The Effect of Flame-Retardant Additives DDM-DOPO and Graphene on Flame Propagation over Glass-Fiber-Reinforced Epoxy Resin under the Influence of External Thermal Radiation.

The flammability of various materials used in industry is an important issue in the modern world. This work is devoted to the study of the effect of flame retardants, graphene and DDM-DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide-4,4'-diamino-diphenyl methane), on the flammability of glass-fiber-reinforced epoxy resin (GFRER). Samples were made without additives and with additives of fire retardants: graphene and DDM-DOPO in various proportions. To study the flammability of the samples, standard flammability tests were carried out, such as thermogravimetric analysis, the limiting oxygen index (LOI) test, and cone calorimetry. In addition, in order to test the effectiveness of fire retardants under real fire conditions, for the first time, the thermal structure of downward flame propagation over GFRER composites was measured using thin thermocouples. For the first time, the measured thermal structure of the flame was compared with the results of numerical simulations of flame propagation over GFRER.

Mechanisms of the Action of Fire-Retardants on Reducing the Flammability of Certain Classes of Polymers and Glass-Reinforced Plastics Based on the Study of Their Combustion.

In the present review, using an integrated approach based on the experimental and theoretical study of the processes of thermal decomposition and combustion of practically important polymers, such as polymethyl methacrylate, polyethylene, and glass-fiber-reinforced epoxy resin, the features of the mechanism for reducing the combustibility of these materials with phosphorus-containing flame-retardants (FR), as well as graphene, are identified. A set of original experimental methods was developed and applied that make it possible to study the kinetics of thermal decomposition and the thermal and chemical structure of the flames of the studied materials, including those with FR additives, as well as to measure the flame propagation velocity, the mass burning rate, and the heat fluxes from the flame on the surface of a material. Numerical models were developed and tested to describe the key parameters of the flames of the studied polymeric materials. An analysis of the experimental and numerical simulation data presented showed that the main effect of phosphorus-containing fire-retardants on reducing the combustibility of these materials is associated with the inhibition of combustion processes in the gas phase, and the effect of adding graphene manifests itself in both gas and condensed phases.

The Influence of Flame Retardants on Combustion of Glass Fiber-Reinforced Epoxy Resin.

For the first time, next to the flammability tests (LOI, UL-94 HB, VBB, TGA), experimental tests and computer simulation have been conducted on the flame spread and combustion of glass fiber-reinforced epoxy resins (GFRER) with 6% graphene and 6% DDM-DOPO flame-retardant additives. The downward rates of flame spread (ROS) in opposed flow with oxidizer and the upward ROS along GFRER composites have been first measured as well as the distribution of temperature over the combustion surface of the composites with flame-retardant additives and without them. The LOI and UL-94 HB tests showed a reduction in the flammability of GFRER when flame retardants were added and predicted a higher effectiveness of DDM-DOPO compared to graphene. Adding DDM-DOPO resulted in increasing the rate of formation of the volatile pyrolysis products and their yield, indicating, together with the other data obtained, the gas phase mechanism of the flame retardant's action. Adding graphene resulted in an increase in the soot release on the burning surface and an increase in the amount of non-volatile pyrolysis products on the burning surface, reducing the amount of fuel that participated in the oxidation reactions in the gas phase. The developed numerical combustion model for GFRER with a DDM-DOPO additive, based on the action of DDM-DOPO as a flame retardant acting in the gas phase, satisfactorily predicts the effect of this flame retardant on the reduction in downward ROS over GFRER for 45-50% oxygen concentrations. The developed model for GFRER with graphene additive, based on a reduction in the amount of fuel and increase in the amount of incombustible volatile pyrolysis products when graphene is added, predicts with good accuracy downward ROS over GFRER depending on oxygen concentration.

Experimental and Numerical Study of Downward Flame Spread over Glass-Fiber-Reinforced Epoxy Resin.

For the first time, a comprehensive study of downward flame spread over glass-fiber-reinforced epoxy resin (GFRER) slabs in oxidizer flow has been carried out experimentally and numerically. Microthermocouples were used to measure the temperature profiles on the solid fuel's surface and in the flame, and a video camera was used to measure the rate of flame spread (ROS). The ROS was found to be linearly dependent on the oxygen concentration, to be inversely proportional to the slab thickness and not to depend on the direction of the flame spread over the slab. The absence of the influence of the forced oxidizing flow velocity and the weak influence of the GFRER pyrolysis kinetics on the ROS were observed. For the first time, a numerical model of flame spread over reinforced material with thermal conductivity anisotropy was developed on the basis of a coupled 'gas-solid' heat and mass transfer model, using modifications of the OpenFOAM open-source code. The sensitivity analysis of the model showed that the thermal conductivity in the normal direction to the GFRER surface had a much greater effect on the ROS than the thermal conductivity along the direction of flame propagation. The numerical results show good agreement with the experimental data on the dependences of the ROS on oxygen concentration, slab thickness and the N2/O2 mixture flow velocity, as well as temperature distributions on the fuel surface, the maximum flame temperatures and the flame zone length.

Novel approach to constructing laser ionization elemental time-of-flight mass spectrometer.

The main advantages of laser sampling are associated with following features: sample preparations as well as consumables are not needed, low risk of sample contamination, good spatial resolution. In mass spectrometry, high laser irradiance can be used for both ablation and ionization processes. The method is especially profitable in time-of-flight mass spectrometry. A new principle of constructing laser ionization time-of-flight mass spectrometer based on wedge-shaped ion mirrors and the absence of electrostatic ion acceleration before mass analysis is discussed. Among advantages of the analyzer there are ability to provide temporal focusing of ions in a wide energy range (±20%), compactness of the analyzer, and minimization of the requirements for power supplies. The approach is expected to be profitable for standardless elemental analysis of solid samples, which should be possible at laser irradiation power density more than 3 × 109 W/cm2 that ensures complete ionization of all elements in a laser plasma. The analytical signal of each element is formed as the sum of the signals for all charge states and the energy scan of the mass spectra is provided.

A computer model of comprehensive modeling of the laser time-of-flight analyzer.

This article offers a new approach to computer modeling of time-of-flight analyzers of mass spectrometers. The main feature of the model is comprehensive tracking of the processes from the laser plasma generation until the final stage, on which the isotopic or elemental composition is determined for the analyzed solid sample. Apart from usual models based on SIMION-8 3D or similar software, this article proposes fundamentally new modeling stages. These stages are (1) generation and spread of laser plasma, (2) formation of the ion packages, (3) ion detection, and (4) formation and processing of the analytical signals. In order to provide consistent modeling of all the stages, special software units were developed. Program control of the analyzer ion optics (electrodes voltages) allows scan of mass spectra by ion energy. Additional complex of the programs provides simulation of mass spectra digitization, summation of digitized mass spectra for a wide range of variable parameters, and consideration of the discriminatory effects. According to the data, the software calculates ion-optical characteristics of the analyzer and the analytical parameters of measurement results.

Secukinumab improves patient-reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo-controlled clinical trials.

BACKGROUND: Secukinumab is a human interleukin-17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The objective of this analysis was to measure the treatment response on psoriasis-related itching, pain, and scaling via the Psoriasis Symptom Diary (PSD)(©). METHODS: ERASURE (n = 738) and FIXTURE (n = 1306) were double-blind, multicenter phase 3 studies in adults randomized to secukinumab (300, 150 mg, n = 1144) or placebo (n = 574) (administered at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks) or a biologic active control (FIXTURE only). Patient-reported itching, pain, and scaling were assessed during the first 12 weeks of treatment using the PSD. The results reported here are limited to subjects in the secukinumab and placebo treatment groups who completed the PSD. The proportions of subjects achieving prespecified responses (improvement:reduction of at least 2.2 points for itching, 2.2 points for pain, or 2.3 points for scaling) were compared for secukinumab versus placebo. RESULTS: Overall, 39% of subjects completed the PSD at baseline and Week 12 (n = 453 secukinumab; 225 placebo). Subjects treated with secukinumab achieved significantly greater improvements in itching, pain, and scaling at Week 12 versus placebo (all P < 0.0001) and had significantly greater proportions of itching, pain, and scaling responders at Week 12 versus placebo (all P < 0.05). CONCLUSION: Secukinumab significantly improves patient-reported itching, pain, and scaling in adults with moderate to severe psoriasis compared with placebo.

Letter: The formation of ion packages with ultrashort duration in laser ion source.

A new approach to the formation of ultrashort laser ion packages in the ion source of time-of-flight (TOF) mass spectrometer for elemental analysis is described. This is achieved by installing a wedge-shaped reflector with special correcting plates. The reflector provides time and space focusing of the ion packages. Such time focusing allows to reduce the ion package duration up to 1 ns. The proposed approach allows more than order of magnitude increase in the resolution of the laser TOF mass spectrometer with an axially symmetric electrostatic analyzer to 10,000-13,000. In this Letter the theoretical calculations justifying the proposed method are presented.

Letter: Compact analyzer for a laser time-of-flight mass spectrometer.

Aspects of a new type of laser time-of-flight mass spectrometer are described in this letter. It is based on a wedge-shaped reflecting mirror and is used as an ion analyzer. The analyzer provides time focusing by both energy and a divergence angle of ions. Time focusing of good quality is acquired in the energy range of ±20% of the average ion energy, which is, at least, two times wider than the energy range of the known ion optical systems for similar applications. The mass resolution of the analyzer is ~600, while overall dimensions are very small (10 × 10 × 5 cm).

Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study.

Secukinumab, a fully human anti-IL-17A monoclonal antibody, neutralizes IL-17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate-to-severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52-week, double-blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI-111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co-primary endpoints (Week 12) were ≥75% improvement in psoriasis area-and-severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5-point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12-week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate-to-severe plaque psoriasis in the Japanese patients.

Secukinumab in plaque psoriasis--results of two phase 3 trials.

BACKGROUND: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). RESULTS: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).

Analysis of new synthetic drugs by ion mobility time-of-flight mass spectrometry.

Characteristic ion mobility mass spectrometry data, reduced mobility, and limits of detection (signal-to-noise ratio = 3) were determined for six synthetic drugs and cocaine by ion mobility time-of-flight mass spectrometry (IM-TOF-MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The studied synthetic illicit drugs recently appeared on the recreational drug market as designer drugs and were methylone, 4-MEC (4'-methylethcathinone), 3,4-MDPV (3,4-methylenedioxypyrovalerone), JWH-210 [4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone], JWH-250 [2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone], and JWH-203 [1-pentyl-3-(2'-chlorophenylacetyl) indole]. Absolute reduced mobilities in nitrogen were 1.35, 1.28, 1.41, 1.30, 1.18, 0.98, 1.09, and 1.07 cm2V(-1)s(-1), for methylone [M-H]+, methylone [M+H]+, 4-MEC [M-H]+, 4-MEC [M+H]+, 3,4-MDPV [M+H]+, JWH-210 [M+H]+, JWH-250 [M+H]+, and JWH-203 [M+H]+, respectively. Selected illicit drugs are easily identified by IM-TOF-MS during a 100s analysis. Relative Limits of detection ranged from 4 to 400 nM are demonstrated for these compounds. Such relative limits of detection correspond to 14 pg to 2 ng absolute limits of detection. Better detection limits are obtained in APCI mode for all the illicit drugs except cocaine. ESI mode was found to be preferable for the IM-TOF-MS detection of cocaine at trace levels. A single sample analysis is completed in an order of magnitude less time than that for conventional liquid chromatography/mass spectrometry approach. The application allows one to consider IM-TOF-MS as a good candidate for a method to determine quickly the recently surfaced designer drugs marketed on the internet as "bath salts," "spice," and "herbal blends".

Development of an atmospheric pressure ion mobility spectrometer-mass spectrometer with an orthogonal acceleration electrostatic sector TOF mass analyzer.

Recently developed ion mobility mass spectrometer is described. The instrument is based on a drift tube ion mobility spectrometer and an orthogonal acceleration electrostatic sector time-of-flight mass analyzer. Data collection is performed using a specially developed fast ADC-based recorder that allows real-time data integration in an interval between 3 and 100 s. Primary tests were done with positive ion electrospray. The tests have shown obtaining 100 ion mobility resolving power and 2000 mass resolving power. Obtained for 2,6-di-tert-butylpyridine in electrosprayed liquid samples during 100 s analysis and full IMS/MS data collection mode were 4 nM relative limits of detection and a 1 pg absolute limit of detection (S/N=3). Characteristic ion mobility/mass distributions were recorded for selected antibiotics, including amoxicillin, ampicillin, lomefloxacin, and ofloxacin. At studied conditions, lomefloxacin forms only a protonated molecule-producing reduced ion mobility peak at 1.082 cm(2)/(V s). Both amoxicillin and ampicillin produce [M + H](+), [M + CH3OH + H](+), and [M + CH3CN + H](+). Amoxicillin shows two peaks at 0.909 cm(2)/(V s) and 0.905 cm(2)/(V s). Ampicillin shows one peak at 0.945 cm(2)/(V s). Intensity of protonated methanol containing cluster for both ampicillin and amoxicillin has a clear tendency to rise with sample keeping time. Ofloxacin produces two peaks in the ion mobility distribution. A lower ion mobility peak at 1.051 cm(2)/(V s) is shown to be formed by [M + H](+) ions. A higher ion mobility peak appearing for samples kept more than 48 h is shown to be formed by both [M + H](+) ion and a component identified as the [M + 2H + M](+2) cluster. The cluster probably partly dissociates in the interface producing the [M + H](+) ion.

Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study.

BACKGROUND: Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain. METHODS: ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m) were randomized to everolimus with CNI elimination (n=127) or CNI minimization (n=144), or continued CNI unchanged (controls, n=123) to assess the effect on measured GFR at month 24 after randomization. RESULTS: Renal function was stable in all groups to month 24. Mean measured GFR at month 24, the primary endpoint, was 48.0±22.0 mL/min/1.73 m, 46.6±21.1 mL/min/1.73 m, and 46.0±20.4 mL/min/1.73 m in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m, 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m, 95% CI -3.88 to 5.07, P=0.79) versus controls at month 24 were nonsignificant that is, the primary endpoint was not met. No efficacy endpoint differed significantly between groups. Post hoc analyses showed that patients with baseline creatinine clearance (CrCl) more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination versus controls (difference 11.4 mL/min/1.73 m, 95% CI 2.1 to 20.8 mL/min/1.73 m, P=0.017). Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs. CNI elimination; P=0.020 vs. CNI minimization). CONCLUSION: Conversion to everolimus with CNI elimination or minimization a mean of 5.6 years after kidney transplantation had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with CrCl more than 50 mL/min may benefit from a change in therapy more than 6 months after renal transplantation.

Three-dimensional EIT imaging of breast tissues: system design and clinical testing.

Results of development and testing of the new medical imaging system are described. The system uses a planar array consisting of 256 electrodes and enables obtaining images of the three-dimensional conductivity distribution in regions below the skin's surface up to several centimeters deep. The developed measuring system and image reconstruction algorithm can be used for breast tissue imaging and diagnostics, in particular for malignant tumor detection. Examples of tomographic images obtained in vivo during clinical tests are presented. The mammary gland, being an organ-target, alters at the background with such physiological events as menstrual cycle, pregnancy, lactation, and postmenopause. The objectives of this paper include estimation of the possibilities of electrical impedance mammography for investigation of mammary glands' state among women with different hormonal status. We found that electrical impedance mammograms from different groups had clear visual distinctions and statistically significant differences in mammary glands' conductivity. Our data on conductivity distribution in the mammary gland during different physiological periods will allow us to use it as normal values in the future, to continue this research on mammary glands with different pathology.

Rathayibacter caricis sp. nov. and Rathayibacter festucae sp. nov., isolated from the phyllosphere of Carex sp. and the leaf gall induced by the nematode Anguina graminis on Festuca rubra L., respectively.

Two novel species, Rathayibacter caricis sp. nov. (type strain VKM Ac-1799T = UCM Ac-618T) and Rathayibacter festucae sp. nov. (type strain VKM Ac-1390T UCM Ac-619T), are proposed for two coryneform actinomycetes found in the phyllosphere of Carex sp. and in the leaf gall induced by the plant-parasitic nematode Anguina graminis on Festuca rubra L., respectively. The strains of the novel species are typical of the genus Rathayibacter in their chemotaxonomic characteristics and fall into the Rathayibacter 16S rDNA phylogenetic cluster. They belong to two separate genomic species and differ markedly from current validly described species of Rathayibacter at the phenotypic level. The most striking feature differentiating Rathayibacter caricis sp. nov. from other species of the genus is the presence of fucose in its cell wall and Rathayibacter festucae sp. nov. can be easily recognized among other yellow-pigmented rathayibacters because of its rose-orange-coloured colonies.