paper outlines the components of the InSCI data model and presents the question selection to operationalize the data model along the 4 guiding principles of efficiency, feasibility, comparability, and truth and discrimination.
The data model consists of 6 components operationalized with 125 questions including functioning (n = 28 body functions and structures; n = 42 activities and participation), contextual factors (n = 26 environmental; n = 19 personal factors), lesion characteristics (n = 2), and appraisal of health and well-being (n = 8).
The InSCI questionnaire presents an efficient and feasible solution with satisfying comparability to other populations; however, its validity and reliability still needs to be confirmed.
For cost–benefit analysis, health technologies with multiple effects should be valued in a single scenario by a holistic willingness‐to‐pay (WTP) measure. Recent studies instead used decomposed scenarios in which respondents report their WTP for each individual effect. Evidence can be found that the sum of such decomposed WTPs overestimates the holistic WTP, i.e. the holistic WTP is sub‐additive. This sum of decomposed WTPs can lead to wrong conclusions on the efficiency of health technologies. This is also relevant in decision making about new technologies that are valued separately in different surveys. To date, no utility‐theoretical and empirically validated aggregation function for decomposed WTPs exists. Within an expected utility model, this paper identifies as a reason for sub‐additivity – beside risk aversion with respect to wealth – a negative influence of better health on the marginal utility of wealth, i.e. marginal utility of wealth is smaller in better health states. Assuming mutual utility independence of health and wealth, a theoretically founded aggregation function covering these two impacts is derived. In a contingent valuation study, 92 patients with diabetes were asked to state their WTP for reductions of the risk of several diabetic complications in decomposed as well as in holistic scenarios. The patients had preferences with a significant negative influence of health on the marginal utility of wealth. Sub‐additivity occurred and theoretically founded aggregation could considerably lower the degree of overestimation. These results suggest that the theoretically founded aggregation function might reduce problems of sub‐additivity that can be economically relevant. Further empirical testing of the approach is indicated.