Language and Religion. Moroccan and Turkish Communities in Europe

In the 1960s labour migration from Morocco and Turkey to Western Europe started to take place. This labour migration was incited by the shortage of manpower in the European market. Initially these labourers had a shortterm goal in mind, to earn money and return to their countries of origin. This option of return soon changed into a myth. Spouses and children joined the working men and soon their children were born in Europe

p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer

Background: Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for long-time survival that can help to guide treatment decisions and might lead to the development of new therapies. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is the most frequently altered pathway in HNSCC, genes are often mutated, amplificated and overexpressed causing aberrant signaling affecting cell growth and differentiation. Numerous genetic alterations of upstream and downstream factors have currently been clarified. However, their predictive value has yet to be established. Therefore we assess the predictive value of p-mTOR, p-ERK and PTEN expression. Methods: Tissue microarrays (TMA’s) of HPV-negative patients with oropharyngeal (n = 48), hypopharyngeal (n = 16) or laryngeal (n = 13) SCC, treated with primary chemoradiation (cisplatin/carboplatin/cetuximab and radiotherapy), were histologically stained for p-mTOR, PTEN and p-ERK. Expression was correlated to overall survival (OS), disease free survival (DFS) and locoregional control (LRC). Also p-mTOR was histologically stained in a separate cohort of HNSCC organoids (n = 8) and correlated to mTOR-inhibitor everolimus response. Results: High p-mTOR expression correlated significantly with worse OS in multivariate analysis in the whole patient cohort [Hazar Ratio (HR) 1.06, 95%CI 1.01–1.11, p = 0.03] and in the cisplatin/carboplatin group with both worse OS (HR 1.09, 95%CI 1.02–1.16, p = 0.02) and DFS (HR 1.06, 95%CI 1.00–1.12, p = 0,04). p-ERK expression correlated significantly with DFS in univariate analysis in the whole patient cohort (HR 1.03, 95%CI 1.00–1.05, p = 0.04) and cisplatin/carboplatin group (HR 1.03, 95%CI 1.00–1.07, p = 0.04). PTEN-expression did not correlate with OS/DFS/LRC. Better organoid response to everolimus correlated significantly to higher p-mTOR expression (Rs = − 0.731, p = 0.04). Conclusions: High p-mTOR expression predicts and high p-ERK expression tends to predict worse treatment outcome in HPV negative HNSCC patients treated with chemoradiation, providing additional evidence that these markers are candidate prognostic biomarkers for survival in this patient population. Also this study shows that the use of HNSCC organoids for biomarker research has potential. The role of PTEN expression as prognostic biomarker remains unclear, as consistent evidence on its prognostic and predictive value is lacking.</p

Development and Function of Immune Cells in an Adolescent Patient with a Deficiency in the Interleukin-10 Receptor

OBJECTIVE:: Monogenic defects in the interleukin-10 (IL-10) pathway are extremely rare and cause infantile-onset inflammatory bowel disease (IBD)-like pathology. Understanding how immune responses are dysregulated in monogenic IBD-like diseases can provide valuable insight in “classical” IBD pathogenesis. Here, we studied long-term immune cell development and function in an adolescent IL-10 receptor (IL10RA)-deficient patient who presented in infancy with severe colitis and fistulizing perianal disease and is currently treated with immune suppressants. METHODS:: Biomaterial was collected from the IL10RA-deficient patient, pediatric IBD patients and healthy controls. The frequency and phenotype of immune cells were determined in peripheral blood and intestinal biopsies by flow cytometry and immunohistochemistry. Functional changes in monocyte-derived dendritic cells and T cells were assessed by in vitro activation assays. RESULTS:: The IL10RA-deficient immune system developed normally with respect to numbers and phenotype of circulating immune cells. Despite normal co-stimulatory molecule expression, bacterial lipopolysaccharide-stimulated monocyte-derived dendritic cells from the IL10RA-deficient patient released increased amounts of TNFα compared to healthy controls. Upon T-cell receptor ligation, IL10RA-deficient peripheral blood mononuclear cells released increased amounts of T cell cytokines IFNγ and IL-17 agreeing with high numbers of T-bet and IL-17 cells in intestinal biopsies taken at disease onset. In vitro, the immunosuppressive drug thalidomide used to treat the patient decreased peripheral blood mononuclear cell-derived TNFα production. CONCLUSIONS:: With time and during immunosuppressive treatment the IL10RA- deficient immune system develops relatively normally. Upon activation, IL-10 is crucial for controlling excessive inflammatory cytokine release by dendritic cells and preventing IFNγ and IL-17-mediated T-cell responses

First system for fully-automated multi-criterial treatment planning for a high-magnetic field MR-Linac applied to rectal cancer

Background and purpose: In this study we developed a workflow for fully-automated generation of deliverable IMRT plans for a 1.5 T MR-Linac (MRL) based on contoured CT scans, and we evaluated automated MRL planning for rectal cancer. Methods: The Monte Carlo dose calculation engine used in the clinical MRL TPS (Monaco, Elekta AB, Stockholm, Sweden), suited for high accuracy dose calculations in a 1.5 T magnetic field, was coupled to our in-house developed Erasmus-iCycle optimizer. Clinically deliverable plans for 23 rectal cancer patients were automatically generated in a two-step process, i.e., multi-criterial fluence map optimization with Erasmus-iCycle followed by a conversion into a deliverable IMRT plan in the clinical TPS. Automatically generated plans (AUTOplans) were compared to plans that were manually generated with the clinical TPS (MANplans). Results: With AUTOplanning large reductions in planning time and workload were obtained; 4–6 h mainly hands-on planning for MANplans vs 1 h of mainly computer computation time for AUTOplans. For equal target coverage, the bladder and bowel bag Dmean was reduced in the AUTOplans by 1.3 Gy (6.9%) on average with a maximum reduction of 4.5 Gy (23.8%). Dosimetric measurements at the MRL demonstrated clinically acceptable delivery accuracy for the AUTOplans. Conclusions: A system for fully automated multi-criterial planning for a 1.5 T MR-Linac was developed and tested for rectal cancer patients. Automated planning resulted in major reductions in planning workload and time, while plan quality improved. Negative impact of the high magnetic field on the dose distributions could be avoided