Proteomic study of proteolysis during ripening of cheddar cheese made from milk over a lactation cycle

Milk for cheese production in Ireland is predominantly produced by pasture-fed spring-calving herds. Consequently, there are marked seasonal changes in milk composition, which arise from the interactive lactational, dietary and environmental factors. In this study, Cheddar cheese was manufactured on a laboratory scale from milk taken from a spring calving herd, over a 9-month lactation cycle between early April and early December. Plasmin activity of 6-months-old Cheddar cheese samples generally decreased over ripening time. One-dimensional urea-polyacrylamide gel electrophoresis (PAGE) of cheese samples taken after 6 months of ripening showed an extensive hydrolysis of caseins, with the fastest hydrolysis of αs1-caseins in cheeses made in August. A proteomic comparison between cheeses produced from milk taken in April, August and December showed a reduction in levels of β-casein and appearance of additional products, corresponding to low molecular weight hydrolysis products of the caseins. This study has demonstrated that a seasonal milk supply causes compositional differences in Cheddar cheese, and that proteomic tools are helpful in understanding the impact of those differences

Longitudinal Analysis of Circulating Tumor Cells in Colorectal Cancer Patients by a Cytological and Molecular Approach: Feasibility and Clinical Application

Introduction Liquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics. Methods In total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE® cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters. Results Detection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE® method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE® for CTC detection. Conclusion Our study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine

Efficacy and toxicity of bimodal radiotherapy in WHO grade 2 meningiomas following subtotal resection with carbon ion boost:Prospective phase 2 MARCIE trial

Background: Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5).Methods:A total of 33 patients were enrolled from July 2012 until July 2020. The study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). The primary endpoint was the 3-year progression-free survival (PFS), and the secondary endpoints included overall survival, safety and treatment toxicities. Results:With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7%, and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in 1 patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients. Conclusions:Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve a superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.</p

Rehabilitative Versorgung und gesundheitsbedingte Frühberentung von Personen mit Migrationshintergrund in Deutschland: Abschlussbericht

Dieser Abschlussbericht stellt die Ergebnisse des Projektes "Rehabilitative Versorgung und gesundheitsbedingte Frühberentung von Personen mit Migrationshintergrund in Deutschland" vor. Auf Basis eines quantitativen und qualitativen Forschungszugangs wurde untersucht, inwiefern sich einzelne Gruppen von ausländischen Staatsangehörigen bzw. Menschen mit Migrationshintergrund hinsichtlich der Häufigkeit von Arbeitsunfällen und Berufskrankheiten, der Inanspruchnahme beruflicher und medizinischer Rehabilitationsmaßnahmen, des Rehabilitationserfolges und der Frühberentung von Deutschen bzw. Menschen ohne Migrationshintergrund unterscheiden. Unter Bezugnahme auf Prozess- und Individualdaten unterschiedlicher Rehabilitationsträger zeigt der Bericht, dass Menschen mit Migrationshintergrund im Durchschnitt weniger häufig Maßnahmen der medizinischen Rehabilitation in Anspruch nehmen sowie einen geringeren Rehabilitationserfolg und höhere Frühberentungsquoten aufweisen als die Mehrheitsbevölkerung. Auf Basis einer systematischen Literaturrecherche und mittels qualitativer Experten- und Fokusgruppeninterviews werden darüber hinaus unterschiedliche Zugangs-, Durchführungs- und Wirksamkeitsbarrieren in der Rehabilitation von Menschen mit Migrationshintergrund identifiziert, welche die quantitativen Ergebnisse zumindest teilweise erklären können. Handlungsempfehlungen für die Verbesserung der rehabilitativen Versorgung von Menschen mit Migrationshintergrund werden abgeleitet

The Dualism of Contemporary Traditional Governance and the State

In many parts of the world, people live in “dual polities”: they are governed by the state and organize collective decision making within their ethnic community according to traditional rules. We examine the substantial body of works on the traditional–state dualism, focusing on the internal organization of traditional polities, their interaction with the state, and the political consequences of the dualism. We find the descriptions of the internal organization of traditional polities scattered and lacking comparative perspective. The literature on the interaction provides a good starting point for theorizing the strategic role of traditional leaders as intermediaries, but large potentials for inference remain underexploited. Studies on the consequences of “dual polities” for democracy, conflict, and development are promising in their explanatory endeavor, but they do not yet allow for robust conclusions. We therefore propose an institutionalist research agenda addressing the need for theory and for systematic data collection and explanatory approaches

Število premikov največje ploščice na najkrajših poteh v hanojskih grafih

In contrast to the widespread interest in the Frame-Stewart conjecture (FSC) about the optimal number of moves in the classical Tower of Hanoi task with more than three pegs, this is the first study of the question of investigating shortest paths in Hanoi graphs ▫$H_p^n$▫ in a more general setting. Here ▫$p$▫ stands for the number of pegs and ▫$n$▫ for the number of discs in the Tower of Hanoi interpretation of these graphs. The analysis depends crucially on the number of largest disc moves (LDMs). The patterns of these LDMs will be coded as binary strings of length ▫$p-1$▫ assigned to each pair of starting and goal states individually. This will be approached both analytically and numerically. The main theoretical achievement is the existence, at least for all ▫$n geqslant p(p-2)$▫, of optimal paths where ▫$p-1$▫ LDMs are necessary. Numerical results, obtained by an algorithm based on a modified breadth-first search making use of symmetries of the graphs, lead to a couple of conjectures about some cases not covered by our ascertained results. These, in turn, may shed some light on the notoriously open FSC.Kljub širšemu zanimanju za Frame-Stewartovo domnevo o optimalnem številu potez v klasičnem problemu hanojskega stolpa z več kot tremi položaji, je to prva študija o najkrajših poteh v hanojskih grafih ▫$H_p^n$▫, kjer ▫$p$▫ predstavlja število položajev in ▫$n$▫ število ploščic, če graf interpretiramo kot graf stanj hanojskega stolpa. Študija se še posebej loti analize premikov največje ploščice. Vzorec teh premikov je zakodiran kot binarni niz dolžine ▫$p-1$▫ in prirejen vsakemu paru začetnega in končnega stanja posebej. K analizi problema se pristopa tako analitično kot tudi numerično. Glavni teoretični dosežek je obstoj optimalnih poti za vse ▫$n geqslant p(p-2)$▫, na katerih so nujni ▫$p-1$▫ premiki največje ploščice. Numerični rezultati so pridobljeni z modificiranim algoritmom, zasnovanim na algoritmu iskanja v širino. V namene optimizacije iskanja se uporabijo simetrije grafov. Numerična evidenca vodi k nekaj domnevam o (ne)obstoju, ki jih teoretični rezultati ne pokrivajo in mogoče nam pomaga razkriti tudi kakšno skrivnost še nerazrešene Frame-Stewartove domneve

Bildung und Lebenszufriedenheit : Ergebnisse der Konstanzer Bürgerbefragung ; 2011 - 4. Welle

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Sample-based longitudinal discrete choice experiments: preferences for electric vehicles over time

Discrete choice experiments have emerged as the state-of-the-art method for measuring preferences, but they are mostly used in cross-sectional studies. In seeking to make them applicable for longitudinal studies, our study addresses two common challenges: working with different respondents and handling altering attributes. We propose a sample-based longitudinal discrete choice experiment in combination with a covariate-extended hierarchical Bayes logit estimator that allows one to test the statistical significance of changes. We showcase this method’s use in studies about preferences for electric vehicles over six years and empirically observe that preferences develop in an unpredictable, non-monotonous way. We also find that inspecting only the absolute differences in preferences between samples may result in misleading inferences. Moreover, surveying a new sample produced similar results as asking the same sample of respondents over time. Finally, we experimentally test how adding or removing an attribute affects preferences for the other attributes