Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma

The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura

The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells

Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres

Online Mathematics Homework Increases Student Achievement

In a randomized field trial with 2,850 seventh-grade mathematics students, we evaluated whether an educational technology intervention increased mathematics learning. Assigning homework is common yet sometimes controversial. Building on prior research on formative assessment and adaptive teaching, we predicted that combining an online homework tool with teacher training could increase learning. The online tool ASSISTments (a) provides timely feedback and hints to students as they do homework and (b) gives teachers timely, organized information about students’ work. To test this prediction, we analyzed data from 43 schools that participated in a random assignment experiment in Maine, a state that provides every seventh-grade student with a laptop to take home. Results showed that the intervention significantly increased student scores on an end-of-the-year standardized mathematics assessment as compared with a control group that continued with existing homework practices. Students with low prior mathematics achievement benefited most. The intervention has potential for wider adoption

Keep it simple: three indicators to deal with overfishing

Three simple fisheries indicators are presented: (i) percentage of mature fish in catch, with 100% as target; (ii) percent of specimens with optimum length in catch, with 100% as target; and (iii) percentage of ‘mega-spawners‘ in catch, with 0% as target, and 30–40% as representative of reasonable stock structure if no upper size limit exists. Application of these indicators to stocks of Gadus morhua, Sardinella aurita and Epinephelus aeneus demonstrate their usefulness. It is argued that such simple indicators have the potential to allow more stakeholders such as fishers, fish dealers, supermarket managers, consumers and politicians to participate in fisheries management and eventually hold and reverse the global pattern of convenience overfishing, which is defined here as deliberate overfishing sanctioned by official bodies who find it more convenient to risk eventual collapse of fish stocks than to risk social and political conflicts

Online Resource to Promote Vocational Interests Among Job Seekers With Multiple Sclerosis: A Randomized Controlled Trial in Australia

© 2017 American Congress of Rehabilitation Medicine Objective: To provide a preliminary evaluation of the effectiveness of an online resource for job seekers with multiple sclerosis (MS). Design: Randomized controlled design. Setting: Community-dwelling cohort. Participants: Adults (N = 95) with relapsing-remitting or progressive MS were randomly assigned to one of two groups. Forty-five accessed an email delivered, 7 module resource, Work and MS, over a 4 week period. Waitlist control participants (n=50) were offered the opportunity to access Work and MS 4 weeks postenrollment. Main Outcome Measures: Primary outcomes focused on vocational interests (My Vocational Situation Scale) and self-efficacy in job-seeking activities (Job-Procurement Self Efficacy Scale). Secondary outcomes focused on perceived workplace difficulties (Multiple Sclerosis Work Difficulties Questionnaire [MSWDQ]), optimism (Life Orientation Test – Revised), and mood (Patient Health Questionnaire-9). Results: Intention-to-treat analyses revealed pre-post gains: participants who accessed Work and MS reported improved confidence in their career goals (My Vocational Situation Scale g=.55; 95% confidence interval [CI],.14–.96; P=.008) and positively reappraised potential workplace difficulties (MSWDQ g range,.42–.47; P range,.023–.042). The effect on job self-efficacy was not significant, but changed in the expected direction (g=.17; 95% CI, –.23 to.57; P=.409). Completer data revealed larger, significant effect estimates (g range,.52–.64; P range,.009–.035). Conclusions: Findings provide preliminary support for the utility of a job information resource, Work and MS, to augment existing employment services. The results also suggest the need to test employment-ready interventions in a larger study population. This might include the addition of online peer support to increase intervention compliance

Radical coupling of aryl halides to arenes facilitated by Ni(COD)(DQ) and other nickel sources

The air-stable complex Ni(COD)(DQ) (COD = 1,5-cyclooctadiene, DQ = duroquinone) promotes the coupling of aryl halides to arenes in the presence of KOtBu. This complex has recently been shown to perform coupling reactions based on organonickel intermediates, but in this case the coupling reactions proceed via aryl radicals as shown by our newly developed assay for aryl radicals. Coupling with this nickel source is more efficient than with Ni(COD)2, Ni(PPh3)4 and Ni(acac)2, all of which we also show to operate through aryl radical pathways

Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation

Interleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage function through engagement of a novel receptor (IL-23R) on these cells. Recent analysis of the contribution of IL-12 and IL-23 to central nervous system autoimmune inflammation demonstrated that IL-23 rather than IL-12 was the essential cytokine. Using gene-targeted mice lacking only IL-12 (p35−/−) or IL-23 (p19−/−), we show that the specific absence of IL-23 is protective, whereas loss of IL-12 exacerbates collagen-induced arthritis. IL-23 gene-targeted mice did not develop clinical signs of disease and were completely resistant to the development of joint and bone pathology. Resistance correlated with an absence of IL-17–producing CD4+ T cells despite normal induction of collagen-specific, interferon-γ–producing T helper 1 cells. In contrast, IL-12–deficient p35−/− mice developed more IL-17–producing CD4+ T cells, as well as elevated mRNA expression of proinflammatory tumor necrosis factor, IL-1β, IL-6, and IL-17 in affected tissues of diseased mice. The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation

Work and SCI: a pilot randomized controlled study of an online resource for job-seekers with spinal cord dysfunction.

STUDY DESIGN:A prospective, parallel randomized controlled trial (RCT). OBJECTIVES:To test the preliminary effects of an online resource targeted to job-seekers with spinal cord injury or disorder (SCI/D), and to determine the feasibility of proceeding to a full-scale RCT. SETTING:A community cohort in Australia. METHODS:Forty-eight adults (M = 42 years, SD = 10.95, 27 males) were randomized to receive 4-weeks access to the Work and SCI resource (n = 25) or to a wait-list control group (n = 23). The Work and SCI intervention involved six stand-alone learning modules which provided job-searching and career-planning information through text, videos, and interactive activities. Self-report measures were administered at baseline and after 4 weeks: Job Procurement Self-Efficacy Scale (JSES), Life Orientation Test-Revised (LOT-R), and Patient Health Questionnaire-9 (PHQ-9). RESULTS:Online usage data identified high uptake of the Work and SCI resource, although study attrition was problematic. Intention-to-treat analyses failed to reach statistical significance, whereas complete data revealed a significant interaction effect for optimism (LOT-R). CONCLUSION:Further research to develop and enhance Work and SCI is indicated. Remediable strategies to optimize recruitment and statistical power in a future definitive RCT are discussed. SPONSORSHIP:This project was funded by the auDA Foundation (project 16019)

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base