Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats

The increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague-Dawley (SD) rats.We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 μg/mm(3); mean diameter: 13-16 nm; total lung doses: 8 [Low] and 26-28 [High] μg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function.In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1β, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains.Presence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma

Introduction Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC. Methods A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results The median number of cycles administered was 6 (range 1–6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression-free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC). Conclusions Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma

Low-frequency gravitational-wave science with eLISA/NGO

We review the expected science performance of the New Gravitational-Wave Observatory (NGO, a.k.a. eLISA), a mission under study by the European Space Agency for launch in the early 2020s. eLISA will survey the low-frequency gravitational-wave sky (from 0.1 mHz to 1 Hz), detecting and characterizing a broad variety of systems and events throughout the Universe, including the coalescences of massive black holes brought together by galaxy mergers; the inspirals of stellar-mass black holes and compact stars into central galactic black holes; several millions of ultracompact binaries, both detached and mass transferring, in the Galaxy; and possibly unforeseen sources such as the relic gravitational-wave radiation from the early Universe. eLISA's high signal-to-noise measurements will provide new insight into the structure and history of the Universe, and they will test general relativity in its strong-field dynamical regime.Comment: 20 pages, 8 figures, proceedings of the 9th Amaldi Conference on Gravitational Waves. Final journal version. For a longer exposition of the eLISA science case, see http://arxiv.org/abs/1201.362

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

BACKGROUND: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. METHODS: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. RESULTS: Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. CONCLUSIONS: A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas (http://clinicaltrials.gov/ct2/show/NCT02220855)

Measuring the health impact of human rights violations related to Australian asylum policies and practices: A mixed methods study

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Johnston et al.BACKGROUND: Human rights violations have adverse consequences for health. However, to date, there remains little empirical evidence documenting this association, beyond the obvious physical and psychological effects of torture. The primary aim of this study was to investigate whether Australian asylum policies and practices, which arguably violate human rights, are associated with adverse health outcomes. METHODS: We designed a mixed methods study to address the study aim. A cross-sectional survey was conducted with 71 Iraqi Temporary Protection Visa (TPV) refugees and 60 Iraqi Permanent Humanitarian Visa (PHV) refugees, residing in Melbourne, Australia. Prior to a recent policy amendment, TPV refugees were only given temporary residency status and had restricted access to a range of government funded benefits and services that permanent refugees are automatically entitled to. The quantitative results were triangulated with semi-structured interviews with TPV refugees and service providers. The main outcome measures were self-reported physical and psychological health. Standardised self-report instruments, validated in an Arabic population, were used to measure health and wellbeing outcomes. RESULTS: Forty-six percent of TPV refugees compared with 25% of PHV refugees reported symptoms consistent with a diagnosis of clinical depression (p = 0.003). After controlling for the effects of age, gender and marital status, TPV status made a statistically significant contribution to psychological distress (B = 0.5, 95% CI 0.3 to 0.71, p </= 0.001) amongst Iraqi refugees. Qualitative data revealed that TPV refugees generally felt socially isolated and lacking in control over their life circumstances, because of their experiences in detention and on a temporary visa. This sense of powerlessness and, for some, an implicit awareness they were being denied basic human rights, culminated in a strong sense of injustice. CONCLUSION: Government asylum policies and practices violating human rights norms are associated with demonstrable psychological health impacts. This link between policy, rights violations and health outcomes offers a framework for addressing the impact of socio-political structures on health.This research was supported by an Australian National and Medical Research Council PhD Scholarship (N. 251782) and a Victorian Health Promotion Foundation research grant (No. 2002-0280)

Perceptions of animal physiotherapy amongst Irish veterinary surgeons

The aim of this study was to investigate veterinary surgeons' perceptions, knowledge and use of animal physiotherapy in the Republic of Ireland. A questionnaire was developed and sent to 200 veterinary surgeons, of which 97 were returned. Results indicated that 77 (79%) of respondents were aware of animal physiotherapists. Common sources of information included veterinary colleagues, owners and professional journals, with physiotherapists themselves and undergraduate training being less commonly cited. Awareness of animal physiotherapy was greatest amongst those working in equine practice (χ2 = 5.7, df 1, p = 0.017); they were more knowledgeable about its techniques (t = 2.806, df 75, p = 0.006) and more likely to refer (χ2 = 48.36, df 1, p = 0.0001). Seventy-four respondents (96%) thought that more research was necessary to increase the evidence base for animal physiotherapy. If this branch of physiotherapy is to develop, there needs to be increased interaction and co-operation between veterinary surgeons and chartered animal physiotherapists

A Measurement of the Spatial Distribution of Diffuse TeV Gamma Ray Emission from the Galactic Plane with Milagro

Diffuse $\gamma$-ray emission produced by the interaction of cosmic-ray particles with matter and radiation in the Galaxy can be used to probe the distribution of cosmic rays and their sources in different regions of the Galaxy. With its large field of view and long observation time, the Milagro Gamma Ray Observatory is an ideal instrument for surveying large regions of the Northern Hemisphere sky and for detecting diffuse $\gamma$-ray emission at very high energies. Here, the spatial distribution and the flux of the diffuse $\gamma$-ray emission in the TeV energy range with a median energy of 15 TeV for Galactic longitudes between 30$^\circ$ and 110$^\circ$ and between 136$^\circ$ and 216$^\circ$ and for Galactic latitudes between -10$^\circ$ and 10$^\circ$ are determined. The measured fluxes are consistent with predictions of the GALPROP model everywhere except for the Cygnus region ($l\in[65^\circ,85^\circ]$). For the Cygnus region, the flux is twice the predicted value. This excess can be explained by the presence of active cosmic ray sources accelerating hadrons which interact with the local dense interstellar medium and produce gamma rays through pion decay.Comment: 15 pages, 3 figures, accepted by Ap

Disease Progression and Serological Assay Performance in Heritage Breed Pigs following Brucella suis Experimental Challenge as a Model for Naturally Infected Feral Swine

Invasive feral swine (Sus scrofa) are one of the most important wildlife species for disease surveillance in the United States, serving as a reservoir for various diseases of concern for the health of humans and domestic animals. Brucella suis, the causative agent of swine brucellosis, is one such pathogen carried and transmitted by feral swine. Serology assays are the preferred field diagnostic for B. suis infection, as whole blood can be readily collected and antibodies are highly stable. However, serological assays frequently have lower sensitivity and specificity, and few studies have validated serological assays for B. suis in feral swine. We conducted an experimental infection of Ossabaw Island Hogs (a breed re-domesticated from feral animals) as a disease-free proxy for feral swine to (1) improve understanding of bacterial dissemination and antibody response following B. suis infection and (2) evaluate potential changes in the performance of serological diagnostic assays over the course of infection. Animals were inoculated with B. suis and serially euthanized across a 16-week period, with samples collected at the time of euthanasia. The 8% card agglutination test performed best, whereas the fluorescence polarization assay demonstrated no capacity to differentiate true positive from true negative animals. Froma disease surveillance perspective, using the 8%card agglutination test in parallel with either the buffered acidified plate antigen test or the Brucella abortus/suis complement fixation test provided the best performance with the highest probability of a positive assay result. Application of these combinations of diagnostic assays for B. suis surveillance among feral swine would improve understanding of spillover risks at the national level