Development and Usability Testing of the Society for Pediatric Anesthesia Pedi Crisis Mobile Application.

When life-threatening, critical events occur in the operating room, the fast-paced, high-distraction atmosphere often leaves little time to think or deliberate about management options. Success depends on applying a team approach to quickly implement well-rehearsed, systematic, evidence-based assessment and treatment protocols. Mobile devices offer resources for readily accessible, easily updatable information that can be invaluable during perioperative critical events. We developed a mobile device version of the Society for Pediatric Anesthesia 26 Pediatric Crisis paper checklists-the Pedi Crisis 2.0 application-as a resource to support clinician responses to pediatric perioperative life-threatening critical events. Human factors expertise and principles were applied to maximize usability, such as by clustering information into themes that clinicians utilize when accessing cognitive aids during critical events. The electronic environment allowed us to feature optional diagnostic support, optimized navigation, weight-based dosing, critical institution-specific phone numbers pertinent to emergency response, and accessibility for those who want larger font sizes. The design and functionality of the application were optimized for clinician use in real time during actual critical events, and it can also be used for self-study or review. Beta usability testing of the application was conducted with a convenience sample of clinicians at 9 institutions in 2 countries and showed that participants were able to find information quickly and as expected. In addition, clinicians rated the application as slightly above "excellent" overall on an established measure, the Systems Usability Scale, which is a 10-item, widely used and validated Likert scale created to assess usability for a variety of situations. The application can be downloaded, at no cost, for iOS devices from the Apple App Store and for Android devices from the Google Play Store. The processes and principles used in its development are readily applicable to the development of future mobile and electronic applications for the field of anesthesiology.

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells.

BACKGROUND: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). RESULTS: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 µg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 µg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 µg/mL MWCNT-HT & ND. CONCLUSIONS: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks.

Profiling mild steel welding processes to reduce fume emissions and costs in the workplace.

To provide quantitative information to choose the best welding processes for minimizing workplace emissions, nine gas metal arc welding (GMAW) processes for mild steel were assessed for fume generation rates, normalized fume generation rates (milligram fume per gram of electrode consumed), and normalized generation rates for elemental manganese, nickel, and iron. Shielded metal arc welding (SMAW) and flux-cored arc-welding (FCAW) processes were also profiled. The fumes were collected quantitatively in an American Welding Society-type fume chamber and weighed, recovered, homogenized, and analyzed by inductively coupled atomic emission spectroscopy for total metals. The processes included GMAW with short circuit, globular transfer, axial spray, pulsed spray, Surface Tension Transfer™, Regulated Metal Deposition™, and Cold Metal Transfer™ (CMT) modes. Flux-cored welding was gas shielded, and SMAW was a single rod type. Results indicate a wide range of fume emission factors for the process variations studied. Fume emission rates per gram of electrode consumed were highest for SMAW (~13 mg fume g(-1) electrode) and lowest for GMAW processes such as pulsed spray (~1.5mg g(-1)) and CMT (~1mg g(-1)). Manganese emission rates per gram of electrode consumed ranged from 0.45 mg g(-1) (SMAW) to 0.08 mg g(-1) (CMT). Nickel emission rates were generally low and ranged from ~0.09 (GMAW short circuit) to 0.004 mg g(-1) (CMT). Iron emission rates ranged from 3.7 (spray-mode GMAW) to 0.49 mg g(-1) (CMT). The processes studied have significantly different costs, and cost factors are presented based on a case study to allow comparisons between processes in specific cost categories. Costs per linear meter of weld were $31.07 (SMAW), $12.37 (GMAW short circuit), and $10.89 (FCAW). Although no single process is the best for minimizing fume emissions and costs while satisfying the weld requirements, there are several processes that can minimize emissions. This study provides information to aid in those choices. Suggestions for overcoming barriers to utilizing new and less hazardous welding processes are also discussed.

Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses.

Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 µg/cm² MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 µm optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels.

An evaluation of welding processes to reduce hexavalent chromium exposures and reduce costs by using better welding techniques.

A group of stainless steel arc welding processes was compared for emission rates of fume and hexavalent chromium, and costs per meter length of weld. The objective was to identify those with minimal emissions and also compare relative labor and consumables costs. The selection included flux-cored arc welding (FCAW), shielded-metal arc welding (SMAW), and multiple gas metal arc welding (GMAW) processes. Using a conical chamber, fumes were collected, and fume generation rates and hexavalent chromium (Cr(6+)) were measured. GMAW processes used were short-circuit (SC) and pulsed-spray modes. Flux-cored welding used gas shielding. Costs were estimated per meter of a 6.3-mm thick horizontal butt weld. Emission rates of Cr(6+) were lowest for GMAW processes and highest for SMAW; several GMAW processes had less than 2% of the SMAW generation rate. Labor and consumable costs for the processes studied were again highest for SMAW, with those of several GMAW types about half that cost. The results show that use of any of the GMAW processes (and flux-cored welding) could substantially reduce fume and Cr(6+) emissions, and greatly reduce costs relative to SMAW.

Size Distribution and Estimated Respiratory Deposition of Total Chromium, Hexavalent Chromium, Manganese, and Nickel in Gas Metal Arc Welding Fume Aerosols.

A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc welding (GMAW) fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified welding-fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel fumes was 9.2% (6.8%). For stainless steel fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 µm. Total Cr and Ni presented an additional fraction <0.03 µm. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio (p-value D 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ∼25%. The sites of principal deposition were the head airways (7-10%) and the alveolar region (11-14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%).

Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions.

BACKGROUND: Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. METHODS: The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. RESULTS: The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. CONCLUSIONS: Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to investigate the health effect of biodiesel as well as efficiency of DOC or other exhaust aftertreatment systems.

Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells.

With the development of nanotechnology, there is a tremendous growth of the application of nanomaterials, which increases the risk of human exposure to these nanomaterials through inhalation, ingestion, and dermal penetration. Among different types of nanoparticles, single-walled carbon nanotubes (SWCNT) with extremely small size (1 nm in diameter) exhibit extraordinary properties and offer possibilities to create materials with astounding features. Since the release of nanoparticles in an enclosed environment is of great concern, a study of possible genotoxic effects is important. Our previous data showed that pharyngeal aspiration of SWCNT elicited pulmonary effects in C57BL/6 mice that was promoted by a robust, acute inflammatory reaction with early onset resulting in progressive interstitial fibrogenic response and the formation of granulomas. In the present study, the genotoxic potential of SWCNT was evaluated in vitro. The genotoxic effects of nanoparticles were examined using three different test systems: the comet assay and micronucleus (MN) test in a lung fibroblast (V79) cell line, and the Salmonella gene mutation assay in strains YG1024/YG1029. Cytotoxicity tests showed loss of viability in a concentration- and time-dependent manner after exposure of cells to SWCNT. Results from the comet assay demonstrated the induction of DNA damage after only 3 h of incubation with 96 microg/cm2 of SWCNT. The MN test indicated some but not significant micronucleus induction by SWCNT in the V79 cell line at the highest concentrations tested. With two different strains of Salmonella typhimurium, no mutations were found following SWCNT exposure.

Diesel exhaust particulate matter dispersed in a phospholipid surfactant induces chromosomal aberrations and micronuclei but not 6-thioguanine-resistant gene mutation in V79 cells.

Diesel exhaust particulate material (DPM) was assayed for induction of chromosomal aberrations (CA), micronucleus (MN) formation, and 6-thioguanine-resistant (TG9 gene mutation in V79 cells as a dispersion in dipalmitoyl phosphatidylcholine (DPPC) in physiological saline, a simulated pulmonary surfactant. Filter-collected automobile DPM provided for the study was not organic solvent extracted, but was directly mixed into DPPC in saline dispersion as a model of pulmonary surfactant conditioning of a soot particle depositing in a lung alveolus. A statistically significant difference was found between treated and control groups at all concentrations tested in a CA assay. Assay for MN induction also gave a positive response: Above 50 microg/ml, the frequencies of micronucleated cells (MNC) were about 2 times higher than those in the control group. The forward gene mutation assay did not show a positive response when cells were treated with up to 136 microg DPM/ml for 24 h, as dispersion in DPPC in saline. Some comparison assays were run on direct dispersions of the DPM into dimethyl sulfoxide, with results equivalent to those seen with a DPPC-saline preparation: DPM in dimethyl sulfoxide (DMSO) was positive for MN induction but was negative for forward gene mutation in V79 cells. The positive clastogenicity results are consistent with other studies of DPM dispersed into DPPC-saline surfactant that have shown activity in mammalian cells for sister chromatid exchange, unscheduled DNA synthesis, and MN induction. The forward gene mutation negative results are consistent with studies of that assay applied to V79 cells challenged with DPM solvent extract.

Characterization of hard metal dusts from sintering and detonation coating processes and comparative hydroxyl radical production.

Dust samples from sintering and detonation coating hard-metal processes were characterized, compared, and contrasted for morphology, composition, and generation of hydroxyl radicals. Inhalation of respirable hard-metal (sintered carbide) dusts from hard-metal processes is known to cause fibrotic and asthmatic lung disease. Scanning electron microscopy/energy-dispersive X-ray analysis was used for morphology, composition, and elemental distribution. An electron spin resonance (ESR) spin trapping technique was used to detect hydroxyl radical generation. Samples were incubated with air-saturated buffer solutions containing a spin trap and analyzed by ESR for the presence of *OH in solution. Postdetonation coating samples often had surface contamination of Co on the WC particles, as shown by elemental mapping of individual particles; this was not evident in predetonation samples or unsintered materials in this study. ESR measurements show that both detonation-gun materials were capable of generating *OH , while the WC, cobalt, and presintered mixture did not produce detectable amounts of *OH radicals. The DMPO/*OH adduct formation was apparently facilitated by Fe-mediated reactions for predetonation dusts, and by Fe-mediated site-specific reactions for postdetonation dusts. The overspray materials from the detonation-gun process produced 9-fold more *OH radicals than the predetonation coating mixture. Overall, this study indicates there are substantial differences between postdetonation materials and both predetonation and unsintered hard-metal process materials with respect to morphology, elemental distribution, and *OH radical generation reactions and that these differences may be important in the toxic potential of those materials.

Cis-4-[(18)F]fluoro-L-proline PET imaging of pulmonary fibrosis in a rabbit model.

UNLABELLED: A fluorinated analog of proline amino acid, cis-4-[(18)F]fluoro-L-proline (FP), was tested for potential use in PET for detection and evaluation of pulmonary response to respirable crystalline silica. The purpose of the study was to determine whether PET imaging with FP is sensitive for detection of pulmonary fibrosis. METHODS: Experimental silicosis was produced in rabbits by airway instillation of 300 mg respirable silica in 0.9% sterile saline; control rabbits received only saline. After 1, 2, 4, or 5 mo, animals were injected with 37 MBq (1 mCi) FP, and imaged in sets of 2 to 3 in a PET scanner using a dynamic scanning protocol over a 3-h period. Each imaging set contained at least 1 control rabbit. FP uptake in each lung was scored from 0 to 5 (PET score) by consensus of 3 readers blinded to animals' exposure status. Animals were humanely killed 2 d after the last imaging, and tissue sections from each lung lobe were graded from 0 to 5 by histopathology examination (histopathology score) for severity and distribution of fibrosis. RESULTS: Silicotic animals had significantly higher (P < 0.05) PET scores at each time point than did control animals. Repeated-measures ANOVA showed significant differences in PET scores between silicotic and control animals for the total lung field, but there were no statistically significant time trends for either group. Presence of fibrosis (i.e., histopathology score > 1) showed a significant association with elevated PET score (i.e., PET score > 1) using Fisher's exact test (P < 0.05). PET scores also showed excellent predictive ability, as all animals (18/18) with fibrosis also had elevated PET scores, and 95% (18/19) of animals with PET scores > 1 showed evidence of fibrosis. Localization of activity to specific lung areas was less exact, perhaps due in part to the small animal size for the resolution of the clinical PET imager used. PET scores were elevated (>1) for 67% (10/15) of silicotic right lungs and 75% (12/16) of silicotic left lungs; fibrosis scores > 1 were measured in 91% (10/11) of right lungs with PET scores > 1, and in 92% (12/13) of such left lungs. CONCLUSION: The FP tracer provided sensitive and specific identification of silicotic animals in early stages of the disease. This suggests that FP PET imaging has the potential sensitivity to detect active fibrosis in silicosis and other lung diseases. Additional studies are needed to determine the specificity of the FP tracer for fibrosis versus inflammatory processes.