Hydrothermisch behandelte Lupinen zur Eiweißversorgung der Milchkuh

According to producer statements hydrothermal treatment of lupines increases the amount of rumen undegradable protein (UDP) from 20 % to 45 % and nXP values from 196 to 245 g/kg thus providing sufficient protein for dairy cows. To evaluate the effects of hydrothermal treatment on nutritive value of lupines, intestinal protein supply and lactation performance as well as economical and ecological efficiency, a nine months feeding trial was carried out at the Agricultural Centre Haus Riswick, Kleve. Two groups of 20 cows blocked by milk yield, parity and expected calving date were fed a forage diet of grass-clover and corn silage enriched with 3 kg of concentrates (46 % blue lupine, 41 % triticale, 10 % wheat bran, 2 % mineral feed, 1 % rape oil), sufficient for 25 kg ECM (DLG, 2001). Nutrient values per kg dry matter were as follows (control/experiment): 6,8 / 6,8 MJ NEL, 168 / 168 g XP, 144 / 148 g nXP, 3,9 / 3,2 g RNB. Nutritive value of lupines was determined by feeding wethers according to standard procedure (GfE, 1991). Protein fractions were analysed according to Shannak et al. (2000). Experimental groups varied only in lupine treatment (Börde Kraftkorn, Gröningen, GER). Yield of natural and energy corrected milk (ECM), milk fat and milk protein were higher in cows fed treated lupines (p <0,001). Urea nitrogen concentration was marginally lower compared to controls (p <0,001). Improvement of lactational performance was slightly higher during the first 100 days of lactation, but persisted during the whole lactational period. Body weight and condition were not affected by treatment. Improved lactational performance resulted in an overall better economic result

Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia

Background: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies. Results: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m(2)/day with weekly dose escalations of 50 mg/m(2) until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m(2)/day was determined (maximum, 580 mg/m(2)/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C-max. Five patients achieved prolonged disease control (> 12 months) and showed a higher C-max (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. Conclusion: An SDR of 130 mg/m(2)/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker

Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size, and have limited clinical relevance. These concerns have prompted a paradigm shift towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Hence, we uniquely built/validated supervised neuroanatomical machine learning (ML) models for individual-level inferences, using the largest up to date neuroimaging database on youth anxiety disorders: ENIGMA Anxiety Consortium (N=3,343; Age: 10-25 years; Global Sites: 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (Panic Disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status, and symptom severity (AUC’s 0.59-0.63). Classifications were driven by neuroanatomical features (cortical thickness/surface area, subcortical volumes) in fronto-striato-limbic and temporo-parietal regions. This benchmark study provides estimates on individual-level classification performances that can be realistically achieved with ML using neuroanatomical data, within a large, heterogenous, and multi-site sample of youth with anxiety disorders

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

ACKNOWLEDGEMENTS

Germany under the supervision of Prof. Dr. Gerhard Winter. First and foremost, I would like to express my deepest gratitude to my supervisor Prof. Dr. Gerhard Winter, who gave me the opportunity to join his research group and to work in the fascinating field of protein pharmaceuticals. I want to thank him for his outstanding professional and enthusiastic guidance throughout this study and all the valuable advices that always encouraged and inspired me. I very much appreciated the numerous opportunities to present my work on congresses all over the world and the realization of my research stay in Colorado. I want to thank Prof. Dr. Wolfgang Frieß for his continuous enthusiasm and interest in my work, the scientific input and advice over the last years and for kindly being co-referee of this thesis. I would like to thank both of you, Prof. Winter and Prof. Frieß for the great efforts to provide excellent technical equipment and a pleasant working climate that made the development of this thesis not just possible, but a fulfilling and exciting time. I want to thank Dr. Sandra Schulze for her supervision and great support during the first months of this work. She excellently introduced me in the numerous analytical techniques and provided dedicated guidance at any time. I am indebted to Dr. Julia Myschik, who took over the supervision and was great help during preparation and performance of the animal studies. Many thanks to my cooperation partners from the University of Colorado: Prof. Dr. Theodore W. Randolph, Prof. Dr. John F. Carpenter and Maliheh Shomali for the cooperation and scientific input and thank you for the warm welcome during my research stay. Abbott GmbH &amp; Co. KG is gratefully acknowledged for scientific and financial support, providing materials and enabling the realization of animal studies in Ludwigshafen. I am deepl

Evaluation of Heat Flux Measurement as a New Process Analytical Technology Monitoring Tool in Freeze Drying

This study investigates the suitability of heat flux measurement as a new technique for monitoring product temperature and critical end points during freeze drying. The heat flux sensor is tightly mounted on the shelf and measures non-invasively (no contact with the product) the heat transferred from shelf to vial. Heat flux data were compared to comparative pressure measurement, thermocouple readings, and Karl Fischer titration as current state of the art monitoring techniques. The whole freeze drying process including freezing (both by ramp freezing and controlled nucleation) and primary and secondary drying was considered. We found that direct measurement of the transferred heat enables more insights into thermodynamics of the freezing process. Furthermore, a vial heat transfer coefficient can be calculated from heat flux data, which ultimately provides a non-invasive method to monitor product temperature throughout primary drying. The end point of primary drying determined by heat flux measurements was in accordance with the one defined by thermocouples. During secondary drying, heat flux measurements could not indicate the progress of drying as monitoring the residual moisture content. In conclusion, heat flux measurements are a promising new non-invasive tool for lyophilization process monitoring and development using energy transfer as a control parameter

Evaluation of a novel p-rated scale for selective mutism

Assessment of selective mutism (SM) is hampered by the lack of diagnostic measures. The Frankfurt Scale of Selective Mutism was developed for kindergarteners, schoolchildren, and adolescents, including the diagnostic scale (DS) and the severity scale (SS). The objective of this study was to evaluate this novel, parent-rated questionnaire among individuals aged 3 to 18 years (n = 334) with SM, social phobia, internalizing disorders, and a control group. Item analysis resulted in high item-total correlations, and internal consistency in both scales was excellent with Cronbach’s α = .90-.98. Exploratory factor analysis of the SS consistently yielded a one-factor solution. Mean sum scores of the DS differed significantly between the diagnostic groups, and the receiver operating characteristic analysis resulted in optimal cutoffs for distinguishing SM from all other groups with the area under the curves of 0.94-1.00. The SS sum scores correlated significantly with SM’s clinician-rated symptom severity