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An iterative step-growth synthesis up to 26 viologen subunits is established for unimolecular polyviologens on a gram scale. Facile degradation of the polyviologens under mildly basic conditions was demonstrated in solution and in hydrogel networks.

PurposeProject portfolio risk (PPR) management plays an important role in promoting the smooth implementation of a project portfolio (PP). Accurate PPR prediction helps managers cope with risks timely in complicated PP environments. However, studies on accurate PPR impact degree prediction, which consists of both risk occurrence probabilities and risk impact consequences considering project interactions, are limited. This study aims to model PPR prediction and expand PPR prediction tools.Design/methodology/approachIn this study, the authors build a PPR prediction model based on a genetic algorithm and back-propagation neural network (GA-BPNN) integrated with entropy-trapezoidal fuzzy numbers. Then, the authors verify the proposed model with real data and obtain PPR impact degrees.FindingsThe test results indicate that the proposed method achieves an average absolute error of 0.002 and an average prediction accuracy rate of 97.8%. The former is reduced by 0.038, while the latter is improved by 32.1% when compared with the results of the original BPNN model. Finally, the authors conduct an index sensitivity analysis for identifying critical risks to effectively control them.Originality/valueThis study develops a hybrid PPR prediction model that integrates a GA-BPNN with entropy-trapezoidal fuzzy numbers. The authors use this model to predict PPR impact degrees, which consist of both risk occurrence probabilities and risk impact consequences considering project interactions. The results provide insights into PPR management.

International audience; This paper studies a multi-period closed-loop inventory routing problem for perishable food that are carried by returnable transport items (RTIs) of different types. We formulate the problem as an integer linear programming (ILP) model considering RTIs with different food quality preserve ability, and the simultaneous delivery of food and pick-up of RTIs. The objective is to maximize the total profit of the holistic supply chain that equals to the selling revenue minus the summation of production, routing, inventory and RTI purchase costs. The proposed model is demonstrated to be correct and effective by conducting computational experiments on randomly generated instances.

The design and synthesis of a novel multifunctional core initiator based on γ-cyclodextrin (γ-CD) functionalized with eight norbornenes is reported, and a core-first approach to make eight-arm star polymers using ring-opening metathesis polymerization is carried out by grafting-from the initiator using norbornene-functionalized hexaethylene glycol. The living nature of the polymerization was verified through chain extension of the ω-functional arms with norbornene-functionalized poly(ethylene glycol) (PEG, Mn ≈ 2 kDa) to generate water-soluble diblock brush-arm star copolymers (DBASCs) with high molar masses (Mn,NMR = 187–268 kDa) and low dispersities (Đ = 1.12–1.19). The size of the corresponding star polymers was confirmed by transmission electron microscopy and dynamic light scattering (Dh ≈ 10.0–11.0 nm). The thermal properties (e.g., Tg) of the DBASCs were determined by thermogravimetric analysis and differential scanning calorimetry, the latter of which showed well-ordered materials in the solid state (prominent Tc and Tm peaks). The long-range order and crystallinity of solid-state DBASCs was further supported by well-defined powder X-ray diffraction patterns. Lastly, since γ-CD possesses an order of magnitude greater solubility in water and enhanced drug-binding capabilities compared to that for β-CD, a representative DBASC was evaluated against healthy human umbilical vein endothelial cells (and exhibited low toxicity), and was also investigated as a delivery vehicle for the anticancer drug doxorubicin as its hydrochloride salt (DOX·HCl), resulting in greater potency against MCF-7 breast cancer cells relative to that of the free DOX·HCl treatment. The star polymers reported herein represent a new modular polymeric platform with potential applications in nanostructure self-assembly and drug delivery.

International audience; Closed-loop supply chains (CLSC) for food products mostly focus on the recovery of the residual value of food itself. Food packaging that plays an important role in food supply chain has rarely been studied. This paper aims to investigate an integrated multi-period closed-loop food supply chain planning problem with returnable transport items (RTIs) in which the total profit and the environmental impact are simultaneously considered. For the problem, an improved bi-objective mixed-integer linear program is formulated with obtained valid inequalities. Especially, the model with valid inequalities can reduce nearly 50% of the average computation time compared with the initial one. To solve the problem, a kernel-search heuristic based ε-constraint method is developed to obtain an approximate Pareto front. Finally, a fuzzy logic-based technique is adapted to help decision makers select a preferred solution according to his/her preference. A real case study from a slaughterhouse illustrates that the proposed method can improve the company’s current strategy for a 7-day planning. Computational results of randomly generated instances demonstrate that the proposed method outperforms the exact ε-constraint method in terms of computational time while providing good approximation.

Organic–inorganic hybrid perovskite materials exhibit excellent features in the photovoltaic applications. However, there are still questions unanswered regarding fundamental mechanisms of high-performance perovskite devices. Hall Effect and time-resolved photoluminescence measurements are conducted in our research to reveal the nature of carrier transport in CH3NH3I3 single crystals. We found that the high mobility of the crystals falls with increasing temperature, while the slow recombination rate constant of the crystals increases with increasing temperature. The former supports that coherent transport takes place in the CH3NH3PbI3 single crystals, whereas the latter evidences that photo-induced minority carriers exhibit their heavy effective mass in the transport. The two apparently distinct features are complementary in the description of the nature of polaronic motions in the CH3NH3PbI3 materials. These dynamical considerations depict a large polaron moving slowly while scattering with phonons in the CH3NH3PbI3 single crystals.

Despite the progress in the area of food safety, foodborne diseases still represent a massive challenge to the public health systems worldwide, mainly due to the substantial inefficiencies across the farm-to-fork continuum. Here, we report the development of a nano-carrier platform, for the targeted and precise delivery of antimicrobials for the inactivation of microorganisms on surfaces using Engineered Water Nanostructures (EWNS). An aqueous suspension of an active ingredient (AI) was used to synthesize iEWNS, with the ‘i’ denoting the AI used in their synthesis, using a combined electrospray and ionization process. The iEWNS possess unique, active-ingredient-dependent physicochemical properties: i) they are engineered to have a tunable size in the nanoscale; ii) they have excessive electric surface charge, and iii) they contain both the reactive oxygen species (ROS) formed due to the ionization of deionized (DI) water, and the AI used in their synthesis. Their charge can be used in combination with an electric field to target them onto a surface of interest. In this approach, a number of nature-inspired antimicrobials, such as H2O2, lysozyme, citric acid, and their combination, were used to synthesize a variety of iEWNS-based nano-sanitizers. It was demonstrated through foodborne-pathogen-inactivation experiments that due to the targeted and precise delivery, and synergistic effects of AI and ROS incorporated in the iEWNS structure, a pico-to nanogram-level dose of the AI delivered to the surface using this nano-carrier platform is capable of achieving 5-log reductions in minutes of exposure time. This aerosol-based, yet ‘dry’ intervention approach using iEWNS nano-carrier platform offers advantages over current ‘wet’ techniques that are prevalent commercially, which require grams of the AI to achieve similar inactivation, leading to increased chemical risks and chemical waste byproducts. Such a targeted nano-carrier approach has the potential to revolutionize the delivery of antimicrobials for sterilization in the food industry.

OBJECTIVEThis article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).METHODSTwenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9–45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1–34.6 cm3). The median interval between stages was 10 months (range 6–12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18–98 months).RESULTSPeriodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.CONCLUSIONSThis retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.

The self-assembly of Co(ii) salts, pyridazine derivatives and azides afforded two azido-bridged [2×2] grid-type complexes {[(L)4CoII4(N3)4][BPh4]4}·sol (1, L = 3,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (pzdz) and sol = 4CH3CN·3CHCl3·2CH3OH and 2, L = 3,6-di(pyridin-2-yl)pyridazine (pydz) and sol = 4CH3CN). Upon comparison with other related grid-like complexes, the incorporation of end-on azido-bridges resulted in overall intramolecular ferromagnetic couplings, and thus endowed complexes 1 and 2 single molecule magnet behaviour with field-induced slow magnetic relaxation.

A forced cycle C of a graph G is a cycle in G such that G − V ( C ) has a unique perfect matching. A graph G is a cycle-forced graph if every cycle in G is a forced cycle. In this paper, we give a characterization of cycle-forced hamiltonian bipartite graphs.

International audience; Closed-loop supply chain (CLSC) is of utmost importance to sustainable development and has received increasing attention in recent decades. However, food CLSC with returnable transport items (RTIs) has been rarely studied although its growing applications in practice. This paper aims to investigate a multi-period CLSC planning problem that coordinates the flows of perishable food products and RTIs considering food quality. The objective is to maximise the total profit of the holistic supply chain over a finite planning horizon. To this end, a novel mixed integer linear programming model is first formulated. As the problem is proven NP-hard, an improved kernel search-based heuristic is then developed. A real case study deriving from a food manufacturer in China shows the applicability of the proposed model and method. The results indicate that the manufacturer’s profit can be improved by more than 10% with our method. Numerical experiments on randomly generated instances demonstrate that the proposed heuristic can yield high-quality solutions with much less computation time compared with the commercial solver CPLEX and an existing heuristic.

Electronic cigarettes (e-cigs) have fast increased in popularity but the physico-chemical properties and toxicity of the generated emission remain unclear. Reactive oxygen species (ROS) are likely present in e-cig emission and can play an important role in e-cig toxicity. However, e-cig ROS generation is poorly documented. Here, we generated e-cig exposures using a recently developed versatile exposure platform and performed systematic ROS characterization on e-cig emissions using complementary acellular and cellular techniques: 1) a novel acellular Trolox-based mass spectrometry method for total ROS and hydrogen peroxide (H2O2) detection, 2) electron spin resonance (ESR) for hydroxyl radical detection in an acellular and cellular systems and 3) in vitro ROS detection in small airway epithelial cells (SAEC) using the dihydroethidium (DHE) assay. Findings confirm ROS generation in cellular and acellular systems and is highly dependent on the e-cig brand, flavor, puffing pattern and voltage. Trolox method detected a total of 1.2–8.9 nmol H2O2 eq./puff; H2O2 accounted for 12–68 % of total ROS. SAEC cells exposed to e-cig emissions generated up to eight times more ROS compared to control. The dependency of e-cig emission profile on e-cig features and operational parameters should be taken into consideration in toxicological studies.

Halogen-based fire retardants are often used to reduce flammability and improve the fire resistance properties of polymers and fiber-reinforced polymer composites (FRPs). Brominated vinyl ester resins (Br-VERs) are a class of halogenated polymer matrices that are economically viable, high performance materials that are widely utilized in composites for specialty applications, such as the fabrication of hulls in naval vessels. In this work, Br-VE polymer is synthesized from tetrabromobisphenol A (TBBPA) and glycidyl methacrylate (GMA) precursors, and which can be derived from the wastes of the biodiesel and wood pulp industries, respectively. The Br-VE reaction products are analyzed by 1H NMR and the presence of unreacted (nonfunctional), monofunctional and difunctional TBBPA are confirmed. A baseline formulation of difunctional Br-VE and styrene (40 wt %) is mixed with a commercial brominated vinyl ester resin (Derakane 510-40A) in ratios of 20, 50 and 80 pph. Two reduced styrene content formulations of Br-VER (30 wt % styrene and 20 wt % styrene) were also prepared. The thermomechanical properties of all seven neat resin formulations were investigated using differential scanning calorimetry (DSC), rheology and dynamic mechanical analysis (DMA). The autocatalytic cure kinetics parameters and chemorheological behavior enable development of a cure cycle for the thermosetting resin. The DMA results demonstrate that all resin formulations comprising Br-VER exhibit improved mechanical performance as compared to the commercial vinyl ester resin.

A bi-objective model for multi-floor facility layout problem with fixed inner configuration.The aim is to minimize both the total material handling cost and total occupied room area.An exact -constraint method is employed to solve the model.Real-life and randomly generated instances are used to validate the approach. The conventional facility layout problem (FLP) is concerned with arranging a number of interacting facilities, such as machines or departments, within a single-floor or multi-floor space to satisfy one or more objectives. In this paper, we devote ourselves to treating a novel bi-objective multi-floor FLP with fixed inner configuration and room adjacency constraints. In our problem, a given number of departments with required areas need to be arranged in a multi-floor building with fixed room configuration and the rooms of the same department should be adjacent to each other. In order to formulate the problem, a bi-objective mixed integer non-linear programming model is first proposed. The objective is to simultaneously minimize the total material handling cost among all the departments and the total occupied room area. The model is then linearized and further improved by determining the lower bound on the number of rooms occupied by each department. With the purpose of obtaining all Pareto optimal solutions, we employ an exact -constraint method to solve the model. Computational experiments on a real-life instance and randomly generated instances are conducted to validate the effectiveness of the proposed approach.

The high speed railway (HSR) network in China has developed rapidly over the past ten years, offering a new means of travel and also regenerating and redistributing economic activities by encouraging population mobility. Using the Yangtze River Delta urban agglomeration as a case study, this paper investigates the redistribution of economic activities resulting from HSRs by developing a locally weighted regression model, geographically network weighted regression (GNWR). This GNWR is formulated in light of the current account identity in economics, and incorporates the changes in network-based travel time from HSRs and the degrees of cities, thereby offering a more appropriate method of capturing the movement of economic activities. Importantly, the coefficients in GNWR can reflect the net inflow or outflow of different cities in terms of their residents' investment and/or consumption. The results of the analysis show that HSRs have significantly changed the spatial redistribution of economic activities due to more frequent and rapid mobility. For investment activities, HSR drew the inflow to the second tier cities alongside HSR and strengthened the status of core cities; for consumption activities, HSR motivated the inflow to non-HSR cities located in the peripheral areas.

Background Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. Results Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. Conclusion Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.

Inhalation exposure to nanoparticles from toner-based laser printer and photocopier emissions (LPEs) induces airway inflammation and systemic oxidative stress, cytotoxicity, and genotoxicity (such as DNA damage). Recent evidence from human and in vitro studies suggests a strong role for oxidative stress caused by free radicals, such as reactive oxygen species (ROS), in the toxicity of laser printer emissions. However, the amount of ROS generated from laser printer nanoparticle emissions and the relative contribution of various fractions (vapors, organics, metals, and metal oxides) have not been investigated to-date. In this study, we aim to quantify short-lived ROS and H

Engineered nanomaterials (ENMs) used in toners to improve their performance are released in the air during laser printer use. ENMs play an important catalytic role in the breakdown of the toner polymer and subsequent rearrangement of organic compounds as well as in the formation of reactive oxygen species (ROS). Cellular, animal, and human occupational exposure studies have shown that such printer-emitted particles (PEPs) induce inflammation, systemic oxidative stress, and genotoxicity, as well as, increase frequency of coughing, wheezing, and upper airway symptoms, raising concerns about their long-term impact on human health. No safety thresholds or regulatory guidelines currently exist for PEPs. In this study, Sprague-Dawley rats were exposed (by whole-body inhalation) to PEPs 5 h/day for up to 21 days using an exposure platform previously developed by the authors. The control group comprised of an equal number of rats exposed to high-efficiency particulate air (HEPA) filtered air. The PEPs had a mean particle diameter of approximately 45 nm, and a total particle number concentration ranging from 4 to 21 × 105 #/cm3. The maximum total volatile organic compound (tVOCs) concentration was 363.2 ± 162 ppb. The Multiple-Path Particle Dosimetry Model (MPPD) estimated the deposited fraction of PEPs to be around 7, 6 and 21% in the head, tracheobronchial (TB) and alveolar regions, respectively. Analysis of biochemical markers in the nasal and bronchoalveolar lavage fluids (NLF, BALF) of PEPs-exposed animals showed only mild oxidative stress and inflammation. No damage was detected in the histological and chemiluminescence analysis of lung and heart tissues of PEPs-exposed animals. Pro- and anti-inflammatory cytokines and chemokines, such as Interleukin (IL) 1β, IL-12, IL-18, MIP-1α, MIP-2, GRO/KC, and Fractalkine were found to be up-/down-regulated in NLF and BALF of the PEPs-exposed animals. Also, serum biomarkers of oxidative stress and inflammation, such as 8-isoprostane, 4-hydroxynonemal, and Leukotriene B4 were elevated in PEPs-exposed animals. In conclusion, following exposure to PEPs, there was modest lung injury and inflammation in the respiratory tract. Specifically, changes in expression of certain cytokines and chemokines, along with serum levels of 8-isoprostane, were the most significant adverse effects reported following exposure to PEPs.

Additional file 1: Figure S1. TGA temperature-time profile (right ordinate, dashed line), corresponding sample mass (left ordinate) of as-produced (solid lines) and the mass loss normalized to the mass at the end of Step 1. Figure S2. XPS analysis. (a) Si-OH/O-Si-O ratio and total silanol content varying as a function of the combustion enthalpy. (b) Si-OH/O-Si-O ratio as a function of the total silanol. Figure S3. Determining the critical delivered sonication energy of SiO2 NPs. (a) Mean hydrodynamic diameter and (b) polydispersity index as a function of dispersion sonication energy of Wetchem SiO2 NPs, FSP made SiO2 NPs and commercial fumed SiO2 NPs in DI H2O. Figure S4. Fate and transport modeling results for SiO2 NPs. (a) Delivered-to-cell concentration normalized to the administered dose and (b) delivered-to-cell fraction deposited of wet chemistry made silica, FSP made SiO2 NPs and commercial fumed SiO2 NPs in RPMI + 10% (vol/vol) FBS. Solid lines are the fitting curves obtained using eq. 1 and 2. Figure S5. Importance of other modulators in silica NPs effect analyzing RAW264.7 cells. (a, b) short-lived ROS and H2O2 produced by the different SiO2 NPs at a fixed value of silanol content of 150 nmol. (c) Cytotoxicity of different SiO2 NPs at a fixed value of delivered silanol per cell area of 1 × 1014 #/cm2. (d) Viability of different SiO2 NPs at a fixed value of delivered silanol per cell area of 1.5 × 1014 #/cm2. Figure S6. Cytotoxicity (a) and Viability (PrestoBlue assay) (b) measured in SAEC cells. The data represented as function of total silanol delivered per cell area for the three delivered doses used. Data represent an average of three independent experiments performed in triplicate. Figure S7. ROS generation as a measure of oxidative damage (CellROX Green assay) in SAEC cells. After 24-h treatment, ROS generation was measured and data represented as function of total silanol delivered per cell area for the three delivered doses used. Data represent an average of three independent experiments performed in triplicate. Figure S8. Cytotoxicity measured in RAW264.7 cells. The data is represented as function of short life ROS-H2O2 eq. nmol. Data represent an average of three independent experiments performed in triplicate. Table S1. Mean values of the parameters obtained for suspension preparation and colloidal characterization of wet chemistry made silica, FSP made silicas and commercial fumed silica in H2O and RPMI + 10% (vol/vol) FBS. Table S2. The short-lived ROS and H2O2 generated from seven types of silica over the 10–100 μg/mL range. Values have been corrected for sonication and background oxidation of Trolox.

Engineered water nanostructures (EWNS) synthesized utilizing electrospray and ionization of water, have been, recently, shown to be an effective, green, antimicrobial platform for surface and air disinfection, where reactive oxygen species (ROS), generated and encapsulated within the particles during synthesis, were found to be the main inactivation mechanism. Herein, the antimicrobial potency of the EWNS was further enhanced by integrating electrolysis, electrospray and ionization of de-ionized water in the EWNS synthesis process. Detailed physicochemical characterization of these enhanced EWNS (eEWNS) was performed using state-of-the-art analytical methods and has shown that, while both size and charge remain similar to the EWNS (mean diameter of 13 nm and charge of 13 electrons), they possess a three times higher ROS content. The increase of the ROS content as a result of the addition of the electrolysis step before electrospray and ionization led to an increased antimicrobial ability as verified by E. coli inactivation studies using stainless steel coupons. It was shown that a 45-minute exposure to eEWNS resulted in a 4-log reduction as opposed to a 1.9-log reduction when exposed to EWNS. In addition, the eEWNS were assessed for their potency to inactivate natural microbiota (total viable and yeast and mold counts), as well as, inoculated E.coli on the surface of fresh organic blackberries. The results showed a 97% (1.5-log) inactivation of the total viable count, a 99% (2-log) reduction in the yeast and mold count and a 2.5-log reduction of the inoculated E.coli after 45 minutes of exposure, without any visual changes to the fruit. This enhanced antimicrobial activity further underpins the EWNS platform as an effective, dry and chemical free approach suitable for a variety of food safety applications and could be ideal for delicate fresh produce that cannot withstand the classical, wet disinfection treatments.

Typically, a teacher with more positive work values is more capable of handling the teaching jobs. He/she holds a more optimistic attitude toward the educational tasks and devotes more into teaching innovations. Similarly, during the non-formal learning process, a venue worker is analogous to a teacher for school education, his/her job involvement or job burnout conditions also affect the education within a venue. It is thus necessary to investigate the job involvement or job burnout conditions of venue workers. In order to inspect the influence vocational education and work values of venue workers on their job involvement and burnout conditions, 573 venue workers were selected in this study for the investigation by vocational education questionnaire, work values questionnaire, job involvement questionnaire, and job burnout questionnaire. The results are described as follows. 1. Vocational education have a significantly positive influence on job involvement. 2. Vocational education have a significantly positive influence on job burnout. 3. Work values have a significantly positive influence on job involvement. 4. Work values have a significantly positive influence on job burnout. Based on these results, we proposed recommendations accordingly so that the vocational education can bring its effects to the maximum degree and the off-campus studies for the public can be greatly enhanced.

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.

Object The goal of this study was to assess neuroimaging and clinical outcomes in patients harboring brainstem metastases that were treated with the Leksell Gamma Knife. Methods Twenty-eight patients with brainstem metastases (32 lesions: 8 midbrain, 21 pontine, and 3 medullary) were consecutively treated with GKS. The primary cancer diagnoses in this group included 22 cases of lung cancer, 5 cases of breast cancer, and 1 case of rectal cancer. The median age of the patients was 61 years (range 45–83 years). The median treated lesion volume was 0.78 cm3 (range 0.03–5.6 cm3), and the median GKS margin dose was 16 Gy (range 12–20 Gy). Overall survival in these patients was calculated using the Kaplan-Meier method. Results The median survival time was 9 months after GKS (range 2–32 months). Survival was 39.3% at 1 year and 10.7% at 2 years. The tumor control rate in the series was 90.6% (29 of 32 lesions). Development of peritumoral edema occurred in 1 patient after GKS; 4 months after GKS, the edema disappeared. Conclusions Gamma Knife surgery using a median margin dose of 16 Gy is a safe and effective local therapy for patients with brainstem metastases.

Object The goal of this study was to evaluate the efficacy and safety of same-day stereotactic aspiration and Gamma knife surgery (GKS) for cystic intracranial tumors. Methods Between 1996 and 2007, 77 patients harboring cystic intracranial tumors underwent a same-day procedure of MRI-guided cyst aspiration followed by GKS. The diagnoses were metastatic tumor in 43 patients, glial tumor in 12 patients, vestibular schwannoma in 10 patients, craniopharyngioma in 9 patients, and hemangioblastoma in 3 patients. Results An improvement in symptoms was achieved in 68 patients (88.3%) immediately after cyst aspiration. The mean tumor volume in this group of patients was 25.1 cm3 before aspiration and 11.1 cm3 afterward. Hemorrhage during the course of aspiration was encountered in 1 patient. Transient nausea after cyst aspiration developed in 3 patients. There was no treatment-related hematoma, seizure, neurological deficit, or infection. The median follow-up period was 16 months (range 6–108 months). Tumor control was achieved in 50 (80.6%) of 62 patients who participated in follow-up for at least 6 months. Conclusions The same-day stereotactic aspiration and GKS procedure was safe in patients with cystic brain tumors. Prompt symptom relief was obtained after cyst aspiration. The decrease in tumor volume following aspiration made GKS more effective because a higher prescription dose could be administered with a lower possibility of radiation-induced side effects.

Objective To analyze the feasibility and effectiveness of fractionated Gamma Knife surgery (FGKS) for giant pituitary adenomas. Methods From June 2005 to May 2016, 14 patients with giant pituitary adenomas were treated with FGKS, and 10 patients (71%) completed follow-up evaluation. All patients had undergone surgical resection at least once prior to FGKS. The median-volume of the adenomas was 17.6 cm3(range 4.9–61 cm3). Results The median follow-up period was 31.5 months (range 6–58 months). The size of the tumors decreased in 6 patients and remained stable in 4 patients. The visual acuity improved in 1 patient. None of the patients suffered from vision deterioration caused by FGKS. Conclusion FGKS is an effective treatment modality for giant pituitary adenomas in selected patients.

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

Object This study was undertaken to evaluate clinical outcomes and tumor control in patients harboring orbital cavernous hemangiomas (OCHs) that had been diagnosed based on findings of imaging studies and treated by Gamma Knife surgery (GKS). Methods Between 1995 and 2008, 23 patients harboring OCHs that had been diagnosed on the basis of imaging findings were treated using GKS; complete follow-up data are available in all cases. The median treatment volume was 1.5 cm3 (range 0.15–10.10 cm3), the median tumor margin dose was 15 Gy (range 12–20 Gy), and the median follow-up period was 12 months (range 6–120 months). Results A decrease in tumor size was found in 20 patients, and no tumor progression was observed after GKS. Eleven of 14 patients whose visual function had been adversely affected prior to treatment had improved visual acuity at the last assessment. Side effects of the procedure included orbital pain in 3 patients and chemosis in 2 patients. Conclusions In this preliminary experience, GKS proved to be an effective treatment for OCHs diagnosed on the basis of imaging findings. Additional follow-up is necessary, and the long-term side effects of the procedure still need to be determined.

Object The authors evaluated the results they obtained using Gamma Knife surgery (GKS) in patients with orbital tumors. Methods This is a retrospective clinical evaluation of 202 patients with orbital tumors who were treated with GKS between September 1995 and October 2008. The series included 84 men and 118 women with a mean age of 39.5 ± 14.6 years (range 5–85 years). The diagnoses were determined based on pathological analyses in 113 patients and presumed based on characteristic clinical and imaging findings in 89 patients. There were 84 meningiomas, 38 epithelial tumors of the lacrimal gland, 23 schwannomas, 18 malignant choroidal melanomas, 12 optic nerve gliomas, 11 orbital metastases, 10 pseudotumors of the orbit, 3 retinoblastomas, and 3 cases of fibromatosis. The median target volume was 5.4 cm3 (range 0.04–35.6 cm3). The tumor margin dose ranged from 10 to 40 Gy. Results At a median follow-up period of 34.5 ± 14.7 months (range 12–114 months), tumor shrinkage was observed in 118 patients (58.4%) and stable tumor size in 71 patients (35.1%). Regularly scheduled neuroimaging studies demonstrated evidence of tumor progression in only 13 patients (6.4%): 9 of these patients underwent repeated GKS and 4 received surgical treatment. Visual acuity was preserved in 129 patients. Seventy-two patients experienced some degree of improvement in vision. Severe deterioration of visual acuity was found in 18 of 147 patients who had useful vision before treatment. Nineteen patients (9.4%) experienced transient conjunctival edema; no other serious acute side effect was observed. Conclusions Gamma Knife surgery provides an effective management strategy in patients with orbital tumors; it achieves excellent preservation of neurological function and is associated with few treatment-related complications.

Object The goal of this study was to assess the long-term results of Gamma Knife surgery (GKS) in patients harboring an optic nerve sheath meningioma (ONSM). Methods Thirty patients harboring an ONSM were treated with GKS between 1998 and 2003. Gamma Knife surgery was performed as the sole treatment option in 21 of these patients and resection had been performed previously in 9 patients. The mean volume of the tumor at the time of GKS was 3.6 cm3 (range 1.4–9.7 cm3), and the mean prescription peripheral dose was 13.3 Gy (range 10–17 Gy). The mean number of isocenters used to treat these lesions was 8 (range 5–14 isocenters). Results At a median follow-up of 56 months, visual acuity improved in 11 patients, remained stable in 13 patients (including 4 patients who were completely blind before GKS), and deteriorated in 6 patients. Follow-up images were available in all patients and showed tumor regression in 20 patients and stable tumor in 8 patients. Persistent imaging evidence of progression was only present in 2 patients. With the exception of reversible conjunctival edema in 4 cases, no other serious acute side effect was observed. Conclusions Gamma Knife surgery provides long-term tumor control for ONSM. The results of this study add substantial evidence that GKS may definitely become a standard treatment approach in selected cases of ONSM.

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.