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BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall s
BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.METHODS: 2,116 familial melanoma cases were ascertained by the inte
Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantita
In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation, and pathology as well as parasite–parasite communication. In this report, we summarised the role of EVs in inf
Investigating the chemical homogeneity of stars born from the same molecular cloud at virtually the same time is very important for our understanding of the chemical enrichment of the interstellar medium and with it the chemical evolution of the Galaxy. One major cause of inhomogeneities in the abundances of open clusters is stellar evolution of the cluster members. In this work, we investigate va
Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and in
BACKGROUND: Clinical outcome of patients with triple-negative breast cancer (TNBC) is highly variable. This study aims to identify and validate a prognostic protein signature for TNBC patients to reduce unnecessary adjuvant systemic therapy.METHODS: Frozen primary tumors were collected from 126 lymph node-negative and adjuvant therapy-naive TNBC patients. These samples were used for global proteom
BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.METHODS: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority t
BACKGROUND: Plasma biomarkers associated with Alzheimer's disease could improve prognostic assessment for people with Down syndrome in both clinical practice and research settings. We aimed to identify the plasma biomarkers that most accurately predict longitudinal changes in Alzheimer's disease-related pathology and cognitive functioning in individuals with Down syndrome.METHODS: This longitudina
In pancreatic ductal adenocarcinoma (PDAC), the dense desmoplastic stroma and insufficient infiltrating T cells represent a significant barrier to effective immunotherapy. In this phase I, dose-escalation study, previously registered at the Dutch Trial Register and later on at ClinicalTrial (NCT05650918), we administer an autologous dendritic cell (DC) vaccine (MesoPher) with an agonistic CD40-spe
Background: Platelet transfusions are given to preterm infants with severe thrombocytopenia aiming to prevent haemorrhage. The PlaNeT2/MATISSE trial revealed higher rates of mortality and/or major bleeding in preterm infants receiving prophylactic platelet transfusions at a platelet count threshold of 50 × 109/L compared to 25 × 109/L. The extent to which this evidence has been incorporated into c
BACKGROUND: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort.METHODS: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseli
BACKGROUND: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pedia
Purpose: Humoral immunity proteins—immunoglobulins, complement proteins, and antimicrobial peptides—have key antimicrobial and immunomodulatory functions in sepsis. We hypothesised that their circulating levels are lower in non-survivors, potentially resulting in impaired bacterial clearance and persistent or recurrent infections. Methods: We performed a systematic review and meta-analysis evaluat
Rhesus macaques (RMs) are a vital model for studying human disease and are invaluable to preclinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To
We present a detailed analysis of HARPS-N radial velocity observations of K2-100, a young and active star in the Praesepe cluster, which hosts a transiting planet with a period of 1.7 d. We model the activity-induced radial velocity variations of the host star with a multidimensional Gaussian Process framework and detect a planetary signal of 10.6 ± 3.0 m s−1, which matches the transit ephemeris,
We present the discovery and confirmation of two new transiting giant planets from the Kepler extended mission K2. K2-260 b is a hot Jupiter transiting a V = 12.7 F6V star in K2 Field 13, with a mass and radius of M = 1.39-0.06+0.05 M⊙ and R = 1.69 ± 0.03 R. The planet has an orbital period of P = 2.627 d, and a mass and radius of MP = 1.42-0.32+0.31 MJ and RP = 1.552-0.057+0.048 RJ. This is the f
Title page WPSS WORKING PAPERS IN SCANDINAVIAN SYNTAX June 2016 Issue 96 Special issue on Icelandic Working Papers in Scandinavian Syntax is an electronic publication for current articles relating to the study of Scandinavian syntax. The articles appearing herein are previously unpublished reports of ongoing research activities and may subsequently appear, revised or unrevised, in other publicatio
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Untitled 1 O Estado de Direito Guia para políticos 2 Copyright © Instituto Raoul Wallenberg de Direitos Humanos e Direito Internacional Humanitário e Instituto de Haia para a Internacionalização do Direito 2012 ISBN: 978-91-86910-80-8 A distribuição desta publicação fica condicionada à sua não disponibilização, sob qualquer forma, exceto se previamente autorizada pelos editores. Mediante aprovação
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