Model-independent dark energy test with sigma_8 using results from the Wilkinson Microwave Anisotropy Probe

By combining the recent WMAP measurements of the cosmic microwave background anisotropies and the results of the recent luminosity distance measurements to type-Ia supernovae, we find that the normalization of the matter power spectrum on cluster scales, sigma_8, can be used to discriminate between dynamical models of dark energy (quintessence models) and a conventional cosmological constant model (LCDM).Comment: 5 pages, 6 figures. Additional discussion and reference, matches PRD accepted versio

Enhanced liver fibrosis test : a further step toward depiction of fibrotic process in very early diagnosis of systemic sclerosis

Background/Purpose: Enhanced Liver Fibrosis (ELF) test is derived from an algorithm of 3 serum biomarkers of fibrosis (i.e. tissue inhibitors of matrix metalloproteinases, hyaluronic acid and aminoterminal propeptide of type III procollagen); it has been suggested as a sensitive/predictive tool for liver fibrosis. Aim of the study was to evaluate whether ELF may help in differentiating primary Raynaud\u2019s phenomenon (Rp) from very early Systemic Sclerosis (SSc) in a cross-sectional multi-center study. Methods: 110 consecutive adult subjects with \u201cisolated\u201d Rp (i.e. without any symptoms/signs suggesting a connective tissue disease) referring to 3 Italian Rheumatology Centers in approximately 6 months time were enrolled. Patients underwent as first screening nailfold capillaroscopy (NC) and were tested for anti-nuclear antibodies (ANA) by IFF and blotting and classified as primary Rp (pRp) (i.e. NC and ANA negative), very early SSc (i.e. ANA and NC positive), or Rp with NC or ANA positive. Patients with any other fibrosing disorder and treated with interferon were excluded. 15 limited cutaneous (lc)-SSc and 15 diffuse cutaneous (dc)-SSc with disease duration 5 years were also studied. ELF score was determined blindly by an independent commercial service (iQur, UK). Statistical analysis was performed by regression modelling this score as a function of the diagnosis and age. The discriminant performance was evaluate by ROC curve analysis adjusting for age. Results: 60 subjects had pRp (mean age 43.1 yrs), 35 had Rp with positive ANA only (mean age 43.6 yrs), 4 had Rp with NC scleroderma pattern only (mean age 38.2 yrs) and 10 had a diagnosis of very early SSc (mean age 59.7 yrs). There were significantly differences between ELF scores in subjects with pRp (mean 7.84) vs patients with very early SSc (mean 8.44), lc-SSc (mean 8.68) and dc-SSc (mean 9.00) (p 0.03, 0.001 and 0.0001 respectively). ELF score in pRp and Rp with positive ANA or NC scleroderma pattern only was not statistically different, although a progressive increase was observed (mean 7.84, 7.90 and 7.95 respectively). Considering patients with and without SSc, the area under the ROC curve was 0.7465 (CI 95%: 0.6578\u20130.8351). When adjusting for age the AUC for youngest patients was 0.77 and it significantly decreased for the older patients. A correlation was observed between ELF score and age. Conclusion: ELF score shows unbalanced fibrosis biomarkers in very early SSc; it may represent useful potential tool in identifying Rp associated with a scleroderma signature

Generation, characterization, and drug sensitivities of 12 patient-derived IDH1-mutant glioma cell cultures

Background: Mutations of the isocitrate dehydrogenase (IDH) gene occur in over 80% of low-grade gliomas and secondary glioblastomas. Despite considerable efforts, endogenous in vitro IDH-mutated glioma models remain scarce. Availability of these models is key for the development of new therapeutic interventions. Methods: Cell cultures were established from fresh tumor material and expanded in serum-free culture media. D-2-Hydroxyglutarate levels were determined by mass spectrometry. Genomic and transcriptomic profiling were carried out on the Illumina Novaseq platform, methylation profiling was performed with the Infinium MethylationEpic BeadChip array. Mitochondrial respiration was measured with the Seahorse XF24 Analyzer. Drug screens were performed with an NIH FDA-approved anti-cancer drug set and two IDH-mutant specific inhibitors. Results: A set of twelve patient-derived IDHmt cell cultures was established. We confirmed high concordance in driver mutations, copy numbers and methylation profiles between the tumors and derived cultures. Homozygous deletion of CDKN2A/B was observed in all cultures. IDH-mutant cultures had lower mitochondrial reserve capacity. IDH-mutant specific inhibitors did not affect cell viability or global gene expression. Screening of 107 FDA-approved anti-cancer drugs identified nine compounds with potent activity against IDHmt gliomas, including three compounds with favorable pharmacokinetic characteristics for CNS penetration: Teniposide, omacetaxine mepesuccinate, and marizomib. Conclusions: Our twelve IDH-mutant cell cultures show high similarity to the parental tissues and offer a unique tool to study the biology and drug sensitivities of high-grade IDHmt gliomas in vitro. Our drug screening studies reveal lack of sensitivity to IDHmt inhibitors, but sensitivity to a set of nine available anti-cancer agents

The management of HCV infected pregnant women and their children European paediatric HCV network

Background/Aims: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. Methods: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. Results/conclusions: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines. \ua9 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved