Inflammatory myofibroblastic tumor of the mesentery with a SQSTM1::ALK fusion responding to alectinib.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an ultra-rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK-targeting agents based on fusion partner is limited. CASE: A 30-year-old female sought emergency care after onset of abdominal and lower back pain in 2019. Computed tomography (CT) demonstrated a cystic, mesenteric mass within the pelvis measuring up to 8.9 cm. Complete laparoscopic excision of the mass from the mesentery of the right colon and terminal ileum was performed. Pathologic assessment revealed IMT with a fusion between sequestosome 1 and ALK (SQSTM1::ALK), described in only two other cases of IMT. Four months after surgery, CT revealed multi-focal, unresectable disease recurrence. She was referred to the University of Washington/Fred Hutchinson Cancer Center and placed on therapy with alectinib, after which she experienced a partial response. Three years after IMT recurrence, disease remains under control. CONCLUSION: This is the third reported case of IMT associated with the novel SQSTM1::ALK fusion protein, and the second treated with alectinib. Treatment with the ALK inhibitor alectinib appears to be active in this setting.

Prolonged laparoscopic surgery is associated with an increased risk of vertebral disc prolapse.

The benefits of laparoscopic surgery to the patient are well recognised, however it is more physically demanding on the surgeon. A survey was sent to members of the British Society of Gynaecological Endoscopy to ascertain musculoskeletal symptoms and vertebral disc prolapse thought to occur as a result of undertaking laparoscopic surgery. A total of 19 (15%) participants were diagnosed with a vertebral disc prolapse, for which one-third needed definitive treatment. There was a statistically significant association with length of practice and numbers of hours worked per week, with the risk of disc prolapse. There was a multitude of other musculoskeletal symptoms reported. These findings suggest that gynaecological laparoscopic surgery carries a high personal health risk to the surgeon, which is likely to increase as the capability and superiority of laparoscopic techniques develop. There is an urgent need to explore further the ergonomic impact of laparoscopic work to enable improvements to be made.

Enhancements to the JET poloidally scanning vacuum ultraviolet∕visible spectrometers.

Enhancements to the JET poloidally scanning spectrometers are presented, which will aid the exploitation of the recently installed ITER-like wall in JET. They include the installation of visible filter∕photomultiplier tube assemblies and spectrometers and the replacement of large rotating mirrors in the JET vacuum with small oscillating mirrors outside. The upgrade has resulted in a more robust and reliable diagnostic than before, which is described. Drifts in the mirror angle reconstructed from quadrature encoder signals are found, a reference signal being required. The use of the small scanning mirrors necessitated the inclusion of focusing mirrors to maintain throughput into the vacuum ultraviolet spectrometers. The mirror design has taken account of the extreme sensitivity of the focusing to the grazing angle of incidence, an aspect of importance in the design of grazing incidence focusing components on future machines, such as ITER. The visible system has been absolutely calibrated using an in-vessel light source.

Air quality model evaluation data for organics. 6. C3-C24 organic acids.

The atmospheric concentrations of 47 carboxylic acids in the semivolatile and particle phases are quantified in the Los Angeles area, as part of a larger study of the vapor-phase, semivolatile, and particle-phase organic compounds. Variations in the spatial and temporal distributions of acid concentrations are analyzed to determine whether atmospheric formation or primary emissions are responsible for the observed levels. Relatively low molecular weight aliphatic dicarboxylic acids (e.g., butanedioic acid, hexanedioic acid, and propanedioic acid) and some n-alkanoic acids (e.g., n-octanoic acid and n-nonanoic acid) are found at an offshore sampling location at levels comparable to urban area concentrations indicating that these compounds or their atmospheric precursors may be derived from long-range transport or natural background sources. Some aromatic carboxylic acids (e.g., benzoic acid and 1,2-benzenedicarboxylic acid) have spatial and temporal distributions suggesting that formation from anthropogenic emissions of gaseous precursors dominates their atmospheric concentrations. Additionally, the distributions of aliphatic carboxylic acid concentrations known to be emitted from primary sources (e.g., hexadecanoic acid and octadecanoic acid) are consistent with direct emissions as the dominant source of these compounds.

Emissions of size-segregated aerosols from on-road vehicles in the Caldecott tunnel.

Particulate matter emissions from the California in-use vehicle fleet were measured as 37,500 vehicles traveled through two bores of the Caldecott Tunnel located in the San Francisco Bay area. Microorifice cascade impactors and filter-based samplers were used to determine the particle chemical composition as a function of particle size. Ammonia emissions from the vehicle fleet were measured as well. Concentrations of aerosol mass, organic carbon, elemental carbon, sulfate ion, nitrate ion, and ammonium ion, as well as 13 elements are reported. The particle mass distribution peaks in the particle size range 0.1-0.18 microm aerodynamic diameter (Da). Elemental carbon and organic matter were the largest components of particle mass in all the size ranges studied. The Caldecott Tunnel bores studied include one which carries light-duty vehicle traffic and one which carries a mixture of light- and heavy-duty vehicle traffic. From experiments conducted in both bores, estimates are made of the size distribution and chemical composition of particulate matter emissions extrapolated to the 100% light-duty and 100% heavy-duty vehicle fleets. The heavy-duty vehicle fleet emitted 1285 +/- 237 mg of fine particulate matter (Da < 1.9 microm)/kg of C contained in the fuel burned (corresponding to approximately 430 +/- 79 mg/km driven). Light-duty vehicles emitted less than 85 +/- 6 mg/kg of C in the fuel burned (corresponding to less than approximately 5.5 +/- 0.4 mg/km driven). Emissions of gas-phase ammonia in the Caldecott Tunnel were measured to be 194 and 267 mg/L of gasoline-equivalent fuel burned in the tunnel. The ammonia emissions are attributed to automobiles that were equipped with 3-way catalysts and operating fuel rich.

Quantification of ATOFMS data by multivariate methods.

Aerosol time-of-flight mass spectrometry (ATOFMS) is capable of measuring the sizes and chemical compositions of individual polydisperse aerosol particles in real time. A qualitative estimate of the particle composition is acquired in the form of a mass spectrum that must be subsequently interpreted in order to draw conclusions regarding atmospheric relevance. The actual problem involves developing a calibration that allows the mass spectral data to be transformed into estimates of the composition of the atmospheric aerosol. A properly calibrated ATOFMS system should be able to quantitatively determine atmospheric concentrations of various species. Ideally, it would be able to accomplish this more rapidly, accurately, with higher size and time resolution, and at a far lower marginal cost than the manual sampling methods that are currently employed. Attempts have already been made at using ATOFMS and similar techniques to extract the bulk chemical species concentration present in an ensemble of particles. This study represents the use of a multivariate calibration method, two-dimensional partial least-squares analysis, for calibrating single-particle mass spectral data. The method presented here is far less labor-intensive than the univariate methods attempted to date and allows for less observer bias. Because of the labor savings, this is also the most comprehensive calibration performed to date, resulting in the quantification of 44 different chemical species.

Chemical characterization of fine particle emissions from fireplace combustion of woods grown in the northeastern United States.

A series of source tests was conducted to determine the chemical composition of fine particle emissions from the fireplace combustion of six species of woods grown in the northeastern United States: red maple, northern red oak, paper birch, eastern white pine, eastern hemlock, and balsam fir. Results include fine particle emission rates for total mass, organic and elemental carbon, ionic species, elemental species including potassium, and over 250 specific organic compounds. The data are intended for use in source-apportionment studies that utilize particulate organic compounds as source-specific tracers. The cellulose pyrolysis product levoglucosan was quantified in each of the wood smokes studied and is thus a good candidate as a molecular tracer for wood combustion in general. Differences in emission rates of specific substituted phenols and resin acids can be used to distinguish between the smoke produced when burning hardwoods versus softwoods. Certain organic compounds, such as betulin from paper birch combustion and juvabione and dehydrojuvabione from balsam fir combustion, are unique to those species and can potentially be utilized to trace particulate emissions back to a specific geographical region where those individual tree species are used for firewood.

Highly polar organic compounds present in wood smoke and in the ambient atmosphere.

Fine particulate matter emitted during wood combustion is known to contribute a significant fraction of the total fine aerosol concentration in the atmosphere of both urban and rural areas. In the present study, additional organic compounds that may act as wood smoke tracers in the atmosphere are sought. Polar organic compounds in wood smoke fine particulate matter are converted to their trimethylsilyl derivatives and analyzed by gas chromatography/mass spectrometry. Silylation enables the detection of n-alkanols, plant sterols, and a number of compounds derived from wood lignin that have not previously been reported in wood smoke samples, as well as levoglucosan and related sugar anhydrides formed during the combustion of cellulose. The concentrations of these compounds measured in source emissions are compared to the concentrations in atmospheric fine particle samples collected at a rural background site and at two urban sites in California's San Joaquin Valley. On the basis of this analysis, the sugar anhydrides galactosan and mannosan can be listed along with levoglucosan as being among the most abundant organic compounds detected in all samples.

Source apportionment of fine particulate matter by clustering single-particle data: tests of receptor model accuracy.

The source apportionment accuracy of a neural network algorithm (ART-2a) is tested on the basis of its application to synthetic single-particle data generated by a source-oriented aerosol processes trajectory model that simulates particle emission, transport, and chemical reactions in the atmosphere. ART-2a successfully groups particles from the majority of sources actually present, when given complete data on ambient particle composition at monitoring sites located near the emission sources. As particles age in the atmosphere, accumulation of gas-to-particle conversion products can act to disguise the source of the primary core of the particles. When ART-2a is applied to synthetic single-particle data that are modified to simulate the biases in aerosol time-of-flight mass spectrometry (ATOFMS) measurements, best results are obtained using the ATOFMS dual ion operating mode that simultaneously yields both positive and negative ion mass spectra. The results of this study suggest that the use of continuous single-particle measurements coupled with neural network algorithms can significantly improve the time resolution of particulate matter source apportionment.

Measurement of emissions from air pollution sources. 3. C1-C29 organic compounds from fireplace combustion of wood.

Organic compound emission rates for volatile organic compounds (VOC), gas-phase semivolatile organic compounds, and particle-phase organic compounds are measured from residential fireplace combustion of wood. Firewood from a conifer tree (pine) and from two deciduous trees (oak and eucalyptus) is burned to determine organic compound emissions profiles for each wood type including the distribution of the alkanes, alkenes, aromatics, polycyclic aromatic hydrocarbons (PAH), phenol and substituted phenols, guaiacol and substituted guaiacol, syringol and substituted syringols, carbonyls, alkanoic acids, resin acids, and levoglucosan. Levoglucosan is the major constituent in the fine particulate emissions from all three wood types, contributing 18-30% of the fine particulate organic compound emissions. Guaiacol (2-methoxyphenol), and guaiacols with additional substituents at position 4 on the molecule, and resin acids are emitted in significant quantities from pine wood combustion. Syringol (2,6-dimethoxyphenol) and syringols with additional substituents at position 4 on the molecule are emitted in large amounts from oak and eucalyptus firewood combustion, but these compounds are not detected in the emissions from pine wood combustion. Syringol and most of the substituted syringols are found to be semivolatile compounds that are present in both the gas and particle phases, but two substituted syringols that have not been previously quantified in wood smoke emissions, propionylsyringol and butyrylsyringol, are found exclusively in the particle phase and can be used to help trace hardwood smoke particles in the atmosphere. Benzene, ethene, and acetylene are often used as tracers for motor vehicle exhaust in the urban atmosphere. The contribution of wood smoke to the ambient concentrations of benzene, ethene, and acetylene could lead to an overestimate of the contribution of motor vehicle tailpipe exhaust to atmospheric VOC concentrations.

The Indian Ocean experiment: widespread air pollution from South and Southeast Asia.

The Indian Ocean Experiment (INDOEX) was an international, multiplatform field campaign to measure long-range transport of air pollution from South and Southeast Asia toward the Indian Ocean during the dry monsoon season in January to March 1999. Surprisingly high pollution levels were observed over the entire northern Indian Ocean toward the Intertropical Convergence Zone at about 6 degrees S. We show that agricultural burning and especially biofuel use enhance carbon monoxide concentrations. Fossil fuel combustion and biomass burning cause a high aerosol loading. The growing pollution in this region gives rise to extensive air quality degradation with local, regional, and global implications, including a reduction of the oxidizing power of the atmosphere.

Modeling the long-term frequency distribution of regional ozone concentrations using synthetic meteorology.

A new method is developed to generate the meteorological input fields required for use with photochemical airshed models that seek to predict the effect of pollutant emissions on the long-term frequency distribution of peak O3 concentrations. Instead of using meteorological fields derived from interpolation of direct weather observations, this method uses synthetically generated meteorological data. These synthetic meteorological fields are created by first constructing a semi-Markov process that generates a time series of large-scale synoptic weather conditions that statistically resemble the occurrence and persistence of synoptic weather patterns during specific months of the year. Then for each day within each synoptic weather category, local weather variables indicative of the meteorological potential for ozone formation are drawn from the approximated joint distribution of the summation of three pressure gradients across the airshed and the 850 mb temperature measured in the early morning. The synthetic initial conditions are combined with boundary values that are extracted from historical days that match the chosen synoptic class, temperature, and pressure gradient values as closely as possible for use in a prognostic mesoscale meteorological model. The prognostic mesoscale meteorological model generates the meteorological input fields necessary for the photochemical airshed model. The airshed model driven by synthetically generated meteorological data is executed for a 31 day period that statistically resembles weather during the month of August in Southern California using pollutant emissions data from the year 1987. The procedure produced a frequency of occurrence of peak 8 h average ozone concentrations that compared well both to that produced by the deterministic model as well as to the O3 concentrations observed over the August months of the years 1984-1990.

Effect of emissions control programs on visibility in southern California.

A new method for the analysis and display of the effect of emissions controls on visibility is applied to conditions in southern California. An advanced mechanistic air quality model that represents airborne particles as a source-oriented external mixture first is used to track emissions source contributions to the size distribution and chemical composition of airborne particles at Claremont, CA, under heavy smog conditions. The resulting description of the aerosol is used in a Mie scattering calculation to determine the magnitude and particle size dependence of light scattering and absorption in the atmosphere. The resulting light scattering and absorption coefficient values are supplied to an image processing-based visibility model that creates full color representations of the appearance of the local terrain in the presence of the specified level of air pollution based on satellite-generated landscape images. By linking these models, a direct connection is established between source emissions and resulting visual air quality. The composite modeling system then is used to studythe effectthat different emissions control strategies would have on visibility in southern California. An aggressive program of 92 specific emissions control measures that include primary particle controls plus controls on reactive gases that act as secondary aerosol precursors would more than double visual range at Claremont under the 1987 historical conditions studied. Synthetic landscape images show that the mountains to the north of Claremont that are not visible at a range of 10 km under base-case conditions would be visible if the emissions controls described above were applied.

Trends in fine particle concentration and chemical composition in southern California.

Airborne fine particle mass concentrations in Southern California have declined in recent years. Trends in sulfate and elemental carbon (EC) particle concentrations over the period 1982-1993 are consistent with this overall improvement in air quality and help to confirm some of the reasons for the changes that are seen. Fine particle sulfate concentrations have declined as a strict sulfur oxides (SOx) emission control program adopted in 1978 was implemented over time. Fine particle elemental (black) carbon concentrations have declined over a period when newer diesel engines and improved diesel fuels have been introduced into the vehicle fleet. Organic aerosol concentrations have not declined as rapidly as the EC particle concentrations, despite the fact that catalyst-equipped cars having lower particle emission rates were introduced into the vehicle fleet alongside the diesel engine improvements mentioned above. This situation is consistent with the growth in population and vehicle miles traveled in the air basin over time. Fine particle ammonium nitrate in the Los Angeles area atmosphere contributes more than half of the fine aerosol mass concentration on the highest concentration days of the year, emphasizing both the need for accurate aerosol nitrate measurements and the likely importance of deliberate control of aerosol nitrate as a part of any serious further fine particle control program for the Los Angeles area.

Randomized double-blind study of the clinical duration and efficacy of Nesacaine-MPF 2% and 3% in peribulbar anesthesia.

PURPOSE: To compare 2 commercially available concentrations of Nesacaine-MPF (2-chloroprocaine) to determine the time to onset of adequate motor blockade, the quality of surgical anesthesia, and the duration of motor blockade in the extraocular muscles after peribulbar anesthesia for cataract surgery. SETTING: Tampa Eye and Specialty Surgery Center, Tampa, Florida, USA. METHODS: This double-blind, randomized, single-center study comprised 40 patients scheduled to receive peribulbar anesthesia before cataract surgery. Patients were given 5 mL of Nesacaine-MPF 2% or 3% before surgery. Beginning at the end of the injection, assessments of ocular and eyelid movement were made every 2 minutes until adequate motor blockade was achieved or 25 minutes elapsed. Ocular assessments were made immediately after completion of surgery, 60 minutes after the end of the initial injection, and at 15 minute intervals thereafter until full recovery. Assessments of the quality of anesthesia achieved by the patient during surgery were made by the surgeon. RESULTS: The 3% solution provided significantly faster onset of surgical anesthesia than the 2% solution (mean 3.9 minutes +/- 2.2 [SD] versus 6.0 +/- 3.6 minutes) (P = .02) but also required more time for recovery from anesthesia (98.9 +/- 18.7 minutes versus 84.8 +/- 20.6 minutes) (P = .02). All patients had adequate surgical anesthesia. Duration of ocular motor function was brief enough so that all patients could be sent home without an eye patch. Both concentrations were safe for use in this procedure. CONCLUSION: Both Nesacaine-MPF 2% and 3% produced safe and effective peribulbar anesthesia in all patients; however, the 3% solution provided better duration of clinical anesthesia.

The Magnitude of Bias in the Measurement of PM25 Arising from Volatilization of Particulate Nitrate from Teflon Filters.

Because the Federal Reference Method for PM25 specifies the collection of ambient particles on Teflon filters, we have examined the loss of a known volatile species, particulate nitrate, during sampling. Data are presented from two studies in southern California for which parallel samples were collected by different methods. Differences in collected nitrate are modeled using an evaporation model based on the work of Zhang and McMurry. The average nitrate obtained from sampling with Teflon filters was 28% lower on average than that measured by denuded nylon filters. In contrast, cascade impactor samples were within 5% of the denuded nylon filter on average. A simple model is presented that accounts for the particulate nitrate loss from Teflon filters either by scavenging nitric acid and ammonia in the sampler inlet or by heating the filter substrate during sampling. The observed magnitude of loss is explained by any of the following situations: (1) 100% nitric acid and ammonia vapor loss in the inlet, (2) 5 °C heating of the filter substrate above ambient temperature during sampling, or (3) a combination of these factors, such as 50% vapor loss in the inlet and 3 °C heating of the filter.

Prioritizing testing of organic compounds detected as gas phase air pollutants: structure-activity study for human contact allergens.

Organic compounds that are used or generated anthropogenically in large quantities in cities can be identified through their presence in the urban atmosphere and in air pollutant source emissions. Compounds identified by this method were screened to evaluate their potential to act as contact allergens. The CASE and MULTICASE computer programs, which are based on the detection of structure-activity relationships (SAR), were used to evaluate this potential. These relationships first are determined by comparing chemical structures to biological activity within a learning set comprised of 458 compounds, each of which had been tested experimentally in human trials for its sensitization potential. Using the information contained in this learning set, CASE and MULTICASE predicted the activity of 238 compounds found in the atmosphere for their ability to act as contact allergens. The analysis finds that 21 of 238 compounds are predicted to be active contact allergens (probability >0.5), with potencies ranging from mild to very strong. The compounds come from chemical classes that include chlorinated aromatics and chlorinated hydrocarbons, N-containing compounds, phenols, alkenes, and an S-containing compound. Using the measured airborne concentrations or emission rates of these compounds as an indication of the extent of their use, together with their predicted potencies, provides an efficient method to prioritize the experimental assessment of contact sensitization of untested organic compounds that can be detected as air pollutants.

Particulate air pollution: possible relevance in asthma.

The relative importance of air pollution in the pathogenesis of bronchial asthma has been of interest for several decades. Numerous studies on the role of gaseous air pollution containing ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide have been published. Very little attention has been focused on the role of respirable particles in the causation of asthma. In this article we summarize some of our ongoing investigations into the sources and composition of airborne particles in the Los Angeles and Pasadena atmosphere, including the search for biologically active particles that may induce asthma attacks. If is found that the urban atmosphere contains not only combustion-derived particles from diesel engine exhaust and gasoline-powered motor vehicle exhaust, but also particles formed from biological starting materials including plant debris, cigarette smoke, wood smoke, and meat smoke as well as tire debris containing some natural rubber and paved road dust. Paved road dust is a very complex mixture of particles including garden soil, tire dust, plant fragments, redeposited atmospheric particles of all types, and pollen fragments presumably ground up by passing traffic. We have shown previously that latex allergen can be extracted from tire dust, from roadside dust, and from respirable air samples taken at Los Angeles and Long Beach. At present, work is underway to identify the larger range of allergens that may be contributed by the entrainment of paved road dust into the atmosphere. The possible importance of pollen fragments present in paved road dust in very small particle sizes is discussed as well as their potential relevance in asthma.

Latex allergens in tire dust and airborne particles.

The prevalence and severity of latex allergy has increased dramatically in the last 15 years due to exposure to natural rubber products. Although historically this health risk has been elevated in hospital personnel and patients, a recent survey has indicated a significant potential risk for the general population. To obtain a wide-spread source for latex exposure, we have considered tire debris. We have searched for the presence of latex allergens in passenger car and truck tire tread, in debris deposited from the atmosphere near a freeway, and in airborne particulate matter samples representative of the entire year 1993 at two sites in the Los Angeles basin (California). After extraction of the samples with phosphate buffered saline, a modified-ELISA inhibition assay was used to measure relative allergen potency and Western blot analyses were used to identify latex allergens. The inhibition studies with the human IgE latex assay revealed inhibition by the tire tread source samples and ambient freeway dust, as well as by control latex sap and latex glove extracts. Levels of extractable latex allergen per unit of protein extracted were about two orders of magnitude lower for tire tread as compared to latex gloves. Western blot analyses using binding of human IgE from latex-sensitive patients showed a band at 34-36 kDa in all tire and ambient samples. Long Beach and Los Angeles, California, air samples showed four additional bands between 50 and 135 kDa. Alternative Western blot analyses using rabbit IgG raised against latex proteins showed a broad band at 30-50 kDa in all samples, with additional bands in the urban air samples similar to the IgE results. A latex cross-reactive material was identified in mountain cedar. In conclusion, the latex allergens or latex cross-reactive material present in sedimented and airborne particulate material, derived from tire debris, and generated by heavy urban vehicle traffic could be important factors in producing latex allergy and asthma symptoms associated with air pollution particles.

Seasonal and spatial variation of the bacterial mutagenicity of fine organic aerosol in southern california.

The bacterial mutagenicity of a set of 1993 urban particulate air pollution samples is examined using the Salmonella typhimurium TM677 forward mutation assay. Amibent fine particulate samples were collected for 24 hr every sixth day throughout 1993 at four urban sites, including Long Beach, central Los Angeles, Azusa, and Rubidoux, California, and at an upwind background site on San Nicolas Island. Long Beach and central Los Angeles are congested urban areas where air quality is dominated by fresh emissions from air pollution sources; Azuasa and Rubidoux are located farther downwind and receive transported air pollutants plus increased quantities of the products of atmospheric chemical reactions. Fine aerosol samples from Long Beach and Los Angeles show a pronounced seasonal variation in bacterial mutagenicity per cubic meter of- ambient air, with maximum in the winter and a minimum in the summer. The down-wind smog receptor site at Rubidoux shows peak mutagenicity (with postmitochondrial supernatant but no peak without postmitochondrial supernatant) during the September-October periods when direct transport from upwind sources can be expected. At most sites the mutagenicity per microgram of organic carbon from the aerosol is not obviously higher during the summer photochemical smog period than during the colder months. Significant spatial variation in bacterial mutagenicity is observed: mutagenicity per cubic meter of ambient air, on average, is more than an order of magnitude lower at San Nicolas Island than within the urban area. The highest mutagenicity values per microgram of organics supplied to the assay are found at the most congested urban sites at central Los Angeles and Long Beach. The highest annual average values of mutagenicity per cubic meter of air sampled occur at central Los Angeles. These findings stress the importance of proximity to sources of direct emissions of bacterial mutagens and imply that if important mutagen-forming atmospheric reactions occur, they likely occur in the winter and spring seasons as well as the photochemically more active summer and early fall periods.