Mapping and analysis of types of migration from CEE countries. Country Report the Netherlands

Introduction The objective of this country report about the Netherlands is to describe the size and nature of migration from Central and Eastern European (CEE) countries to the Netherlands (chapter 2), to identify two urban regions and six separate municipalities within these regions as research locations for this study and to collect available information about CEE migrants in these regions (chapter 3) and, finally, to identify the most relevant types of CEE migrants in the Netherlands (chapter 4). We will start, however, with a discussion of the available data sources and research about CEE migrants in the Netherlands. In general, there are three different sources of information about CEE migrants in the Netherlands

Lack of uniform diagnostic criteria for cervical radiculopathy in conservative intervention studies: A systematic review

Purpose: Cervical radiculopathy (CR) is a common diagnosis. It is unclear if intervention studies use uniform definitions and criteria for patient selection. Our objective was to assess the uniformity of diagnostic criteria and definitions used in intervention studies to select patients with CR. Methods: We electronically searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL. Studies were included when evaluating conservative interventions in randomised clinical trials (RCTs) in patients with CR. Selection criteria and definitions for patients with CR were extracted and evaluated on their uniformity. Results: Thirteen RCTs were included. Pain was used as an inclusion criterion in 11 studies. Inclusion based on the duration and location of pain varied between studies. Five studies used sensory symptoms in the arm as inclusion crite

AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients

AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients.BackgroundTacrolimus has a narrow therapeutic window, and bioavailability is known to vary considerably between renal transplant recipients. Most centers still rely on measurement of trough levels, but there are conflicting reports on the correlation between tacrolimus trough levels and systemic exposure, as measured by the area-under-the-concentration-over-time curve (AUC(0-12h)).MethodsWe developed and validated a two-compartmental population-based pharmacokinetic model with Bayesian estimation of tacrolimus systemic exposure. Subsequently, we used this model to apply prospectively AUC-guided dosing of tacrolimus in 15 consecutive renal transplant recipients. The main objective was to study intrapatient variability in the course of time.ResultsBayesian forecasting with a two-point sampling strategy, a trough level, and a second sample obtained between two and four hours post-dose significantly improved the squared correlation with the AUC(0-12h) (r2= 0.94). Compared with trough level monitoring only, this approach reduced the 95%-prediction interval by 50%. The Bayesian approach proved to be feasible in clinical practice, and provided accurate information about systemic tacrolimus exposure in individual patients. In the AUC-guided dosing cohort the apparent clearance of tacrolimus decreased gradually over time, which was not reflected in corresponding trough levels.ConclusionThis simple, flexible method provides the opportunity to tailor immunosuppression, and should help minimize tacrolimus-related toxicity, such as nephrotoxicity and post-transplant diabetes mellitus

Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer

<p>Abstract</p> <p>Background</p> <p>Infection with high risk Human Papilloma Virus (HPV) is associated with cancer of the cervix, vagina, penis, vulva, anus and some cases of head and neck carcinomas. The HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore potential targets for T cell mediated adoptive immunotherapy. Effective immunotherapy is dependent on the presence of both CD4+ and CD8+ T cells. However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer.</p> <p>Methods</p> <p>HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively) directed against HPV16 antigens. Functional analysis was performed by interferon-γ secretion, proliferation and cytokine production assays.</p> <p>Results</p> <p>Introduction of HPV16 specific TCRs into blood derived CD4+ recipient T cells resulted in recognition of the relevant HPV16 epitope as determined by IFN-γ secretion. Importantly, we also show recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented HPV16E7 epitope by A9 TCR transgenic CD4+ T cells.</p> <p>Conclusion</p> <p>Our data indicate that TCR transfer is feasible as an alternative strategy to generate human HPV16 specific CD4+ T helper cells for the treatment of patients suffering from cervical cancer and other HPV16 induced malignancies.</p

Designing forest biodiversity experiments : general considerations illustrated by a new large experiment in subtropical China

Funded by German Research Foundation. Grant Number: DFG FOR 891/1 and 2 National Natural Science Foundation of China. Grant Numbers: NSFC 30710103907, 30930005, 31170457 , 31210103910 Swiss National Science Foundation (SNSF) Sino-German Centre for Research Promotion in BeijingPeer reviewedPublisher PD