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

Capacity building improve Malaysia's inspection and monitoring system for aquaculture and fishery products

The project aimed to help build a credible inspection and monitoring system that can guarantee safe quality products of Ministry of Health (MoH) and Department of Fisheries (DoF) by upgrading the analytical capacity of the laboratory staff directly involved in the analysis and detection of forbidden substances. Two training courses were implemented in 2011 in the Bio Security Centre in Kuantan, Malaysia. The first training course on 'Marine lipophilic toxins using LC-MS/MS has been implemented in June and the second training course on on Stilbenes and Nitroïmidazoles sample preparation and analysis with LC-MS/MS equipment was implemented in November, 2011. Through this knowledge transfer and laboratory enhancement the project contributed the laboratory's process towards getting accreditation under ISO 17025. The courses were implemented in partnership by Wageningen UR Institute of Food Safety (RIKILT) and Wageningen UR Centre for Development Innovation (CDI). Report no. CDI-12-00

RTEL1 contributes to DNA replication and repair and telomere maintenance

Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 is involved in DNA double-strand break repair. The role of mRtel1 in telomere maintenance and genome stability is poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine the function of mRtel1 in replication, DNA repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its role in replication and genome maintenance. Deletion of mRtel1 increased the frequency of sister chromatid exchange events and suppressed gene replacement, demonstrating the involvement of the protein in homologous recombination. mRtel1 localized transiently at telomeres and is needed for efficient telomere replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem cells appeared relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase. We propose that mRtel1 is a key protein for DNA replication, recombination, and repair and efficient elongation of telomeres by telomerase

Recidivism report 1997-2007. Trends in the reconviction rate of Dutch offenders

In the field of Dutch criminal law there is a comprehensive policy programme called ‘Working on Reduction of Recidivism’. Various measures are being implemented to help reduce the risk of prosecuted offenders relapsing into criminal behaviour. Some years ago, definite targets were formulated with respect to two offender groups. Between 2002 and 2010, the medium-term recidivism for both juvenile offenders sanctioned by court or PPS, and adult exprisoners will have to be reduced by 10 percentage points (VbbV, 2007). With regard to the latter group, the target was recently enhanced: by 2020, the reconviction rate of ex-prisoners must be reduced by 25 percent (MvJ, 2009). The Recidivism Monitor study constitutes a means of checking whether the realisation of the target figures holds a steady course. Each year, the WODC calculates the reconviction rate of Dutch offenders. Nearly all persons in the Netherlands who came into contact with the Dutch judicial system as a suspect are included in the study. The measurements relate to five populations: adult offenders sanctioned by court or Public Prosecutor’s Service (PPS), juvenile offenders sanctioned by court or PPS, ex-prisoners, former inmates of juvenile detention centres and former offenders placed under an entrustment order. Recently, the relapse among former offenders placed under an entrustment order was reported separately (Bregman & Wartna, 2010). This fact sheet outlines recidivism in the other four offender populations. Specifically, the study relates to juveniles and adults who were sanctioned by court or PPS or released from a penitentiary institution in the 1997-2007 period

Model-Based Selection for Proton Therapy in Breast Cancer:Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences

Aims: Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences. Materials and methods: A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy. Results: The model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021. Conclusion: The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands

IFNα-mediated remodeling of endothelial cells in the bone marrow niche

In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha induces rapid cell cycle entry of hematopoietic stem cells in vivo. However, the effect of interferon alpha on bone marrow endothelial cells has not been described. Here, we demonstrate that acute interferon alpha treatment leads to rapid stimulation of bone marrow endothelial cells in vivo, resulting in increased bone marrow vascularity and vascular leakage. We find that activation of bone marrow endothelial cells involves the expression of key inflammatory and endothelial cell-stimulatory markers. This interferon alpha-mediated activation of bone marrow endothelial cells is dependent in part on vascular endothelial growth factor signaling in bone marrow hematopoietic cell types, including hematopoietic stem cells. Thus, this implies a role for hematopoietic stem cells in remodeling of the bone marrow niche in vivo following inflammatory stress. These data increase our current understanding of the relationship between hematopoietic stem cells and the bone marrow niche under inflammatory stress and also clarify the response of bone marrow niche endothelial cells to acute interferon alpha treatment in vivo

Recidivism report 2002-2008. Trends in the reconviction rate of Dutch offenders

Policy programmes in the field of Dutch criminal law often aim at the reduction of recidivism; measures are taken to lower the risk of prosecuted offenders relapsing into criminal behaviour. Some years ago, specific targets were formulated with respect to two major offender groups. For convicted juvenile offenders, and for adult ex-prisoners, the medium-term recidivism will have to be reduced by 10 percentage points between 2002 and 2010 (VbbV, 2007). The current government also endorses the need to suppress recidivism (DSP, 2011). A substantial part of crime in the Netherlands is committed by persons who have been prosecuted before. Therefore, crime prevention is also the prevention of recidivism. The Recidivism Monitor is an ongoing research project carried out by the WODC. With this instrument the realisation of the recidivism targets can be monitored. Each year, the WODC reports on the reconviction rate of Dutch offenders. Nearly all persons who were suspect in a penal case are included in the study. The standard measurements of the Recidivism Monitor relate to five offender populations: adult offenders sanctioned by court or Public Prosecutor’s Service (PPS), juvenile offenders sanctioned by court or PPS, ex-prisoners, former inmates of juvenile detention centres and former offenders placed under an entrustment order (tbs).1 The reconviction rates in the tbs-sector are reported on separately (see int. al. Bregman & Wartna, 2011). This fact sheet outlines known recidivism in the other four offender populations. Specifically, the study relates to juveniles and adults who were sanctioned by court or PPS or released from a penitentiary institution in the years between 2002, the first year of the target period, and 2008, the latest year for which statistics are currently available

Identification of DNA methylation changes at cis-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important cis-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set : translation and cross-cultural adaptation into 15 languages

Introduction: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. Discussion: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures