Mesoskopisches Simulationsmodell zur Kollektivfortschreibung

Vorgestellt wird ein am ZPR neu entwickeltes Simulationsmodell zur Fortschreibung von Bausparkollektiven, das Verträge mit ähnlichem Sparverhalten in Gruppen zusammenfaßt und auf Einzelkonten basiert. Zum einen wird erläutert, wie mit Hilfe von Clusteranalyse Prototypen bestimmt werden, die das Sparverhalten der Schichten angeben, zum anderen wird gezeigt, wie anschließend ein gegebener Bestand an Bausparverträgen mittels eines Minimum-Cost-Flow-Algorithmus den definierten Schichten zugeordnet wird. Das beschriebene Modell eignet sich sowohl für kurz- als auch für langfristige Simulationen

Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA

BACKGROUND Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, 'SOFIA'. PATIENTS AND METHODS INCLUSION CRITERIA WERE: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m(2). In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics. RESULTS Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3-4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin. CONCLUSION Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Age estimation using vertebral bone spurs; Testing the efficacy of three methods on a European population

Age-at-death estimation is an essential step in both bioarchaeological and forensic studies when human remains are found, as this can also contribute to the identification of the individual. It is critical that age-at-death methods be tested verified in various populations, to obtain the most accurate estimation, making research into new age-at-death methods also imperative. Since osteophyte formation on the vertebral column increases with age, this can be used as a possible method of age-at-death estimation. Snodgrass (2004), Watanabe and Terazawa (2006) and Praneatpolgrang et al. (2019) have tested this method before and have provided promising results. We test the efficacy of Snodgrass (2004), Watanabe and Terazawa (2006), and Praneatpolgrang et al. (2019) on a 19th-century archivally recorded Dutch population. A total of 88 individuals, 40 males, and 48 females were scored for the degree of osteophyte formation on the vertebral column. In addition to testing the three methods above, population-specific regression equations were developed and tested. Accuracy percentages for estimating the age-at-death based on the mean osteophyte score of the entire vertebral column were obtained for all three methods (73.86%, 76.14%, and 72.73%, respectively). In this study, a general pattern of osteophyte formation could be established, which is useful for estimating the age at death. We therefore recommend that this method can be used, cautiously as a means of age-at-death estimation

Analyse großer Datenmengen und Clusteralgorithmen im Bausparwesen

Kollektivanalysen und darauf aufbauende Prognosen sind seit langem ein wichtiger Beitrag der Bausparmathematik zu Fragen der Liquiditätsplanung, der Produktpflege und der Produktentwicklung. Im Rahmen einer Kooperation zwischen den Landesbausparkassen und dem Zentrum für Paralleles Rechnen wurden daher Bausparmodelle entwickelt, die der Analyse des Verhaltens der Bausparer und der Vorhersage ihres zukünftigen Verhaltens dienen. Eine Weiterentwicklung dieser Modellansätze mit Hilfe der Clusteranalyse soll in diesem Beitrag vorgestellt werden

HER2 Dimerization Inhibitor Pertuzumab - Mode of Action and Clinical Data in Breast Cancer

The humanized monoclonal antibody pertuzumab prevents the dimerizationof HER2 with other HER receptors, in particular the pairing of the mostpotent signaling heterodimer HER2/HER3, thus providing a potent strategyfor dual HER2 inhibition. It binds to the extracellular domain of HER2at a different epitope than trastuzumab. Pertuzunnab and trastuzumab actin a complementary fashion and provide a more complete blockade ofHER2-mediated signal transduction than either agent alone. Phase IIstudies demonstrated that pertuzunnab was generally well tolerated as asingle agent or in combination with trastuzumab and/or cytotoxic agents,and implied an improved clinical efficacy of the combination ofpertuzumab and trastuzumab in early and advanced HER2-positive breastcancer. Results of the pivotal phase III study CLEOPATRA in patientswith HER2-positive metastatic breast cancer demonstrated that theaddition of pertuzumab to first-line combination therapy with docetaxeland trastuzumab significantly prolonged progression-free and overallsurvival without increasing cardiac toxicity. Currently, the combinationof both antibodies is being explored in the palliative setting as wellas in the treatment of early HER2-positive breast cancer. Dual HER2inhibition with the HER2 dimerization inhibitor pertuzumab andtrastuzumab may change clinical practice in HER2-positive first-linemetastatic breast cancer treatment