Fremdheitskonstruktion durch politische Entscheidungsprozesse - wer zugewandert ist, bleibt fremd!

Fremdheitskonstruktionen durch politische Entscheidungsprozesse – wer zugewandert ist, bleibt fremd! Ziele der Dissertation sind anhand der politischen Entscheidungsprozesse Green Card, Kopftuchdebatte, Zuwanderungsgesetz, Deutsche Islamkonferenz und dem Nationalen Integrationsgipfel in den Jahren 1998-2009, die Entscheidungsprozesse im politischen Zentrum und in der medialen Betrachtung inhaltlich zu analysieren. Eine zentrale These der Arbeit lautet, das nur über die konstante Behandlung und Sichtung der Diskurse in den Kontrollmedien Bild, FAZ, SZ, Taz und in den politischen Programmen, die Tragweite der Konstruktionen, ein Demokratiedefizit und die Schieflage im Diskurs zu Tage treten, die zu diesen Fremdheitskonstruktionen führen. Das theoretische Fundament bilden die Luhmannschen Überlegungen zum Mediendiskurs und eine Erweiterung des Schleusenmodells von Habermas/Peters hin zu einem Öffentlichkeitsmodell, um die komplexen Prozesse erfassen zu können, die politische Entscheidungsprozesse und den öffentlichen Diskurs darüber bestimmen

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Chronic severe somatoform disorder (SFD) is resistant to treatment. In a prospective observational study, we evaluated an intensive multidisciplinary treatment focusing on body-related mentalization and acceptance. Patients included in the study were 183 (146 women, 37 men) of 311 eligible patients with chronic severe SFD, referred consecutively to a specialized tertiary care center between 2002 and 2009. Primary outcome measures were somatic symptoms (SCL-90) and health-related quality of life (EuroQol 5-Dimensional [EQ-5D]). These measures were assessed four times before treatment (on intake, twice during an observation period, at start of treatment) and four times after treatment (during follow-up for 2 years). Multilevel analysis was used to separate effects of time (maturation) and treatment. Results revealed significant improvements in SCL-90 somatic symptoms (d = 0.51), EQ-5D index (d = 0.27), and EQ visual analogue scale (d = 0.56). Significant reductions were also observed in SCL-90 anxiety, depression, and overall psychopathology as well as in medical consumption associated with psychiatric illness (Trimbos/iMTA Questionnaire for Costs Associated With Psychiatric Illness). Large interindividual differences were found in treatment outcome. The long-term improvement seen in many patients suggests that intensive multidisciplinary tertiary care treatment is a useful approach to chronic severe SFD

Prospective Analysis in GIST Patients on the Role of Alpha-1 Acid Glycoprotein in Imatinib Exposure

Background: For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time. Methods: We prospectively measured imatinib trough concentration (Cmin) values in 28 patients with gastrointestinal stromal tumours, at 1, 3 and 12 months after the start of imatinib treatment. At the same time points, AGP levels were measured. Results: Overall, imatinib Cmin and AGP levels were correlated (r2 = 0.656; P < 0.001). However, AGP levels did not fluctuate significantly over time, nor did the change in AGP levels correlate with the change in the imatinib Cmin. Conclusion: We showed that systemic AGP levels are not likely to be a key player in the decrease in systemic imatinib exposure over time. As long as intra-individual changes in imatinib exposure remain unexplained, researchers should standardize the sampling times for imatinib in order to be able to assess the clinical applicability of therapeutic drug monitoring

Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancer

BACKGROUND: Cervical carcinoma develops as a result of multiple genetic alterations. Different studies investigated genomic alterations in cervical cancer mainly by means of metaphase comparative genomic hybridization (mCGH) and microsatellite marker analysis for the detection of loss of heterozygosity (LOH). Currently, high throughput methods such as array comparative genomic hybridization (array CGH), single nucleotide polymorphism array (SNP array) and gene expression arrays are available to study genome-wide alterations. Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression. RESULTS: Genome-wide copy number and genotype analysis of 10 cervical cancer cell lines by array CGH and SNP array showed highly complex large-scale alterations. A comparison between array CGH and SNP array revealed that the overall concordance in detection of the same areas with copy number alterations (CNA) was above 90%. The use of SNP arrays demonstrated that about 75% of LOH events would not have been found by methods which screen for copy number changes, such as array CGH, since these were LOH events without CNA. Regions frequently targeted by CNA, as determined by array CGH, such as amplification of 5p and 20q, and loss of 8p were confirmed by fluorescent in situ hybridization (FISH). Genome-wide, we did not find a correlation between copy-number and gene expression. At chromosome arm 5p however, 22% of the genes were significantly upregulated in cell lines with amplifications as compared to cell lines without amplifications, as measured by gene expression arrays. For 3 genes, SKP2, ANKH and TRIO, expression differences were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSION: This study showed that copy number data retrieved from either array CGH or SNP array are comparable and that the integration of genome-wide LOH, copy number and gene expression is useful for the identification of gene specific targets that could be relevant for the development and progression in cervical cancer

Visual classification of feral cat Felis silvestris catus vocalizations

Cat vocal behavior, in particular, the vocal and social behavior of feral cats, is poorly understood, as are the differences between feral and fully domestic cats. The relationship between feral cat social and vocal behavior is important because of the markedly different ecology of feral and domestic cats, and enhanced comprehension of the repertoire and potential information content of feral cat calls can provide both better understanding of the domestication and socialization process, and improved welfare for feral cats undergoing adoption. Previous studies have used conflicting classification schemes for cat vocalizations, often relying on onomatopoeic or popular descriptions of call types (e.g., “miow”). We studied the vocalizations of 13 unaltered domestic cats that complied with our behavioral definition used to distinguish feral cats from domestic. A total of 71 acoustic units were extracted and visually analyzed for the construction of a hierarchical classification of vocal sounds, based on acoustic properties. We identified 3 major categories (tonal, pulse, and broadband) that further breakdown into 8 subcategories, and show a high degree of reliability when sounds are classified blindly by independent observers (Fleiss’ Kappa $K$ = 0.863). Due to the limited behavioral contexts in this study, additional subcategories of cat vocalizations may be identified in the future, but our hierarchical classification system allows for the addition of new categories and new subcategories as they are described. This study shows that cat vocalizations are diverse and complex, and provides an objective and reliable classification system that can be used in future studies

Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: −0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD) n = 14) from those without osteoporosis (δ44/42CaBlood: −0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were − 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis

Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients

The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period). Tissue samples were used for mRNA expression analysis of drug-metabolizing enzymes. In patients, a cross-over study was performed. During three 24-h periods, after tamoxifen dosing at 8 a.m., 1 p.m., and 8 p.m., for at least 4 weeks, blood samples were collected for pharmacokinetic measurements. Differences in tamoxifen pharmacokinetics between administration times were assessed. The mRNA expression of drug-metabolizing enzymes showed circadian variation in mouse tissues. Tamoxifen exposure seemed to be highest after administration at midnight. In humans, marginal differences were observed in pharmacokinetic parameters between morning and evening administration. Tamoxifen Cmax and area under the curve (AUC)0–8 h were 20 % higher (P max was shorter (2.1 vs. 8.1 h; P = 0.001), indicating variation in absorption. Systemic exposure (AUC0–24 h) to endoxifen was 15 % higher (P < 0.001) following morning administration. The results suggest that dosing time is of marginal influence on tamoxifen pharmacokinetics. Our study was not designed to detect potential changes in clinical outcome or toxicity, based on a difference in the time of administration. Circadian rhythm may be one of the many determinants of the interpatient and intrapatient pharmacokinetic variability of tamoxifen

Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib’s inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential