326 research outputs found

    Self-consistent field predictions for quenched spherical biocompatible triblock copolymer micelles

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    We have used the Scheutjens-Fleer self-consistent field (SF-SCF) method to predict the self-assembly of triblock copolymers with a solvophilic middle block and sufficiently long solvophobic outer blocks. We model copolymers consisting of polyethylene oxide (PEO) as solvophilic block and poly(lactic-co-glycolic) acid (PLGA) or poly({\ko}-caprolactone) (PCL) as solvophobic block. These copolymers form structurally quenched spherical micelles provided the solvophilic block is long enough. Predictions are calibrated on experimental data for micelles composed of PCL-PEO-PCL and PLGA-PEO-PLGA triblock copolymers prepared via the nanoprecipitation method. We establish effective interaction parameters that enable us to predict various micelle properties such as the hydrodynamic size, the aggregation number and the loading capacity of the micelles for hydrophobic species that are consistent with experimental finding.Comment: accepted for publication in Soft Matte

    Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women

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    Background: Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case–control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies. Methods: We conducted a cohort study among 108 578 women in the Nurses' Health Study (1976–2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood. Results: Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2–10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10−4 Robertson–Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC. Conclusions: Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers

    In situ He<sup>+</sup> irradiation of the double solid solution (Ti<sub>0.5</sub>,Zr<sub>0.5</sub>)<sub>2</sub>(Al<sub>0.5</sub>,Sn<sub>0.5</sub>)C MAX phase:Defect evolution in the 350–800 °C temperature range

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    Thin foils of the double solid solution (Zr0.5,Ti0.5)2(Al0.5,Sn0.5)C MAX phase were in situ irradiated in a transmission electron microscope (TEM) up to a fluence of 1.3 × 1017 ions⋅cm-2 (∼7.5 dpa), using 6 keV He+ ions. Irradiations were performed in the 350–800 °C temperature range. In situ and post-irradiation examination (PIE) by TEM was used to study the evolution of irradiation-induced defects as function of dose and temperature. Spherical He bubbles and string-like arrangements thereof, He platelets, and dislocation loops were observed. Dislocation loop segments were found to lie in non-basal-planes. At irradiation temperatures ≥ 450 °C, grain boundary tearing was observed locally due to He bubble segregation. However, the tears did not result in transgranular crack propagation. The intensity of specific spots in the selected area electron diffraction patterns weakened upon irradiation at 450 and 500 °C, indicating an increased crystal symmetry. Above 700 °C this was not observed, indicating damage recovery at the high end of the investigated temperature range. High-resolution scanning TEM imaging performed during the PIE of foils previously irradiated at 700 °C showed that the chemical ordering and nanolamination of the MAX phase were preserved after 7.5 dpa He+ irradiation. The size distributions of the He platelets and spherical bubbles were evaluated as function of temperature and dose.</p

    Temporal resolution deficits in the visual fields of MS patients

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    AbstractWe assessed the relationship between temporal resolution and MS-induced neuropathy. A diagnostic strategy comprising assessments of temporal resolution at 16 points in the extra-foveal visual field up to 12° from the fovea was first compared with foveal temporal resolution and with a standard VEP procedure in the same MS patients. At the group level, foveal temporal resolution was less sensitive to demyelination than the 16-point diagnostic strategy, the detection rate of which was comparable to that of the VEP procedure. Cross-sensitivity of the VEP and the 16-point diagnostic procedure was low. Subsequently, the average severity of MS-induced temporal resolution deficits was studied at three retinal loci of the same size but different eccentricities. Foveal deficits were not significantly greater than more peripheral deficits within the central 12°

    A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

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    OBJECTIVES: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. METHODS: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. RESULTS: Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. DISCUSSION: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients

    Roles of pathway-based models and their contribution to the redesign of health-care systems

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    Care pathways provide a practical analytical tool that encompasses both organizational efficiency and individual patients'care. In the UK, constructing the care pathway has been a recommended starting point for the re-design of health-caresystems. This paper examines the re-design cycle for health-care systems and looks at the role of pathway-basedmodels in the design and operation phases of the cycle. In addition, the models provide further benefits for communicatingrecommended practice and audit of care and outcomes. The models span the classic care pathway with extensions tosimulation modelling. An example of the use of care pathways in the re-design of an emergency department is used forillustration. This study shows the role of pathway models as: a tool for re-design, a catalyst for enhancing communicationand as a repository for audit information. The final role of a tool for modelling contingencies was not implemented. Fromthe example it can be concluded that sophisticated models can be useful, in some applications; however, the simplerapproaches may often be the best, offering rapid, transparent recommendations based on a multidisciplinary approach

    Bone Tissue Response to Porous and Functionalized Titanium and Silica Based Coatings

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    Background: Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. Methodology: Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO2); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 mm, BAF-500), in the implant vicinity (100 mm, BAF-100) and further away (100–500 mm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. Principal Findings: After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p.0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-mm compared to the 400-mm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. Conclusions: BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didn’t stimulate bone regeneration but allowed bone growth into the pores. Although AMS didn’t stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation.status: publishe
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