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

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

In situ He⁺ irradiation of the double solid solution (Ti_0.5,Zr_0.5)₂(Al_0.5,Sn_0.5)C MAX phase:Defect evolution in the 350–800 °C temperature range

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

Управление финансовой устойчивостью и рентабельностью предприятия

Целью статьи является изучение значения управления финансовой устойчивостью и рентабельностью предприятия в современных условиях хозяйствования

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

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

A comparison of psoriasis severity in pediatric patients treated with methotrexate vs biologic agents

This cohort study compares the use of methotrexate vs biologic agents in children with moderate to severe psoriasis. Question What is the association between use of methotrexate vs biologics and psoriasis severity and drug survival (rate and duration of adherence to a specific drug regimen) in pediatric patients with moderate to severe psoriasis? Findings In this cohort study including 234 pediatric patients with moderate to severe psoriasis, those receiving biologics were more likely than those treated with methotrexate to achieve a Physician Global Assessment status of clear/almost clear and 75% or more improvement of the Psoriasis Area and Severity Index rating at 6 months. In addition, biologics were associated with better drug survival rates at 1, 3, and 5 years, with comparable discontinuation rates owing to lack of response. Meaning In pediatric patients with psoriasis, treatment with biologics may be associated with a significantly greater reduction in psoriasis severity than methotrexate; nevertheless, with 35.6% of the patients achieving clear/almost clear and 40.0% reaching 75% or more improvement on the Psoriasis Area and Severity Index, methotrexate remains an effective treatment for pediatric psoriasis. Importance Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. Objective To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. Design, Setting, and Participants A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. Main Outcomes and Measures PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). Results Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). Conclusions and Relevance Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation

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

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

Existence of a Tribo-Modified Surface Layer on SBR Elastomers: Balance Between Formation and Wear of the Modified Layer

In most of the tribological contacts, the composition and tribological properties of the original interface will change during use. The tribo-films, with modified properties compared to the bulk, are dynamic structures that play a significant role in friction. The existence of a tribo-modified surface layer and its importance on the overall friction of elastomers has been shown both theoretically and experimentally before. The characteristics of the modified surface layer deserve specific attention since the tribological properties of elastomers in contact with a rough counter-surface are determined by these modified surfaces together with the properties of bulk of the material. Both the formation of the modified layer and the break down (wear) of it are of importance in determining the existence and thickness of the tribo-modified layer. In this study, the importance of the wear is emphasized by comparing two styrene butadiene rubber-based elastomers in contact with a granite sphere. A current status of perception of the removal and the stability of the modified surface layers on rubbers is introduced as well as experimental work related to this matter and discussion within literature. Pin-on-disk friction tests are performed on two SBR-based samples in contact with a granite sphere under controlled environmental conditions to form the modified surface layer. Although the hysteresis part of the friction force which has a minor contribution in the overall friction is not markedly different, the total measured friction coefficient differs significantly. Mechanical changes both inside and outside the wear track are determined by atomic force microscope nano-indentations at different timescales to examine the modified surface layer on the test samples. The specific wear rates of the two tribo-systems are compared, and the existence of the modified surface layer, the different measured friction coefficient and the running-in distances toward steady-state friction are explained considering different wear rates. A conceptual model is presented, correlating the energy input into the tribo-system and the existence of a modified surface layer

Organic and inorganic compounds in limestone weathering crusts from cathedrals in Southern and Western Europe

Limestone and weathering crusts have been studied at the major cathedrals of Sevilla, in southwestern Spain, and Mechelen, in northern Belgium. These cities have very different climatic and environmental conditions. The deterioration characteristics of the limestone in both localities have been compared. Detailed petrographical characterization was carried out for the different building stones, including restoration materials. The bulk and trace inorganic composition of the stones and crusts was assessed, and the leachable ions were analyzed, while elemental concentration profiles with depth were studied with electron microprobe analysis. The organic compounds in the black weathering crusts have also been studied and compared. In the different types of limestone, the deterioration is largely influenced by the petrographie characteristics of the stone. Gypsum crusts from Mechelen and Sevilla show variable textures, even on the same stone types. Sulfatation of calcite provides Ca for the gypsum crusts. Except fora part of the Sr and Fe fractions in the crust, all other elements may be of external origin. Concentrations of the various elements are more or less comparable in crusts from Mechelen and Sevilla. External inorganic particles consist of fly ash, quartz, clay, and glauconite. Most of the organic material appeared to be of anthropogenic origin, due to combustion processes, while a minor fraction originated from cuticular waxes of higher plants.This work was supported by the Commission of the European Community, Project STEP-CT90-0107.Peer Reviewe

RFT1-CDG: Deafness as a novel feature of congenital disorders of glycosylation

Congenital disorders of glycosylation (CDG) are genetic diseases due to defects in the synthesis of glycans and in the attachment of glycans to lipids and proteins. Actually, some 42 CDG are known including defects in protein N-glycosylation, in protein O-glycosylation, in lipid glycosylation, and in multiple and other glycosylation pathways. Most CDG are multisystem diseases and a large number of signs and symptoms have already been reported in CDG. An exception to this is deafness. This symptom has not been observed as a consistent feature in CDG. In 2008, a novel defect was identified in protein N-glycosylation, namely in RFT1. This is a defect in the assembly of N-glycans. RFT1 is involved in the transfer of Man(5)GlcNAc(2)-PP-Dol from the cytoplasmic to the luminal side of the endoplasmic reticulum. According to the novel nomenclature (non-italicized gene symbol followed by -CDG) this defect is named RFT1-CDG. Recently, three other patients with RFT1-CDG have been reported and here we report two novel patients. Remarkably, all six patients with RFT1-CDG show sensorineural deafness as part of a severe neurological syndrome. We conclude that RFT1-CDG is the first 'deafness-CDG'. CDG should be included in the work-up of congenital, particularly syndromic, hearing loss