Of autoregressive continuous time model parameters estimation

This article revisits a sequential approach to the estimation of the parameter in a first-order autoregressive model (AR(1)) with continuous time. There is provided a numerical study to get a results of sequential estimations of the parameter in first-order autoregressive model with continuous time and is computed a stopping rule and the optimal time of observations. Also there is provided a comparing analysis of estimation results with using the sequential approach both the optimal time of observations

A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis

The quest for novel therapeutic targets in acute myeloid leukemia (AML) is still ongoing. One of such targets, cyclin A1, was shown to be overexpressed in AML including AML stem cells. However, the function of cyclin A1 in AML is largely unknown, and the data on its impact on patients´ survival remain controversial. Therefore, we developed a transgenic mouse model of stem cell-directed inducible cyclin A1 overexpression and crossed these mice with PML-RARα-knockin mice, which develop an AML M3-like phenotype. To observe the effects of cyclin A1 loss-of-function, we also crossed PML-RARα-knockin mice to cyclin A1-knockout mice. Neither overexpression nor loss of cyclin A1 significantly altered leukemogenesis in PML-RARα-knockin mice. These findings imply that upregulation of cyclin A1 is not essential for leukemogenesis. Our data suggest that cyclin A1 does not represent a suitable target for AML therapy

Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia

Neighbourhood greenness and income of occupants in four German areas: GINIplus and LISAplus

Objective We investigated whether families with lower individual-level socioeconomic status (SES) reside in less green neighbourhoods in four areas in Germany. Methods Data were collected within two German birth cohorts – GINIplus and LISAplus. Net equivalent household income was categorized into study area-specific tertiles and used as a proxy for individual-level SES. Neighbourhood greenness was calculated in 500-m buffers around home addresses as: 1) the mean normalized difference vegetation index (NDVI); 2) percent tree cover. Associations between income and neighbourhood greenness were assessed per study area using adjusted linear regression models. Results In the Munich and Leipzig areas, families in the low and medium income tertiles resided in neighbourhoods with lower NDVI compared to those in the high income tertile (mean percent change in NDVI: −4.0 (95% confidence interval = −6.7 to −1.3) and −5.5 (−10.9 to −0.2), respectively). In contrast, in the Wesel area, families in the low income tertile resided in neighbourhoods with higher NDVI (2.9 (0.5–5.3)). Only the association in the Munich area was replicated when using tree cover instead of the NDVI. Conclusions This study provides suggestive evidence that the presence and direction of associations between greenness and SES is region-specific in Germany. The degree of urbanization did not clarify this heterogeneity completely

Does the Constitution Provide More Ballot Access Protection for Presidential Elections Than for U.S. House Elections?

Both the U.S. Constitution and The Federalist Papers suggest that voters ought to have more freedom to vote for the candidate of their choice for the U.S. House of Representatives than they do for the President or the U.S. Senate. Yet, strangely, for the last thirty-three years, the U.S. Supreme Court and lower courts have ruled that the Constitution gives voters more freedom to vote for the candidate of their choice in presidential elections than in congressional elections. Also, state legislatures, which have been writing ballot access laws since 1888, have passed laws that make it easier for minor-party and independent candidates to get on the ballot for President than for the U.S. House. As a result, voters in virtually every state invariably have far more choices on their general election ballots for the President than they do for the House. This Article argues that the right of a voter to vote for someone other than a Democrat or a Republican for the House is just as important as a voter’s right to do so for President, and that courts should grant more ballot access protection to minor-party and independent candidates for the House

Physical Activity in German Adolescents Measured by Accelerometry and Activity Diary: Introducing a Comprehensive Approach for Data Management and Preliminary Results

INTRODUCTION: Surveillance of physical activity (PA) is increasingly based on accelerometry. However, data management guidelines are lacking. We propose an approach for combining accelerometry and diary based PA information for assessment of PA in adolescents and provide an example of this approach using data from German adolescents. METHODS: The 15-year-old participants comprised a subsample the GINIplus birth cohort (n = 328, 42.4% male). Data on PA was obtained from hip-worn accelerometers (ActiGraph GT3X) for seven consecutive days, combined with a prospective activity diary. Major aspects of data management were validity of wear time, handling of non-wear time and diary comments. After data cleaning, PA and percentage of adolescents meeting the recommendations for moderate-to-vigorous activity (MVPA) per day were determined. RESULTS: From the 2224 recorded days 493 days (25%) were invalid, mainly due to uncertainties relating to non-wear time (322 days). Ultimately, 269 of 328 subjects (82%) with valid data for at least three weekdays and one weekend day were included in the analysis. Mean MVPA per day was 39.1 minutes (SD ±25.0), with boys being more active than girls (41.8±21.5 minutes vs. 37.1±27.8 minutes, p<0.001). Accordingly, 24.7% of boys and 17.2% of girls (p<0.01) met the WHO recommendations for PA. School sport accounted for only 6% of weekly MVPA. In fact, most MVPA was performed during leisure time, with the majority of adolescents engaging in ball sports (25.4%) and endurance sports (19.7%). Girls also frequently reported dancing and gymnastics (23%). CONCLUSION: For assessment of PA in adolescents, collecting both accelerometry and diary-based information is recommended. The diary is vital for the identification of invalid data and non-compliant participants. Preliminary results suggest that four out of five German adolescents do not meet WHO recommendations for PA and that school sport contributes only little to MVPA

Assessing potential locations for flood-based farming using satellite imagery: a case study of Afar region, Ethiopia

The dry lowlands of Ethiopia are seasonally affected by long periods of low rainfall and, coinciding with rainfall in the Amhara highlands, flood waters which flow onto the lowlands resulting in damage to landscapes and settlements. In an attempt to convert water from storm generated floods into productive use, this study proposes a methodology using remote sensing data and geographical information system tools to identify potential sites where flood spreading weirs may be installed and farming systems developed which produce food and fodder for poor rural communities. First, land use land cover maps for the study area were developed using Landsat-8 and MODIS temporal data. Sentinel-1 data at 10 and 20m resolution on a 12-day basis were then used to determine flood prone areas. Slope and drainage maps were derived from Shuttle RADAR Topography Mission Digital Elevation Model at 90m spatial resolution. Accuracy assessment using ground survey data showed that overall accuracies (correctness) of the land use/land cover classes were 86% with kappa 0.82. Coinciding with rainfall in the uplands, March and April are the months with flood events in the short growing season (belg) and June, July and August have flood events during the major (meher) season. In the Afar region, there is potentially >0.55m ha land available for development using seasonal flood waters from belg or meher seasons. During the 4 years of monitoring (2015–2018), a minimum of 142,000 and 172,000 ha of land were flooded in the belg and meher seasons, respectively. The dominant flooded areas were found in slope classes of <2% with spatial coverage varying across the districts. We concluded that Afar has a huge potential for flood-based technology implementation and recommend further investigation into the investments needed to support new socio-economic opportunities and implications for the local agro-pastoral communities

Long-term follow-up of cytogenetically normal CEBPA-mutated AML

Background: The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations. Patients and methods: We investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up. Results: Median follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA mutations survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p = 0.008). Patients &lt;= 60 years and biCEBPA mutations showed a favorable prognosis with a 10-year OS rate of 81%. Both, bi- and moCEBPA-mutated groups had a low early death (d60) rate of 7% and 9%, respectively. Complete remission (CR) rates for biCEBPA and moCEBPA mutated patients were 82% vs. 70% (p = 0.17). biCEBPA mutated patients showed a longer relapse free survival (RFS) (median RFS 9.4 years vs. 1.5 years, p = 0.021) and a lower cumulative incidence of relapse (CIR) compared to moCEBPA-mutated patients. These differences in OS and RFS were confirmed after adjustment for known clinical and molecular prognostic factors. Conclusions: In this long-term observation we confirmed the favorable prognostic outcome of patients with biCEBPA mutations compared to moCEBPA-mutated CN-AML. The high probability of OS (81%) in younger patients is helpful to guide intensity of postremission therapy

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance

Perioperative Chemotherapy in Gastroesophageal Cancer. A Retrospective Monocenter Evaluation of 42 Cases

Background: Perioperative chemotherapy increases the overall and progression-free survival of patients suffering from resectable adenocarcinomas of the lower esophagus, gastroesophageal junction and stomach (GEC). Comparing different chemotherapy regimens platin-based protocols with 5-fluorouracil (5-FU)/calcium folinate (CF) or oral fluoropyrimidines were favorable in terms of efficacy and side-effects. However, there is no consensus which regimen is the most efficacious. Methods: 42 consecutive patients with resectable GEC (UICC II and III) were treated with 3 pre- and postoperative chemotherapy cycles each consisting of epirubicin, oxaliplatin and capecitabine (EOX). We analyzed the overall survival, progression-free survival and toxicity retrospectively in comparison to published data. Results: The median overall survival in our cohort was 29 months and the progression-free survival was 17 months. The most frequent grade 3 and 4 toxicities during preoperative chemotherapy were diarrhea (16.7%), leukocytopenia (9.5%) and nausea (9.5%); overall 38.1% of our patients suffered from grade 3 or 4 toxicity. Surgery was carried out in 83% of our patients, 69% of those achieved R0 resection. Conclusion: Comparing our data with the results of previously published randomized trials EOX is at least non-inferior with regard to overall survival, progression-free survival and toxicity. In conclusion, EOX is an appropriate perioperative therapy for patients with resectable GEC