Polymer matrix composites on LDEF experiments M0003-9 and M0003-10

Over 250 polymer matrix composites were exposed to the natural space environment on Long Duration Exposure Facility (LDEF) experiments M0003-9 and 10. The experiments included a wide variety of epoxy, thermoplastic, polyimide, and bismalimide matrix composites reinforced with graphite, glass, or organic fibers. A review of the significant observations and test results obtained to date is presented. Estimated recession depths from atomic oxygen exposure are reported and the resulting surface morphologies are discussed. The effects of the LDEF exposure on the flexural strength and modulus, short beam shear strength, and coefficient of thermal expansion of several classes of bare and coated composites are reviewed. Lap shear data are presented for composite-to-composite and composite-to-aluminum alloy samples that were prepared using different bonding techniques and subsequently flown on LDEF

Angoff anchor statements: setting a flawed gold standard?

http://www.mededpublish.org/manuscripts/120

Solvent Mediated Assembly of Nanoparticles Confined in Mesoporous Alumina

The controlled self-assembly of thiol stabilized gold nanocrystals in a mediating solvent and confined within mesoporous alumina was probed in situ with small angle x-ray scattering. The evolution of the self-assembly process was controlled reversibly via regulated changes in the amount of solvent condensed from an undersaturated vapor. Analysis indicated that the nanoparticles self-assembled into cylindrical monolayers within the porous template. Nanoparticle nearest-neighbor separation within the monolayer increased and the ordering decreased with the controlled addition of solvent. The process was reversible with the removal of solvent. Isotropic clusters of nanoparticles were also observed to form temporarily during desorption of the liquid solvent and disappeared upon complete removal of liquid. Measurements of the absorption and desorption of the solvent showed strong hysteresis upon thermal cycling. In addition, the capillary filling transition for the solvent in the nanoparticle-doped pores was shifted to larger chemical potential, relative to the liquid/vapor coexistence, by a factor of 4 as compared to the expected value for the same system without nanoparticles.Comment: 9 pages, 9 figures, appeared in Phys. Rev.

Analysis of macroautophagy related proteins in G2019S LRRK2 Parkinson's disease brains with Lewy body pathology

LRRK2, the gene encoding the multidomain kinase Leucine-Rich Repeat Kinase 2 (LRRK2), has been linked to familial and sporadic forms of Parkinson's disease (PD), as well as cancer, leprosy and Crohn's disease, establishing it as a target for discovery therapeutics. LRRK2 has been associated with a range of cellular processes, however its physiological and pathological functions remain unclear. The most prevalent LRRK2 mutations in PD have been shown to affect macroautophagy in various cellular models while a role in autophagy signalling has been recapitulated in vivo. Dysregulation of autophagy has been implicated in PD pathology, and this raises the possibility that differential autophagic activity is relevant to disease progression in PD patients carrying LRRK2 mutations. To examine the relevance of LRRK2 to the regulation of macroautophagy in a disease setting we examined the levels of autophagic markers in the basal ganglia of G2019S LRRK2 PD post-mortem tissue, in comparison to pathology-matched idiopathic PD (iPD), using immunoblotting (IB). Significantly lower levels of p62 and LAMP1 were observed in G2019S LRRK2 PD compared to iPD cases. Similarly, an increase in ULK1 was observed in iPD but was not reflected in G2019S LRRK2 PD cases. Furthermore, examination of p62 by immunohistochemistry (IH) recapitulated a distinct signature for G2019S PD. IH of LAMP1, LC3 and ULK1 broadly correlated with the IB results. Our data from a small but pathologically well-characterized cases highlights a divergence of G2019S PD carriers in terms of autophagic response in alpha-synuclein pathology affected brain regions compared to iPD

Measuring adolescents’ beliefs in conspiracy theories: Development and validation of the Adolescent Conspiracy Beliefs Questionnaire (ACBQ)

Four studies (total n = 961) developed and validated the Adolescent Conspiracy Beliefs Questionnaire (ACBQ). Initial items were developed in collaboration with teachers. An Exploratory Factor Analysis (Study 1, n = 208, aged 11-14) and a student focus group (N = 3, aged 11) enabled us to establish the factor structure of a 9-item scale. This was replicated via Confirmatory Factor Analysis in Study 2 (N = 178, aged 11-17), and the scale displayed good convergent (i.e., relationship with paranoia and mistrust) and discriminant validity (i.e., no relfationship with extraversion). Study 3a (N = 257) further tested convergent validity with a sample of 18-year olds (i.e., relationship with adult-validated measures of conspiracy beliefs), and demonstrated strong test re-test reliability. Study 3b (N = 318) replicated these findings with a mixed-age adult sample. The ACBQ will allow researchers to explore the psychological antecedents and consequences of conspiracy thinking in young populations

Differential LRRK2 signalling and gene expression in WT-LRRK2 and G2019S- LRRK2 mouse microglia treated with zymosan and MLi2

INTRODUCTION: Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene cause autosomal dominant Parkinson’s disease (PD) with the most common causative mutation being the LRRK2 p.G2019S within the kinase domain. LRRK2 protein is highly expressed in the human brain and also in the periphery, and high expression of dominant PD genes in immune cells suggest involvement of microglia and macrophages in inflammation related to PD. LRRK2 is known to respond to extracellular signalling including TLR4 resulting in alterations in gene expression, with the response to TLR2 signalling through zymosan being less known. METHODS: Here, we investigated the effects of zymosan, a TLR2 agonist and the potent and specific LRRK2 kinase inhibitor MLi-2 on gene expression in microglia from LRRK2-WT and LRRK2 p.G2019S knock-in mice by RNA-Sequencing analysis. RESULTS: We observed both overlapping and distinct zymosan and MLi-2 mediated gene expression profiles in microglia. At least two candidate Genome-Wide Association (GWAS) hits for PD, CathepsinB (Ctsb) and Glycoprotein-nmb (Gpnmb), were notably downregulated by zymosan treatment. Genes involved in inflammatory response and nervous system development were up and downregulated respectively with zymosan treatment while MLi-2 treatment particularly exhibited upregulated genes for ion transmembrane transport regulation. Furthermore, we observed the top twenty most significantly differentially expressed genes in LRRK2 p.G2019S microglia show enriched biological processes in iron transport and response to oxidative stress. DISCUSSION: Overall, these results suggest that microglial LRRK2 may contribute to PD pathogenesis through altered inflammatory pathways. Our findings should encourage future investigations of these putative avenues in the context of PD pathogenesis

An Abeis procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature flukes, 2 for mature flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis. Keywords: Abies procera, Abies grandis, Triterpenoid, Anthelmintic drug discovery, Neglected tropical diseases, Fasciola hepatica, Schistosoma manson

Aggregate distributional cost-effectiveness analysis of health technologies

Background Health inequalities can be partially addressed through the range of treatments funded by health systems. However, whilst health technology assessment agencies assess the overall balance of health benefits and costs, no quantitative assessment of health inequality impact is consistently undertaken. Methods The inequality impact of technologies recommended under the NICE single technology appraisal process from 2012-2014 is assessed using an aggregate distributional cost-effectiveness framework. Data on health benefits, costs and patient populations are extracted from the NICE website. Benefits for each technology are distributed to social groups using the observed socioeconomic distribution of hospital utilisation for the targeted disease. Inequality measures and estimates of cost-effectiveness are compared using the health inequality impact plane and combined using social welfare indices. Results Twenty-seven interventions are evaluated. 14 interventions are estimated to increase population health and reduce health inequality, eight to reduce population health and increase health inequality, and five to increase health and increase health inequality. Among the latter five, social welfare analysis, using inequality aversion parameters reflecting high concern for inequality, indicated that the health gain outweighs the negative health inequality impact. Conclusions The methods proposed offer a way of estimating the health inequality impacts of new health technologies. The methods do not allow for differences in technology-specific utilisation and health benefits, but require less resources and data than conducting full distributional cost-effectiveness analysis. They can provide useful quantitative information to help policy makers consider how far new technologies are likely to reduce or increase health inequalities