Shadow Places: Patterns of Spatial Concentration and Incorporation of Irregular Immigrants in the Netherlands

Summary: In Western countries, irregular immigrants constitute a sizeable segment of the population. By combining quantitative and qualitative research methods, this article describes and explains irregular immigrants’ patterns of spatial concentration and incorporation in the Netherlands. So far these spatial patterns have not been described and explained systematically, neither in the Netherlands nor elsewhere. The article shows that illegal residence is selectively embedded in the (urban) social structure in various ways. The authors argue that irregular immigrants are likely to be spatially concentrated and incorporated in similar ways in other Western countries; now and in the foreseeable future

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Preadipocyte number in omental and subcutaneous adipose tissue of obese individuals

To determine the variation in preadipocyte isolation procedure and to assess the number and function of preadipocytes from subcutaneous and omental adipose tissue of obese individuals. The preadipocyte number per gram of adipose tissue in the abdominal-subcutaneous and abdominal-omental adipose stores of 27 obese subjects with a BMI of 44 +/- 10 kg/m(2) and an age of 40 +/- 9 years was determined. The assessment of the preadipocyte number was found to be labor intensive and error prone. Our data indicated that the number of stromal vascular cells (SVCs), isolated from the adipose tissue by collagenase digestion, was dependent on the duration of collagenase treatment and the size and the origin of the biopsy. In addition, the fat accumulation and leptin production by differentiated SVCs were dependent on the number of adherent SVCs (aSVCs) in the culture plate and the presence of proteins derived from serum and peroxisome proliferator-activated receptor ligands. Using our standardized isolation and differentiation protocol, we found that the number of SVCs, aSVCs, leptin production, and fat accumulation still varied considerably among individuals. Interestingly, within individuals, the number of SVCs, aSVCs, and the leptin production by differentiating aSVCs from both the subcutaneous and the omental fat depots were associated, whereas fat accumulation was not. In obese to severely obese subjects, differences in BMI and age could not explain differences in SVCs, aSVCs, leptin production, and fat accumulatio

Whole Exome Sequencing in Patients with the Cuticular Drusen Subtype of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous

Generation and Characterization of Anti–Citrullinated Protein Antibody–Producing B Cell Clones From Rheumatoid Arthritis Patients

Objective: Anti–citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). Aside from autoantibody production, the function of autoantigen-specific B cells remains poorly understood in the context of this disease. This study set out to elucidate autoantigen-specific B cell functions through the isolation and immortalization of unique citrullinated protein/peptide (CP)–reactive B cell clones from RA patients. Methods: B cell clones from either the blood or synovial fluid of cyclic citrullinated peptide 2 (CCP2) antibody–positive RA patients were immortalized by genetic reprogramming with Bcl-6 and Bcl-xL. Enzyme-linked immunosorbent assay and flow cytometry were used to identify CCP2-reactive clones and to further characterize surface marker and cytokine expression as well as B cell receptor signaling competence. Global gene expression profiles were interrogated by RNA sequencing. Results: Three unique CP-reactive memory B cell clones were generated from the blood or synovial fluid of 2 RA patients. CP-reactive memory B cells did not appear to be broadly cross-reactive, but rather had a fairly restricted epitope recognition profile. These clones were able to secrete both pro- and antiinflammatory cytokines and had a unique surface profile of costimulatory molecules and receptors, including CD40 and C5a receptor type 1, when compared to non-CP–reactive clones from the same patient. In addition, CP-reactive clones bound citrullinated protein, but not native protein, and could mobilize calcium in response to antigen binding. Conclusion: CP-reactive memory B cells comprise a rare, seemingly oligoclonal population with restricted epitope specificity and distinct phenotypic and molecular characteristics suggestive of antigen-presenting cells. Cloning by genetic reprogramming opens new avenues to study the function of autoreactive memory B cells, especially in terms of antigen processing, presentation, and subsequent T cell polarization

Private Equity funds and their performance in the post-crisis period

The work covers the topic of private equity funds performance and attempt to identify the impact of macroeconomic conditions on the entire industry. The recent central banks' actions put a question about the impact of changes in interest rates on the private equity funds performance. With the sample of 100 observations provided by Cambridge Associates, we identified the significant negative effect of prevailing low interest rates on the growth of private equity funds performance. We further attempt to answer the question, whether private equity funds operating in post-crisis years has on average higher growth rate, however, we could not provide the answer as we failed to reject the null, neutral effect hypothesis. Additionally, with a sample of 3092 observations provided by Bloomberg, we found that the effect of cheap debt has increased on average in the postcrisis period, predicting that the private equity performance can suffer once the interest rates rises enough

Pedigrees of six cuticular drusen (CD) families in which whole exome sequencing (WES) was performed.

<p>Circle and square symbols indicate female and male individuals, respectively. Symbols with slashes indicate deceased individuals. Black and empty symbols indicate affected and unaffected individuals, respectively. Asterisks indicate the family members for whom exome sequencing was performed. The numbers below the symbols indicate the age at participation of family members.</p

Rare missense variants identified in known macular degeneration genes in 12 sporadic CD subtype of AMD cases by WES.

<p>Rare missense variants identified in known macular degeneration genes in 12 sporadic CD subtype of AMD cases by WES.</p