2000 Philip C. Jessup

The State of Kuraca and the Republic of Senhava have submitted their differences concerning the vaccine trials to the International Court of Justice for resolution through a Special Agreement, in accordance with Article 40(1) of the Statute of the International Court of Justice

Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose vaginal challenge of non-human primates

International audienc

Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques

Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcc receptor (FccR)–mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FccR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.Fil: Moog, C. Institute of Virology. Strasbourg; FranciaFil: Dereuddre Bosquet, N. Universite Paris Sud; FranciaFil: Teillaud, J-L. Paris Descartes University; FranciaFil: Biedma, Marina Elizabeth. Institute of Virology. Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Holl, V. Hematology and Flow Department. Ginebra; SuizaFil: Van Ham, G. Universidad de Amberes; BélgicaFil: Heyndrickx, L. Universidad de Amberes; BélgicaFil: Van Dorsselaer, A. UMR 7178; FranciaFil: Katinger, D. Polymun Scientific GmbH; AlemaniaFil: Vcelar, B. Polymun Scientific GmbH; AlemaniaFil: Zolla Pazner, S. School of Medicine and New York Veterans Affairs Medical Center; Estados UnidosFil: Mangeot, I. Universite Paris Sud; FranciaFil: Kelly, C. King's College; Reino UnidoFil: Shattock, R. J.. Imperial College London; Reino UnidoFil: Le Grand, R. Universite Paris Sud; Franci

The early childhood development replication crisis, and how wearable technologies could help overcome it

Early Childhood Development (ECD) programs are currently understood as critical for children’s cognitive and socioemotional development, especially for those from disadvantaged backgrounds or most at risk for poor outcomes. Nevertheless, while the pioneering ECD programs evaluated in the literature have shown large and long-lasting impacts, replicating their successes has proven challenging in more recent years. We characterize this replication crisis and provide perspectives on how wearable technologies could help overcome it

A multi-institutional study of outcomes in stage I–III uterine carcinosarcoma

OBJECTIVE: To evaluate the use of adjuvant therapy after primary surgery for stage I–III uterine carcinosarcoma (CS). METHODS: A multi-institutional retrospective study of women with stage I–III CS was conducted. Analyses were stratified by stage (I/II and III). Patients were categorized according to adjuvant therapy: observation (OBS), radiation (RT), chemotherapy (CT) or multimodal therapy (CT + RT). Overall survival (OS) and progression-free survival (PFS) were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: 303 patients were identified across four institutions: 195 with stage I/II and 108 with stage III disease. In stage I/II disease, 75 (39.9%) received OBS, 33 (17.6%) CT, 37 (19.7%) RT, and 43 (22.9%) CT + RT. OBS was associated with a fourfold increased risk of death compared to CT (adjusted hazard ratio (aHR) = 4.48, p = 0.003). Patients receiving CT + RT had significantly improved PFS compared to those receiving CT alone (aHR = 0.43, p = 0.04), but no difference in OS. In the stage III cohort, 16 (15.0%) received OBS, 34 (31.8%) CT, 20 (18.7%) RT, and 37 (34.6%) CT + RT. OBS was associated with worse OS and PFS compared to CT (OS: aHR = 2.46, p = 0.04; PFS: aHR = 2.39, p = 0.03, respectively). A potential improvement in PFS was seen for those treated with CT + RT compared to CT alone, however it was not statistically significant (aHR = 0.53, p = 0.09). CONCLUSIONS: Observation after surgery was associated with poor outcomes in uterine CS compared to CT and RT alone. Multimodality therapy for women with stage I/II disease was associated with improved PFS compared to chemotherapy alone. Novel treatment options are needed to improve outcomes in this aggressive disease

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Contains fulltext : 118576.pdf (publisher's version ) (Open Access)Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes