Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees

In humans, clearance of hepatitis C virus (HCV) infection is associated with genetic variation near the IL-28B gene and the induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To study whether similar correlations exist in these animals, a direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed. All chimpanzees studied were monomorphic for the human IL-28B SNPs which are associated with spontaneous and treatment induced HCV clearance in humans. As a result, these particular SNPs cannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated with HCV-RNA load and γGT, while such correlations were not observed in humans. The correlation between IP-10, γGT and virus load in chimpanzees was not found in patients and may be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are important during HCV infection in both species. The Genbank EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B gene are HE599784 and HE599785

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Perspectivas de reajuste industrial: la Comunidad Económica Europea y los países en desarrollo

Incluye Bibliografí

Validatie van grondwaterstandsinformatie over verdroging : Fase 2: opzet en inrichting van een validatiemeetnet in het pilotgebied Boetelerveld

In het natuurgebied Boetelerveld is middels een kanssteekproef een validatiemeetnet ingericht waarmee de kwaliteit van gebiedsdekkende grondwaterstandinformatie kan worden vastgesteld. In dit validatiemeetnet is gedurende één jaar en zeven maanden op tien locaties viermaal daags de grondwaterstand gemeten met automatische drukopnemers, in één tot drie filters op verschillende diepten. Het doel van de metingen was om het validatiemeetnet in de praktijk te toetsen

Waterretentie en doorlatendheidskarakteristieken in met klei verrijkte zandgrond

Water retention and hydraulic conductivity of soils are dependent on texture and structure. In case clay ismixed in a sandy top soil this will change its texture and structure. In this study the water retention andhydraulic conductivity characteristics are determined for samples with clay mixed in sand and compared tothose for sand