Growing pains? The transition to digital television in Europe

This article argues that national policies for digital television (DTV) are largely determined by markets, political contexts and supra-national influences, notably European Union (EU) audiovisual policy, which puts pressure on member states to speed up digital switchover.This creates a tension between the push of the EU to harmonize the switchover process and set target dates and the struggle of some of the countries to comply with this policy. In terms of the strategies that could be employed to accelerate digital uptake, the article points to setting a prompt date for analogue switch-off, subsidizing the relevant equipment to receive DTV, offering triple play services, ensuring active management to complete conversion effectively and, above all, adopting free-to-view DTV. The wide reach free-to-air model, in which public broadcasters have a leading role, ensures that the universality principle is maintained in the digital age

Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity

The Publisher's final version can be found by following the DOI link. open access articleWith the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity

Association between free testosterone levels and anal human papillomavirus Types 16/18 infections in a cohort of men who have sex with men

Background Human papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown. Methods Free testosterone (FT) was measured in serum from 340 Multicenter AIDS Cohort Study (MACS) participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing. Results Participants were, on average, 60 (+5.4) years of age, White (86%), and HIV-uninfected (56%); Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence= 17.1%, HPV18=9.1%). In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24) higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37) higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing) were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/ 18 infection in unadjusted and adjusted analyses. Conclusions Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years later, independent of sexual behavior and other potential confounders. The mechanisms underlying this association remain unclear and warrant further study

Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al

Madness decolonized?: Madness as transnational identity in Gail Hornstein’s Agnes’s Jacket

The US psychologist Gail Hornstein’s monograph Agnes’s Jacket: A Psychologist’s Search for the Meanings of Madness (2009) is an important intervention in the identity politics of the mad movement. Hornstein offers a resignified vision of mad identity that embroiders the central trope of an “anti-colonial” struggle to reclaim the experiential world “colonized” by psychiatry. A series of literal and figurative appeals make recourse to the inner world and (corresponding) cultural world of the mad, as well as to the ethno-symbolic cultural materials of dormant nationhood. This rhetoric is augmented by a model in which the mad comprise a diaspora without an origin, coalescing into a single transnational community. The mad are also depicted as persons displaced from their metaphorical homeland, the “inner” world “colonized” by the psychiatric regime. There are a number of difficulties with Hornstein’s rhetoric, however. Her “ethnicity-and-rights” response to the oppression of the mad is symptomatic of Western parochialism, while her proposed transmutation of putative psychopathology from limit upon identity to parameter of successful identity is open to contestation. Moreover, unless one accepts Hornstein’s porous vision of mad identity, her self-ascribed insider status in relation to the mad community may present a problematic “re-colonization” of mad experience

From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses

Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies

Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kB.

BACKGROUND: Endothelial MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the oxidant-dependent induction and progress of inflammatory bowel disease (IBD). Melatonin, a relatively safe, potent antioxidant, has shown efficacy in several chronic injury models may limit MAdCAM-1 expression and therefore have a therapeutic use in IBD. METHODS: We examined how different doses of melatonin reduced endothelial MAdCAM-1 induced by TNF-a in an in vitro model of lymphatic endothelium. Endothelial monolayers were pretreated with melatonin prior to, and during an exposure, to TNF-a (1 ng/ml, 24 h), and MAdCAM-1 expression measured by immunoblotting. RESULTS: MAdCAM-1 was induced by TNF-a. Melatonin at concentrations over 100 μm (10(-4) M) significantly attenuated MAdCAM-1 expression and was maximal at 1 mM. CONCLUSIONS: Our data indicate that melatonin may exert therapeutic activity in IBD through its ability to inhibit NF-kB dependent induction of MAdCAM-1

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.

The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3-6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First-visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65-5.41, P = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012-0.049, P = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared with using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at the group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalized objective disease activity monitoring for those living with amyotrophic lateral sclerosis