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In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air–liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials. [ABSTRACT FROM AUTHOR]

Empirical high-resolution surface wind fields, automatically generated by a weather diagnostic application, the WegenerNet Wind Product Generator (WPG), were intercompared with wind field analysis data from the Integrated Nowcasting through Comprehensive Analysis (INCA) system and with regional climate model wind field data from the Consortium for Small Scale Modeling Model in Climate Mode (CCLM). The INCA analysis fields are available at a horizontal grid spacing of 1 km × 1 km, whereas the CCLM fields are from simulations at a 3 km × 3 km grid. The WPG, developed by , generates diagnostic fields on a high-resolution grid of 100 m × 100 m, using observations from two dense meteorological station networks: the WegenerNet Feldbach Region (FBR), located in a region predominated by a hilly terrain, and its Alpine sister network, the WegenerNet Johnsbachtal (JBT), located in a mountainous region. The wind fields of these different empirical–dynamical modeling approaches were intercompared for thermally induced and strong wind events, using hourly temporal resolutions as supplied by the WPG, with the focus on evaluating spatial differences and displacements between the different datasets. For this comparison, a novel neighborhood-based spatial wind verification methodology based on fractions skill scores (FSSs) is used to estimate the modeling performances. All comparisons show an increasing FSS with increasing neighborhood size. In general, the spatial verification indicates a better statistical agreement for the hilly WegenerNet FBR than for the mountainous WegenerNet JBT. The results for the WegenerNet FBR show a better agreement between INCA and WegenerNet than between CCLM and WegenerNet wind fields, especially for large scales (neighborhoods). In particular, CCLM clearly underperforms in the case of thermally induced wind events. For the JBT region, all spatial comparisons indicate little overlap at small neighborhood sizes, and in general large biases of wind vectors occur between the regional climate model (CCLM) and analysis (INCA) fields and the diagnostic (WegenerNet) reference dataset. Furthermore, grid-point-based error measures were calculated for the same evaluation cases. The statistical agreement, estimated for the vector-mean wind speed and wind directions again show better agreement for the WegenerNet FBR than for the WegenerNet JBT region. A combined examination of all spatial and grid-point-based error measures shows that CCLM with its limited horizontal resolution of 3 km × 3 km, and hence too smoothed an orography, is not able to represent small-scale wind patterns. The results for the JBT region indicate significant biases in the INCA analysis fields, especially for strong wind speed events. Regarding the WegenerNet diagnostic wind fields, the statistics show acceptable performance in the FBR and somewhat overestimated wind speeds for strong wind speed events in the Enns valley of the JBT region. [ABSTRACT FROM AUTHOR]

A weather diagnostic application for automatic generation of gridded wind fields in near-real-time, recently developed by the authors Schlager et al. (2017), is applied to the WegenerNet Johnsbachtal (JBT) meteorological station network. This station network contains 11 meteorological stations at elevations from about 600 to 2200m in a mountainous region in the north of Styria, Austria. The application generates, based on meteorological observations with a temporal resolution of 10 min from the WegenerNet JBT, mean wind and wind gust fields at 10 and 50m height levels with a high spatial resolution of 100m-100m and a temporal resolution of 30 min. These wind field products are automatically stored to the WegenerNet data archives, which also include long-term averaged weather and climate datasets from post-processing. The main purpose of these empirically modeled products is the evaluation of convection-permitting dynamical climate models as well as investigating weather and climate variability on a local scale. The application's performance is evaluated against the observations from meteorological stations for representative weather conditions, for a month including mainly thermally induced wind events (July 2014) and a month with frequently occurring strong wind events (December 2013). The overall statistical agreement, estimated for the vector-mean wind speed, shows a reasonably good modeling performance. Due to the spatially more homogeneous wind speeds and directions for strong wind events in this mountainous region, the results show somewhat better performance for these events. The difference between modeled and observed wind directions depends on the station location, where locations along mountain slopes are particularly challenging. Furthermore, the seasonal statistical agreement was investigated from 5-year climate data of the WegenerNet JBT in comparison to 9- year climate data from the high-density WegenerNet meteorological station network Feldbach Region (FBR) analyzed by Schlager et al. (2017). In general, the 5-year statistical evaluation for the JBT indicates similar performance as the shorter-term evaluations of the two representative months. Because of the denserWegenerNet FBR network, the statistical results show better performance for this station network. The application can now serve as a valuable tool for intercomparison with, and evaluation of, wind fields from highresolution dynamical climate models in both theWegenerNet FBR and JBT regions. [ABSTRACT FROM AUTHOR]

Empirical high-resolution surface wind fields, automatically generated by a weather diagnostic application, the WegenerNet Wind Product Generator (WPG), were intercompared with wind field analysis data from the Integrated Nowcasting through Comprehensive Analysis (INCA) system and with dynamical climate model wind field data from the non-hydrostatic climate model COSMO-CLM. The INCA analysis fields are available at a horizontal grid spacing of 1kmx1km, whereas the COSMO model fields are from simulations at a 3kmx3km grid. The WPG, developed by Schlager et al. (2017, 2018), generates diagnostic fields at a high resolution grid of 100mx100m, using observations from two dense meteorological station networks: The WegenerNet Feldbach Region (FBR) and its alpine sister network, the WegenerNet Johnsbachtal (JBT). The high-density WegenerNet FBR is located in southeastern Styria, Austria, a region predominated by a hilly terrain and small differences in altitude. The network consists of more than 150 meteorological stations. The WegenerNet JBT contains eleven meteorological stations at elevations ranging from about 600m to 2200m in a mountainous region in northern Styria. The wind fields of these different empirical/dynamical modeling approaches were intercompared for thermally induced and strong wind events, using hourly temporal resolutions as supplied by the WPG, with the focus on evaluating spatial differences and displacements between the different datasets. For this comparison, a novel neighborhood-based spatial wind verification methodology based on fractions skill socres (FSS) is used to estimate the modeling performances. All comparisons show an increasing FSS with increasing neighborhood size. In general, the spatial verification indicates a better statistical agreement for the hilly WegenerNet FBR than for the mountainous WegenerNet JBT. The results for the WegenerNet FBR show a better agreement between INCA and WegenerNet than between COSMO and WegenerNet wind fields, especially for large scales (neighborhoods). In particular, COSMO-CLM clearly underperforms in case of thermally induced wind events. For the JBT region, all spatial comparisons indicate little overlap at small neighborhood sizes and in general large biases of wind vectors occur between the dynamical (COSMO) and analysis (INCA) fields and the diagnostic (WegenerNet) reference dataset. Furthermore, gridpoint-based error measures were calculated for the same evaluation cases. The statistical agreement, estimated for the vector-mean wind speed and wind directions show again a better agreement for the WegenerNet FBR than for the WegenerNet JBT region. In general, the difference between modeled and observed wind directions is smaller for strong wind speed events than for thermally induced ones. A combined examination of all spatial and gridpoint-based error measures shows that COSMO-CLM with its limited horizontal resolution of 3kmx3km and hence, a too smoothed orography, is not able to represent small-scale wind patterns. The results for the JBT region indicate that the INCA analysis fields generally overestimate wind speeds in the summit regions. For strong wind speed events the wind speed in the valleys is underestimated by INCA, however. Regarding the WegenerNet diagnostic wind fields, the statistics show decent performance in the FBR and somewhat overestimated wind speeds for strong wind speed events in the Enns valley of the JBT region. [ABSTRACT FROM AUTHOR]

An operational weather diagnostics application for automatic generation of wind fields in near-real time from observations delivered by the high-density WegenerNet meteorological station network in the Feldbach region of Austria is introduced. The purpose of the application is to empirically provide near-surface wind fields of very high spatial and temporal resolution for evaluating convection-permitting climate models as well as investigating weather and climate variability on a local scale. The diagnostic California Meteorological Model (CALMET) is used as the core tool. This model computes 3D wind fields based on observational weather data, a digital elevation model, and land-use categories. The application first produces the required input files from the WegenerNet stations and subsequently runs the CALMET model based on this input. In a third step the modeled wind fields are stored in the WegenerNet data archives every 30 min with a spatial resolution of 100 m × 100 m, while also generating averaged weather and climate products during postprocessing. The performance of the modeling against station observations, for which wind speeds were classified into weak and strong wind speeds, is evaluated and reasonably good results were found for both wind speed classes. The statistical agreement for the vector-mean wind speed is slightly better for weak wind speeds than for strong ones while the difference between modeled and observed wind directions is smaller for strong wind speeds than for weak ones. The application is also a valuable tool for other high-density networks. [ABSTRACT FROM AUTHOR]

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammation-relevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols. [ABSTRACT FROM AUTHOR]

Whereas the characterization of nanomaterials using different analytical techniques is often highly automated and standardized, the sample preparation that precedes it causes a bottleneck in nanomaterial analysis as it is performed manually. Usually, this pretreatment depends on the skills and experience of the analysts. Furthermore, adequate reporting of the sample preparation is often missing. In this overview, some solutions for techniques widely used in nano-analytics to overcome this problem are discussed. Two examples of sample preparation optimization by automation are presented, which demonstrate that this approach is leading to increased analytical confidence. Our first example is motivated by the need to exclude human bias and focuses on the development of automation in sample introduction. To this end, a robotic system has been developed, which can prepare stable and homogeneous nanomaterial suspensions amenable to a variety of well-established analytical methods, such as dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), field-flow fractionation (FFF) or single-particle inductively coupled mass spectrometry (sp-ICP-MS). Our second example addresses biological samples, such as cells exposed to nanomaterials, which are still challenging for reliable analysis. An air–liquid interface has been developed for the exposure of biological samples to nanomaterial-containing aerosols. The system exposes transmission electron microscopy (TEM) grids under reproducible conditions, whilst also allowing characterization of aerosol composition with mass spectrometry. Such an approach enables correlative measurements combining biological with physicochemical analysis. These case studies demonstrate that standardization and automation of sample preparation setups, combined with appropriate measurement processes and data reduction are crucial steps towards more reliable and reproducible data. [ABSTRACT FROM AUTHOR]

Empirical high-resolution (100 m × 100 m) surface wind fields were intercompared withdata from the non-hydrostatic regional climate model COSMO-CLM (3 km resolution) andwith wind field analysis data from the Integrated Nowcasting through ComprehensiveAnalysis (INCA) system (1 km resolution), using hourly temporal resolution (Schlager et al.,2018). The empirical wind fields were generated, using the CALMET diagnostic model, for tworegions with dense meteorological station networks: The WegenerNet Feldbach Region(FBR; Kirchengast et al., 2014) and its alpine sister network, the WegenerNet Johnsbachtal(JBT). The high-density WegenerNet FBR is located in southeastern Styria, Austria, a regionpredominated by a hilly terrain and limited differences in elevations. The network consists of155 meteorological stations, located within an area of about 22 km × 16 km (one station per∼2 km2), observing temperature, humidity, precipitation, wind, soil moisture, and otherparameters, at a temporal resolution of 5-minutes. The WegenerNet JBT is located in amountainous region in northern Styria and contains 11 meteorological stations distributedover an area of about 16 km × 17 km and elevations ranging from about 600 m to2200 m. The focus of the presented work lies on evaluating spatial differences and displacementsbetween the different datasets for thermally induced and strong wind events. For thisintercomparison, a neighborhood-based spatial wind verification methodology, the so-calledWind Fractions Skill Score (WFSS), is used to estimate the modeling performances.Furthermore, gridpoint-based statistical error measures were calculated for the sameevaluation events. The spatial verification indicates a better statistical agreement for the hilly WegenerNetFBR than for the mountainous WegenerNet JBT. The results for the WegenerNet FBR show abetter agreement between INCA and WegenerNet than between COSMO and WegenerNetwind fields, especially for large scales (neighborhoods). In particular, COSMO-CLM clearlyunderperforms in case of thermally induced wind events. For the JBT region, all spatialintercomparisons indicate little overlap at small neighborhood sizes. Considerable biases ofwind vectors occur between INCA and WegenerNet as well as between COSMO and INCA.It is shown that COSMO-CLM, with a limited horizontal resolution of 3 km ×3 km and hence a too smooth orography, is not able to represent small-scale windpatterns.References:Kirchengast, G., T. Kabas, A. Leuprecht, C. Bichler, and H. Truhetz (2014): WegenerNet: Apioneering high-resolution network for monitoring weather and climate. Bull. Amer. Meteor.Soc., 95, 227–242, doi:10.1175/BAMS-D-11-00161.1.Schlager, C., G. Kirchengast, J. Fuchsberger, A. Kann, and H. Truhetz (2018): A spatialevaluation of high-resolution wind fields from empirical and dynamical modeling in hilly andmountainous terrain. Geosci. Model Dev. Discuss., 1–26, doi:10.5194/gmd-2018-238 [ABSTRACT FROM AUTHOR]

Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.

Background: People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments., Objectives: To assess the efficacy and safety of topical treatments for scalp psoriasis., Search Methods: We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials., Selection Criteria: Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis., Data Collection and Analysis: Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high., Main Results: We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments., Authors' Conclusions: The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).