Characterization of mechanisms and processes controlling groundwater salinization in coastal semi-arid area using hydrochemical and isotopic investigations (Essaouira basin, Morocco)

Abstract

The aquifer system of Essaouira basin is recognized as one of the most important aquifers in Morocco. The purpose of this study is to highlight the origin and the mechanisms responsible for the salinization of this aquifer system, thus based on the two hydrogeochemical and isotopic approaches. The results indicate that the central and downstream parts are dominated by the facies Cl-Ca-Mg and SO₄-Ca-Mg with the dominance of the first facies, while the facies Cl-Ca-Mg, SO₄-Ca-Mg, and HCO₃-Ca-Mg dominate the upstream part with the dominance of the list facies. Hydrochemical approach shows that the groundwater mineralization in the study area is controlled by (i) the ion exchange phenomenon, under the marine intrusion and (ii) the dissolution of carbonate minerals (calcite, dolomite, and aragonite) and evaporate minerals (halite, gypsum, and anhydrite). High levels of NO₃ would come from domestic pollutants, including livestock waste during water withdrawal. The isotopic method shows (i) aquifers recharge in the study area is provided by Atlantic precipitation without significant evaporation, (ii) the presence of recent water (after nuclear tests) and other (before nuclear tests), and (iii) various recharge altitudes from 300 to 1150 m asl. However, this investigation provides a foundation for effective groundwater management and effective mitigation of aquifer impacts.

Response to C‐reactive protein as an individual prognostic marker in oral cancer: practical considerations

Clinical Otolaryngology, EarlyView.

C‐reactive protein as an individual prognostic marker in oral cancer: Practical considerations

Clinical Otolaryngology, EarlyView.

Modeling of sediment transport in a saltwater lake with supplemental sandy freshwater

Abstract

Considering the highly complex flow structure of saltwater lakes during freshwater supplementation, a three-dimensional numerical model was developed to simulate suspended sediment transport in saltwater lakes. The model was validated using measurements of the salinity and sediment concentration during a pumping test at Yamdrok Lake. The simulation results were in quantitative agreement with the measured data. The observed and simulated results also indicated that the wind stress and vertical salinity gradient have a significant influence on salinity and sediment transport in a saltwater lake. The validated model was then used to predict and analyze the contributions of wind, the supplement flow rate and salinity stratification to the sediment transport process in Yamdrok Lake during continuous river water supplementation. The simulation results showed that after the sandy river water was continuously discharged into the saltwater lake, the lateral diffusion trends of the sediment exhibited three stages: linear growth in the inflow direction, logarithmic growth in the wind direction, and stabilization. Furthermore, wind was the dominant factor in driving the lake flow pattern and sediment transport. Specifically, wind can effectively reduce the area of the sediment diffusion zone by increasing the lateral sediment carrying and dilution capacities. The effect of inflow on the lake current is negligible, but the extent of the sediment turbidity zone mainly depends on the inflow. Reducing the inflow discharge can decrease the area of the sediment turbidity zone to proportions that far exceed the proportions of inflow discharge reductions. In addition, the high-salinity lake water can support the supplemented freshwater via buoyancy forces, which weaken vertical mixing and sediment settlement and increase lake currents and sediment diffusion near the surface.

Assessment of trophic status of the northeastern Mediterranean coastal waters: eutrophication classification tools revisited

Abstract

The Eastern Mediterranean and its Cilician Basin offshore waters have oligotrophic features with low nutrient concentrations, low primary production, and high water transparency. However, the wide shelf area of the Cilician Basin is subject to contaminated river inflows with enhanced nutrient loads and direct discharges of urban wastewaters of southern Turkey, leading to develop local eutrophic/mesotrophic conditions in the inner sites of Mersin and Iskenderun Bays on the Cilician Basin. For the assessment of changing trophic status of the coastal and the bay water bodies under anthropogenic pressures since the 1980s, five extensive field studies were performed in summer and winter periods of 2014, 2015, and 2016. Physical and eutrophication-related biochemical parameters (salinity, temperature, Secchi Disk Depth, nutrients, dissolved oxygen, chlorophyll-a) were measured at 65 stations in different water bodies occupying the Northeastern (NE) Mediterranean coastal, offshore areas and bays. The collected data sets were used in scaling the trophic status of the visited water bodies of NE Mediterranean coastal, offshore areas and semi-enclosed bays, using novel classification tools of Trophic Index (TRIX), Eutrophication Index (E.I.), chl-a, and HELCOM Eutrophication Assessment Tool (HEAT), developed by different experts for highly productive seas. These tools, which can successfully classify highly productive coastal water masses under human pressures, and their sensitivities have been tested for scaling of the current trophic status of the NE Mediterranean coastal water bodies being subject to human pressures. The scaling results of classical TRIX, E.I., and chl-a indices in the NE Mediterranean water masses are not sensitive enough to differentiate mesotrophic and eutrophic water bodies because these indices principally assume to have higher concentrations of eutrophication-related parameters in the least effected (reference) water bodies. The HEAT tool, which uses a site-specific "reference value" for each eutrophication-indicator, has allowed us to produce more reliable and sensitive scaling of the current trophic status of the NE Mediterranean shelf areas, even though we used only the "reference values" derived from the composite data sets. The results of the indices were compared with the HEAT tool and the actual status was assessed from observations, indicating revision requirements of the multi-metric classification tools. For this goal, scales of natural (oligotrophic) and anthropogenic (eutrophic) levels of eutrophication indicators should be determined at a sub-basin scale using long-term site-specific observations in the NE Mediterranean. The revised scale ranges of TRIX for oligotrophic, mesotrophic, and eutrophic water bodies of Mersin Bay are in line with ranges of TRIX classification tool proposed for Aegean Sea waters, which can be used to assess trophic status of the entire Eastern Mediterranean and Aegean coastal seas (surface salinity > 37.5) having oligotrophic properties in the offshore waters.

PAH and PCB contamination in the sediments of the Venice Lagoon (Italy) before the installation of the MOSE flood defence works

Abstract

Contamination from polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the shallow water areas of the Venice Lagoon (415 km²) was investigated in the surface (0–5 cm) and sub-surface (5–10 cm) sediments by collecting cores from 380 sites. The concentrations of 14 PAHs (USEPA priority pollutants) and seven PCB indicator congeners were analysed with high-performance liquid chromatography (HPLC) and capillary gas chromatography (GC), respectively. PAH and PCB concentrations ranged from 2.75 to 9980 ng g⁻¹ d.w. and from 0.01 to 60.1 ng g⁻¹ d.w., respectively. Their concentrations never exceeded the probable effect level (PEL) stipulated in the respective quality guidelines. In addition, the average total PAH levels expressed as B[a]P toxicity equivalents (total TEQ) were lower in the sediments of the Venice Lagoon than in other literature-reported zones in the Mediterranean. PAH profiles and ratios showed that they originated not only largely from high-temperature pyrolytic processes attributable primarily to the burning of fossil fuels but also partly from petroleum spillage. Comparison of tetra-to-hepta PCB congeners enabled the PCB profiles observed in the lagoon environment to be characterised as Aroclor 1254 and 1260 (1:1). Compared to other marine coastal areas and harbours in the Mediterranean, the Venice Lagoon sediments showed a low mean value but a wide range of concentrations. The estimation of PAH and PCB inventories indicated the low contribution of atmospheric deposition relative to local sources.

Characterization and mechanism of copper biosorption by a highly copper-resistant fungal strain isolated from copper-polluted acidic orchard soil

Abstract

In this paper, a highly copper-resistant fungal strain NT-1 was characterized by morphological, physiological, biochemical, and molecular biological techniques. Physiological response to Cu(II) stress, effects of environmental factors on Cu(II) biosorption, as well as mechanisms of Cu(II) biosorption by strain NT-1 were also investigated in this study. The results showed that NT-1 belonged to the genus Gibberella, which exhibited high tolerance to both acidic conditions and Cu(II) contamination in the environment. High concentrations of copper stress inhibited the growth of NT-1 to various degrees, leading to the decreases in mycelial biomass and colony diameter, as well as changes in morphology. Under optimal conditions (initial copper concentration: 200 mg L⁻¹, temperature 28 °C, pH 5.0, and inoculum dose 10%), the maximum copper removal percentage from solution through culture of strain NT-1 within 5 days reached up to 45.5%. The biosorption of Cu(II) by NT-1 conformed to quasi-second-order kinetics and Langmuir isothermal adsorption model and was confirmed to be a monolayer adsorption process dominated by surface adsorption. The binding of NT-1 to Cu(II) was mainly achieved by forming polydentate complexes with carboxylate and amide group through covalent interactions and forming Cu-nitrogen-containing heterocyclic complexes via Cu(II)-π interaction. The results of this study provide a new fungal resource and key parameters influencing growth and copper removal capacity of the strain for developing an effective bioremediation strategy for copper-contaminated acidic orchard soils.

Think A-Head Campaign of Image Gently: Shared Decision-Making in Pediatric Head Trauma [EDITORIALS]

Morphology-Specific Discrimination between MS White Matter Lesions and Benign White Matter Hyperintensities Using Ultra-High-Field MRI [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Recently published North American Imaging in Multiple Sclerosis guidelines call for derivation of a specific radiologic definition of MS WM lesions and mimics. The purpose of this study was to use SWI and magnetization-prepared FLAIR images for sensitive differentiation of MS from benign WM lesions using the morphologic characteristics of WM lesions.

MATERIALS AND METHODS:

Seventeen patients with relapsing-remitting MS and 18 healthy control subjects were enrolled retrospectively. For each subject, FLAIR and multiecho gradient-echo images were acquired using 7T MR imaging. Optimized postprocessing was used to generate single-slice SWI of cerebral veins. SWI/FLAIR images were registered, and 3 trained readers performed lesion assessment. Morphology, location of lesions, and the time required for assessment were recorded. Analyses were performed on 3 different pools: 1) lesions of >3 mm, 2) nonconfluent lesions of >3 mm, and 3) nonconfluent lesions of >3 mm with no or a single central vein.

RESULTS:

The SWI/FLAIR acquisition and processing protocol enabled effective assessment of central veins and hypointense rims in WM lesions. Assessment of nonconfluent lesions with ≥1 central vein enabled the most specific and sensitive differentiation of patients with MS from controls. A threshold of 67% perivenous WM lesions separated patients with MS from controls with a sensitivity of 94% and specificity of 100%. Lesion assessment took an average of 12 minutes 10 seconds and 4 minutes 33 seconds for patients with MS and control subjects, respectively.

CONCLUSIONS:

Nonconfluent lesions of >3 mm with ≥1 central vein were the most sensitive and specific differentiators between patients with MS and control subjects.

C1 Posterior Arch Flare Point: A Useful Landmark for Fluoroscopically Guided C1-2 Puncture [SPINE]

BACKGROUND AND PURPOSE:

The C1–2 intrathecal puncture is routinely performed when lumbar puncture is not feasible. Usage has steadily decreased in part because of the perceived high risk of injury to the cervical cord. Up to this point, vague fluoroscopic guidelines have been used, creating uncertainty about the actual needle location relative to the spinal cord. We present a novel osseous landmark to aid in C1–2 intrathecal puncture, corresponding to the posterior spinal cord margin on lateral fluoroscopic views. This landmark, which we have termed the "flare point," represents the triangular "flaring" of the posterior C1 arch at its junction with the anterior arch.

MATERIALS AND METHODS:

Cervical spine CT myelograms were reviewed. High-resolution axial images were reformatted into the sagittal plane, and maximum-intensity-projection images were created to simulate a lateral fluoroscopic view. Tangential lines were drawn along the superior cortices of the anterior and posterior C1 arches, with the point of intersection used to approximate the flare point. Chart review was performed for all C1–2 punctures using the flare point technique in the past 3 years.

RESULTS:

Forty-two cervical myelograms were reviewed. The average flare point was 0.2 ± 0.5 mm posterior to the dorsal spinal cord margin. In 37/42 subjects, the flare point was localized posterior to the spinal cord. Targeting by means of the flare point was used in 16 C1–2 punctures without complications.

CONCLUSIONS:

The C1 posterior arch flare point accurately approximates the dorsal spinal cord margin on myelography. Targeting between the flare point and the spinolaminar line, at the mid-C1–2 interspace, allows safe and optimal needle positioning.

A quantum theory investigation on atmospheric oxidation mechanisms of acrylic acid by OH radical and its implication for atmospheric chemistry

Abstract

The hydroxyl radical, as the most important oxidant, controls the removal of some volatile organic compounds (VOCs) in the atmosphere. In this work, the atmospheric oxidation processes of acrylic acid by OH radical have been investigated by density functional theory (DFT). The energetic routes of the reaction of CH₂CHCOOH with OH radical have been calculated accurately at the CCSD(T)/cc-pVTZ//M06-2X/6-311++G(d,p) level. It is implicated that the oxidation has five elementary reaction pathways mostly hinging on how hydroxyl radical approaches to the carbon skeleton of acrylic acid. The atmospheric degradation mechanisms of the CH₂CHCOOH by OH radical are the formation of reactive intermediates IM1 and IM2. Meanwhile, the further oxidation mechanisms of IM1 and IM2 by O₃ and NO are also investigated. The rate coefficients have been computed using tight transition state theory of the variflex code. The calculated rate coefficient is 2.3 × 10⁻¹¹ cm³ molecule⁻¹ s⁻¹ at standard pressure and 298 K, which is very close to the laboratory data (1.75 ± 0.47 × 10⁻¹¹ cm³ molecule⁻¹ s⁻¹). Moreover, the atmospheric lifetime of acrylic acid is about 6 h at 298 K and 1 atm, implying that the fast sinks of acrylic acid by hydroxyl radical.

Aporrectodea caliginosa , a relevant earthworm species for a posteriori pesticide risk assessment: current knowledge and recommendations for culture and experimental design

Abstract

Ecotoxicological tests with earthworms are widely used and are mandatory for the risk assessment of pesticides prior to registration and commercial use. The current model species for standardized tests is Eisenia fetida or Eisenia andrei. However, these species are absent from agricultural soils and often less sensitive to pesticides than other earthworm species found in mineral soils. To move towards a better assessment of pesticide effects on non-target organisms, there is a need to perform a posteriori tests using relevant species. The endogeic species Aporrectodea caliginosa (Savigny, 1826) is representative of cultivated fields in temperate regions and is suggested as a relevant model test species. After providing information on its taxonomy, biology, and ecology, we reviewed current knowledge concerning its sensitivity towards pesticides. Moreover, we highlighted research gaps and promising perspectives. Finally, advice and recommendations are given for the establishment of laboratory cultures and experiments using this soil-dwelling earthworm species.

The effects of rhenium accumulation on Indian mustard

Abstract

Rhenium (Re) is one of Earth's scarcest and more largely scattered elements, with an estimate concentration of 0.4–0.6 μg kg⁻¹ in the upper crust. Still, considerable concentrations of bioavailable ReO₄⁻ ions are often found, particularly in copper-molybdenum mines, where their uptake by plants of these regions has been reported. Yet, the impact of Re on plants remains a question mark, as the only available knowledge derives from a limited investigation carried out over 60 years ago. The aim of this study was to evaluate the ecophysiological response of Brassica juncea, a species known to endure and accumulate various metals, to a broad range of Re concentrations. B. juncea plants were allowed to grow and on a substrate amended with KReO₄ to attain soil Re levels ranging from 0 to 80 mg kg⁻¹. Plants were collected 45 days after sowing for analysis. The results have shown that greater Re levels reduce growth, photosynthetic activity, soluble carbohydrate mobilization, and protein contents, and increase the plant's oxidative stress (anthocyanins, H₂O₂, lipid peroxidation) and corresponding response (ascorbic acid, superoxide dismutase activity). Nevertheless, B. juncea exhibited a remarkable ability to endure and uptake Re, featuring shoot Re concentrations that ranged from 1615 to 24,987 mg kg⁻¹ among the 5 and 80 mg kg⁻¹ treatments.

Comparative study of mercury(II) species removal onto naked and modified magnetic chitosan flakes coated ethylenediaminetetraacetic-disodium: kinetic and thermodynamic modeling

Abstract

This comparative study investigates pre-concentration/separation procedure for the magnetic solid phase extraction of Hg(II) species by a new green materials: naked magnetic chitosan flakes coated Fe₃O₄ micro-particles (NMCFs) and magnetic chitosan flakes coated Fe₃O₄ micro-particles embedded ethylenediaminetetraacetic-disodium (MCFs-EDTA-Na₂) in a batch process. The sorption procedure was optimized by using model solutions containing mercury(II) ions in chloride medium. The influence of experimental parameters like pH, time reaction, initial Hg(II) concentration, and ionic strength was investigated. The SEM micrograph indicates a good dispersion of magnetite micro-particles onto chitosan flakes. The FTIR spectrum reveals that EDTA-Na₂ moieties have been successfully cross-linked onto magnetic chitosan flakes. Vibration magneto-metric measurements confirm the paramagnetic (without remanence) behavior of NMCFs and MCFs-EDTA-Na₂. The experimental sorption data show that Hg(II) ions extraction yield decreases in acidic medium in both NMCFs and MCFs-EDTA-Na₂. The found optimum pH values are near 4.5 using NMCFs and 4.7 when the Hg(II) ion sorption occurs onto MCFs-EDTA-Na₂ micro-particles. The results also showed that Hg(II) ion sorption kinetic was very fast at the initial stage of contact time. The maximal sorption capacity was found to be 454 ± 13 mg g⁻¹, under optimum conditions, using NMCFs and 495 ± 14 mg g⁻¹ when MCFs-EDTA-Na₂ was used.

Effects of exogenous salicylic acid and pH on pathogenicity of biotrophy-associated secreted protein 1 (BAS1)-overexpressing strain, Magnaporthe oryzae

Abstract

Abiotic stress can influence the interactions between a pathogen and its host. In this paper, we analyzed the effects of salicylic acid (SA) and pH on the morphological development and pathogenicity of Magnaporthe oryzae, the pathogen that causes rice (Oryza sativa) blast. A strain of rice blast that overexpresses biotrophy-associated secreted protein 1 (BAS1) and a wild-type (WT) strain were pretreated with different levels of pH and different concentrations of SA to analyze M. oryzae colony growth, sporulation, spore germination, dry weight of hypha, and appressorium formation. Disease incidence and the expression of defense-related genes in infected rice were analyzed after pretreatment with pH 5.00 or pH 8.00 and 200 μM SA. The results showed that both SA and pH had some influence on morphological development, including sporulation and appressorium formation of the BAS1-overexpression strain. In the 200 μM SA pretreatment, there was a lower incidence of disease and higher expression levels of the rice defense-related genes PR1a, PAL, HSP90, and PR5 on leaves inoculated with the BAS1-overexpession strain compared with the WT strain, whereas, LOX2 appeared to be downregulated in the BAS1-overexpession strain compared with the WT. In both pH treatments, disease incidence and expression of HSP90 were higher and the expression of PR1a and PR10a and LOX2 and PAL was lower in leaves inoculated with the BAS1-overexpression strain compared with leaves inoculated with the WT strain. We conclude that SA and pH affect morphological development of the BAS1-overexpression blast strain, but that these factors have little influence on the pathogenicity of the strain, indicating that BAS1-overexpression may have enhanced the tolerance of this rice blast strain to abiotic stressors. This work suggests new molecular mechanisms that exogenous SA and pH affect the interactions between M. oryzae and rice.

Augmentation and eversion of lips without injections: the lip peel

The Elite Facial Surgery Practice: Development and Management

Histopathological analysis of carbaryl-induced toxicity in the spleen of Levantine frog, Pelophylax bedriagae (Anura: Ranidae)

Abstract

This study describes the histopathological effects of carbaryl in the spleen of Levantine frog, Pelophylax bedriage. Due to its primary role in immune system, it is important to research the toxic effects of pesticides, which play an important role in environmental pollution, on spleen. To that end, adult frogs were exposed to carbaryl for 96 h. Experimental groups contained low dose, (0.05 mg/g), medium dose (0.1 mg/g) and high dose (0.2 mg/g). After following exposure to carbaryl, the frogs were euthanised and dissected. In low-dose group, there were no important changes in spleen tissue. In medium-dose group, prominence in haemorrhage just below the capsule and an increase in the melanomacrophage number were determined. In high-dose group, in addition to increases in the melanomacrophages, separations in capsule, haemorrhage below capsule and within splenic tissue, sinusoidal enlargement, congestion in dilated sinusoid, hypertrophic plasma cells and fibrosis were determined as important histological lesions in exposed frogs. This study clearly showed that carbaryl caused important histopathological damages in splenic tissue of Pelophylax bedriagae. In view of these findings, it can be said that this insecticide has the capacity to disrupt spleen' functions.

Direct and indirect photolysis of the antibiotic enoxacin: kinetics of oxidation by reactive photo-induced species and simulations

Abstract

The purpose of this study was to investigate the aqueous phase photochemical behavior of enoxacin (ENO), an antibiotic selected as a model pollutant of emerging concern. The second-order reaction rate constants of ENO with hydroxyl radicals (HO^●) and singlet oxygen (¹O₂) were determined at pH 3, 7, and 9. Also, the rate constants of the electron transfer reaction between ENO and triplet states of chromophoric dissolved organic matter (³CDOM*) are reported for the first time, based on anthraquinone-2-sulfonate (AQ2S) as CDOM proxy. The sunlight-driven direct and indirect ENO degradation in the presence of dissolved organic matter (DOM) is also discussed. The results show that direct photolysis, which occurs more rapidly at higher pH, along with the reactions with HO^● and ³AQ2S*, is the key pathway involved in ENO degradation. The ENO zwitterions, prevailing at pH 7, show k_ENO, HO^●, k_ENO,1O2, and k_ENO,3AQ2S* of (14.0 ± 0.8) × 10¹⁰, (3.9 ± 0.2) × 10⁶, and (61.5 ± 0.7) × 10⁸ L mol⁻¹ s⁻¹, respectively, whose differences at pH 3, 7, and 9 are due to ENO pH-dependent speciation and reactivity. These k values, along with the experimental ENO photolysis quantum yield, were used in mathematical simulations for predicting ENO persistence in sunlit natural waters. According to the simulations, dissolved organic matter and water depth are expected to have the highest impacts on ENO half-life, varying from a few hours to days in summertime, depending on the concentrations of relevant waterborne species (organic matter, NO₃⁻, NO₂⁻, HCO₃⁻).

Up-scaling of tannin-based coagulants for wastewater treatment: performance in a water treatment plant

Abstract

Tannin extracts from the bark of Acacia mearnsii and wood of Schinopsis balansae, commonly known as Quebracho, were employed. These were modified at laboratory sale via the Mannich aminomethylation with formaldehyde and dimethylamine hydrochloride. Some reaction conditions were varied, namely the formaldehyde dosage and reaction time, while keeping the Mannich solution activation time constant, and their influence on the shear viscosity of the created bio-coagulants was evaluated. The effect of the final pH of the products on their shear viscosity was also analyzed. Up-scaling of the Mannich reaction for tannin from South Africa was performed and the procedure developed at 1-L scale was reproducible in upscaled conditions. One example of a modified South Africa tannin and the modified Quebracho tannin was subsequently selected for the treatment of an industrial wastewater and tested for color and turbidity reduction in jar tests. The effluent treatment was carried out in a single and dual system with cationic synthetic flocculation agents of different charge degree. Good turbidity and decoloration results (93 and 89% reduction, respectively) were obtained with the simultaneous introduction of a cationic, 40% charged polyacrylamide, with minimal dosage (5 ppm) of the latter additive. The tannin-based coagulant from Acacia mearnsii was successfully applied in dual system with cationic polyacrylamide flocculant for industrial wastewater treatment at pilot plant scale. It was shown to satisfactorily treat the water and generate less sludge.

Superb removal capacity of hierarchically porous magnesium oxide for phosphate and methyl orange

Abstract

Here, we successfully developed a template-free way to fabricate hierarchically porous magnesium oxide (MgO) and carefully investigated the adsorption behavior for phosphate and methyl orange (MO). The average pore size and the percentage porosity decreased with the increase in the feeding ratio of Mg²⁺/NH₃. Among the three samples, MgO-25 shows the highest surface area of 63 m² g⁻¹ determined by the mercury intrusion method, and MgO-50 exhibits the highest BET surface area of 121 m² g⁻¹. For all the MgO samples, the adsorption process follows the pseudo second-order and Langmuir isotherm for phosphate, while pseudo second-order and the Freundlich isotherm for MO. Among the investigated samples, MgO-25 shows the most maximum removal capacity of 478.5 mg g⁻¹ for phosphate and the highest removal capacity of 4483.9 mg g⁻¹ for MO. This study compromises a low-cost and convenient dual function material for excellent water remediation of multiple industries.

The contribution of wind wave changes on diminishing ice period in Lake Pyhäjärvi during the last half-century

Abstract

To address the contribution of long-term wind wave changes on diminishing ice period in Northern European lakes, an in situ observation of wind waves was conducted to calibrate a wind-wave numerical model for Lake Pyhäjärvi, which is the largest lake in southwest Finland. Using station-measured hydrometeorological data from 1963 to 2013 and model-simulated wind waves, correlation and regression analyses were conducted to assess the changing trend and main influences on ice period. Ice period in Lake Pyhäjärvi decreased significantly over 51 years (r = 0.47, P < 0.01). The analysis of main hydrometeorological factors to ice period showed that the significant air temperature rise is the main contributor for the diminishing of ice period in the lake. Besides air temperature, wind-induced waves can also weaken lake ice by increasing water mixing and lake ice breakage. The regression indicated that mean significant wave height in December and April was negatively related to ice period (r = − 0.48, P < 0.01). These results imply that long-term changes of wind waves related to climate change should be considered to fully understand the reduction of aquatic ice at high latitudes.

Historical accumulation and ecological risk assessment of heavy metals in sediments of a drinking water lake

Abstract

Heavy metal contamination in sediments is progressively being recognized as a challenging problem in large parts of the developing world, particularly in Asian countries. A drinking water lake in Yunnan-Guizhou plateau, China named Hongfeng Lake was selected as the research target. Forty surface sediment samples and 4 sediment cores were collected to reveal the accumulation of heavy metals in the sediments of the lake. The mean concentrations of Cr, Cu, Pb, Cd, As, and Hg in surface sediments were 81.67, 45.61, 29.78, 0.53, 22.71, and 0.25 mg/kg, respectively, which exceeded the background levels of sediment 1.1~3.3 times. The calculation of geoaccumulation (I_geo) and potential ecological risk (PER) index analysis were preformed, and the results showed a considerable risk for Cd and Hg on the whole. Spatially, the northern part showed a higher risk than the southern part and tributaries of the lake, and a moderate risk in the overall sediment of the lake. The historical level of heavy metals in Hongfeng Lake was traced by vertical sediments study and it was dated back approximately 35 years. The EF trends of a feature sampling site HF8 showed strong temporal variations, and peaked in the year 1995. After that, the EFs exhibited a declining trend, which reflects productive environmental protection and management by the local government. For the Hongfeng Lake, a typical lake with heavy metal-contaminated sediments, the in-situ remediation technique could be a suitable method for its remediation.

Características clínicas, dermatoscópicas e histológicas de varios casos de vasculitis eosinofílica recurrente cutánea

Publication date: Available online 21 June 2018
Source:Actas Dermo-Sifiliográficas
Author(s): E.G. Quijano-Gomero, M.J.M. Rodríguez-Zúñiga, M.E. Sanz-Montero, D. Durand-Buse
La vasculitis eosinofílica recurrente cutánea primaria es una enfermedad rara, caracterizada por placas purpúricas, eritematosas y pruriginosas asociadas a edema. Comparamos y analizamos las características clínicas, dermatoscópicas e histológicas de la enfermedad en 4 pacientes de nuestro hospital y en 13 casos de pacientes publicados previamente. Se incluyeron 17 pacientes, con una mediana de edad de 56 años, y una mediana de duración de la enfermedad de 6 meses. En la mayoría de los casos las lesiones fueron generalizadas (47%) o localizadas en los miembros inferiores (41%). Las características histológicas más frecuentes fueron: color purpúrico (71%), edema local (65%), vasculitis necrosante (94%) e infiltración eosinofílica (100%). La mayoría de los pacientes (82,4%) recibió esteroides orales (mediana de la dosis de 30mg). La vasculitis eosinofílica recurrente cutánea primaria podría ser una entidad clínica infradiagnosticada. El análisis de los pacientes nos permitió proponer algunos criterios diagnósticos para su definición. Recomendamos una estrategia terapéutica con esteroides de alta potencia y dapsona, pudiéndose considerar como el tratamiento de primera línea.Primary recurrent cutaneous eosinophilic vasculitis is a rare condition characterized by pruritic, erythematous, purpuric plaques associated to edema. We compared and analyze the clinical, dermoscopic and histological features of the disease in 4 patients from our hospital and 13 patients published in the literature. Seventeen patients were included, with a median age of 56yo, a median duration of disease of 6 months. Lesions were most frequently generalized (47%) or localized in lower limbs (41%). The most frequent features were purpuric color (71%), local edema (65%), necrotizing vasculitis (94%) and eosinophil infiltration (100%) in histology. Most of the patients (82.4%) were given oral steroids with a median dose of 30mg. Primary recurrent cutaneous eosinophilic vasculitis might be an infra-diagnosed condition. The analysis of the patients allowed us to propose diagnostic criteria for the definition of this disease. We suggest a therapeutic strategy with high-potency steroids and dapsone, which might be considered as first-line treatment.

Graphical abstract

Pénfigo vegetante en pliegues inguinales

Publication date: Available online 21 June 2018
Source:Actas Dermo-Sifiliográficas
Author(s): R. Rodriguez-Lojo, M.M. Otero-Rivas, T. Usero Bárcena, I. Castiñeiras Mato

Tacrolimus ointment for the treatment of adult and pediatric atopic dermatitis: Review on safety and benefits

The Journal of Dermatology, EarlyView.

Incidence of hydrological, chemical, and physical constraints on bacterial pathogens, Nocardia cells, and fecal indicator bacteria trapped in an urban stormwater detention basin in Chassieu, France

Abstract

The nature and fate of urban contaminants washed by stormwater events and accumulating in a detention basin (DB) were investigated. Relations between bacterial and chemical contaminants of trapped urban sediments, and field parameters were analyzed. Fecal indicators and some pathogens known to be environmentally transmitted (Nocardia, Pseudomonas aeruginosa, and Aeromonas caviae) were tracked, and their persistence investigated. Six sampling campaigns were carried out over 3 years, using five sites including a settling chamber (SC). Aerosolized bacteria at these sites were also monitored. Deposits in the basin were made of fine particles and their content in chemical pollutants was found highly variable. High polycyclic aromatic hydrocarbon (PAH) contents were measured but only three pesticides, over 22, were detected. Deposits were significantly contaminated by fecal indicator bacteria (FIB), P. aeruginosa, A. caviae, and by Nocardia. Only A. caviae showed significant numbers in aerosolized particles recovered over the detention basin. Nocardia spp. cells heavily contaminated the SC. The efficacy of the detention basin at reducing bacterial counts per rain event and over time were estimated. A slight drop in the counts was monitored for fecal indicators but not for the other bacterial groups. Hydrodynamic parameters had a strong impact on the distribution and features of the deposits. Multiple factors impacted the fate of FIB, P. aeruginosa, A. caviae, and Nocardia cells, but in a group dependent manner. Nocardia counts were found positively correlated with volatile organic matter. FIB appeared highly efficient colonizers of the DB.

Photochemical response of parsley (Petroselinum crispum (Mill.) Fuss) grown under red light: The effect on the essential oil composition and yield

Publication date: Available online 21 June 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Roberta Ascrizzi, Daniele Fraternale, Guido Flamini
The effect of different wavelengths on plants morphological characters has been widely described, but also the chemical composition of the essential oil is influenced by the lighting conditions in which they are grown. In the present study, the effect of both the enrichment (reverse Emerson effect) and the monochromatic lighting treatments with red light has been evaluated on the essential oil compositions of parsley (Petroselinum crispum (Mill.) Fuss). Multivariate statistical analysis was performed on the results, with both the hierarchical cluster and principal component analyses. Whilst the red-enrichment of the light spectrum did not induce major changes in the essential oil composition, the end of the day monochromatic red (660 nm) treatment caused a chemotype switch in the essential oil and relevant differences in the overall composition, with an increment of the relative abundance of oxygenated compounds, coupled with a relevant decrement in the abundance of phenylpropanoids. The extraction yields remained unchanged in all the three tested conditions of light (control, red-enriched and monochromatic red). Different lighting conditions could be used as a tool to modulate the compounds present in the essential oil, but further studies would be advisable to assess the effects on different species and chemical classes of compounds.

Supramolecular self-assembly of bacteriochlorophyll c molecules in aerosolized droplets to synthesize biomimetic chlorosomes

Publication date: August 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 185
Author(s): Vivek B. Shah, Chloe Ferris, Gregory S. Orf, Shalinee Kavadiya, Jessica R. Ray, Young-Shin Jun, Byeongdu Lee, Robert E. Blankenship, Pratim Biswas
The unique properties of chlorosomes, arising out of the self-assembled bateriochlorophyll (BChl) c structure, have made them attractive for use in solar cells. In this work, we have demonstrated the self-assembly of BChl c in aerosolized droplets to mimic naturally occurring chlorosomes. We compare two different methods for self-assembly of BChl c, one using a single-solvent and the other using two-solvents, and demonstrate the superiority of the two-solvent method. Results show that the self-assembled BChl c sprayed at different concentrations resulted in a varying red shift of 69–75 nm in absorption spectrum compared to the solution, which has peak at 668 nm corresponding to the monomeric BChl c. The sample fluoresces at 780 nm indicating a quality of self-assembly comparable to that observed in naturally occurring chlorosomes. In order to mimic chlorosomes, solution containing BChl c, BChl a, lipids and carotenes in same proportion as in chlorosomes is sprayed. The resulting self-assembly has an absorption peak at 750 nm, shifted by 82 nm compared to that of monomers and the fluorescence peak at 790 nm. Thus in presence of lipids and carotenes, both the absorption and fluorescence peaks are red shifted. Further, using grazing incidence small angle X-ray scattering (GISAXS), we characterized the deposited films, and the 2D X-ray scattering patterns of sample clearly indicate the distinct lamellar structure as present in chlorosomes. The results of this work provide new insights into self-assembly in aerosolized droplets, which can be used for assembling a wide range of molecules.

Autologous Costal Cartilage Harvesting Technique and Donor-Site Pain in Patients Undergoing Rhinoplasty

To the Editor We read with great interest the article by Özücer et al. The authors did well to compare the postoperative donor-site pain in patients who underwent costal cartilage harvest, and the separated evaluation of resting pain and movement pain is thoughtful and exquisitely considered and worthy of praise. In this communication, we would like to propose some discussions with the authors.

Autologous Costal Cartilage Harvesting and Donor-Site Pain in Patients Undergoing Rhinoplasty—Reply

In Reply We read the letter by Lu and Fan regarding our recently published article. We are happy with the authors' interest, praise, and the discussions they've contributed. Although the technique has been widely used and reported by many influential authors, we agree with the opinion of Lu and Fan that monopolar electrocautery (ME) causes tissue damage and prolongs wound healing. Nevertheless, we don't think it is an interference factor for this study because the major aim of what we are investigating is the downside of ME in that aspect.

Use of Objective Metrics in Dynamic Facial Reanimation

This systematic review examines whether objective instruments of midface movement are reported to be used in outcome measurements for patients treated with dynamic methods for facial paralysis.

Surgical re‐excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes

British Journal of Dermatology, EarlyView.

DIPG-23. BRAINSTEM RADIATION EXPOSURE CONFERS SUBSTANTIAL RISK OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN MEDULLOBLASTOMA SURVIVORS: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY

Abstract

With improved survivorship in medulloblastoma, there has been increasing recognition of the occurrence of secondary malignant brain tumors. To date, no studies have specifically addressed the risk of diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. We queried the International DIPG Registry and identified six cases of DIPG with prior medulloblastoma. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials. Incidence of DIPG after medulloblastoma ranged from 0.3–3.9%. All 12 cases underwent surgical resection followed by craniospinal photon irradiation (range 18–36 Gy) and posterior fossa boost (range 19.8–36 Gy). Posterior fossa exposure was greater than 53 Gy in all cases. Median time to diagnosis of secondary DIPG was 7 years (range 2–11 years). Patients died of secondary DIPG a median of 8 months after diagnosis (range 4–17 months). Molecular subgroup of primary medulloblastomas with available tissue (n=5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). Tumor/germline exome sequencing of three secondary DIPGs demonstrated tumors to be H3.3 wildtype and harbor higher mutational burden than radiation-naïve DIPGs. Mutational signature analysis of secondary DIPGs showed mutations consistent with radiation-induced DNA damage (e.g., insertional event in TP53), as well as mutations in other oncogenic drivers (e.g., NRAS, PI3KCA), suggestive of distinct mutational processes compared with primary DIPGs. In conclusion, we report for the first time that survivors of pediatric medulloblastoma are at risk for the development of secondary DIPG, likely consequent to radiation exposure. This risk highlights the importance of radiation field, volume, and modality in medulloblastoma treatment.

IMMU-09. OUTCOME OF PATIENTS WITH RECURRENT DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TREATED WITH PEMBROLIZUMAB (ANTI-PD-1): A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)

Abstract

INTRODUCTION

Children with diffuse intrinsic pontine glioma (DIPG) have a dismal prognosis. Checkpoint blockade has revolutionized treatment of some resistant cancers.

METHODS

Pembrolizumab, a PD-1 inhibitor, was administered to children with progressive DIPG (Stratum A) and results are reported here. Children aged 1-18yrs with progressive DIPG were eligible with functional scores >60 and physiologic or less steroid usage, among standard eligibility criteria. Pembrolizumab was administered at 2mg/kg IV every three weeks. Tumor tissue (if available), serum and MRI studies were collected for correlative analysis.

RESULTS

Five patients with progressive DIPG were enrolled from June-July 2015. The median age at diagnosis was 3.5yrs (range,2.8-6.9), and median time from diagnosis to study entry was 14.6 months (range,8.7-20.7). Progression-free survival (PFS) was 1.02 months (range,0.5-1.7); overall survival from initial treatment was 1.7 months (range,0.5-6.2). All patients clinically and/or radiographically worsened after one (n=1) or two (n=4) doses of pembrolizumab. Grade 3 or greater treatment-related adverse events included fatigue (n=2) and new or increased grade neurologic symptoms. Correlative analysis is ongoing.

CONCLUSIONS

Checkpoint inhibition holds potential for CNS cancer treatment; however, special consideration is required in the CNS with limited space and large disease burdens. In our study, patients rapidly deteriorated neurologically after initiation of checkpoint blockade, with a shorter median PFS than expected by analogous historical trials; pembrolizumab protocols were amended to exclude recurrent DIPG patients after these events. Our findings suggest caution when utilizing immunotherapy in actively progressing tumor in the brain stem.

TBIO-19. MASS SPECTROMETRY OF COMMON CEREBELLAR TUMOURS IDENTIFIES DIFFERENCES IN METABOLISM

Abstract

Metabolic profiling by Magnetic Resonance Spectroscopy has shown the three most common paediatric cerebellar tumours are metabolically distinct; however, these techniques are limited by their sensitivity. Mass spectrometry is more sensitive and able to detect many more metabolites. In this study, metabolic phenotyping was performed to investigate the water-soluble metabolome and the lipidome of the three most common paediatric cerebellar tumours with the aim of informing a detailed metabolic pathway analysis. A discovery based experiment was performed on 60 surgically resected snap frozen pilocytic astrocytomas, ependymomas and medulloblastomas using UPLC-MS assays to detect water soluble and lipid metabolites. Principal component analysis demonstrates separation of the tumours based on the relative concentration of thousands of detected metabolites. The relative concentrations of glucose and glycolytic intermediates varied between the tumour types, as did metabolites involved in purine and pyrimidine metabolism. Key metabolites within the taurine metabolism pathway were found to be higher in medulloblastoma. Alterations were observed in lipid metabolism, with a wide range of relative concentration differences in di- and triacylglycerides, sphingolipids, ceramides, cardiolipins and glycerophospholipids. This study has shown that these tumours are metabolically distinct and offer the opportunities for stratified diagnosis and treatment. Some of the observed changes in relative concentration between the tumours reflect findings from spectroscopic studies, particularly with regards to taurine which is known to be higher in medulloblastoma. The ability of mass spectrometry to identify and measure lipid species and low concentration metabolites from tissue could allow targetable metabolic differences to be characterised and exploited.

IMMU-10. NIVOLUMAB IN THE TREATMENT OF RECURRENT OR REFRACTORY PEDIATRIC BRAIN TUMORS: A SINGLE INSTITUTIONAL EXPERIENCE

Abstract

Tumor cells evade immune-mediated destruction through activation of checkpoints. Successful use of the immune checkpoint inhibitors in certain cancer types has generated interest in using this approach in pediatric brain tumors. Ten consecutive children (6 boys, 4 girls, mean age 11 years, range 2-17 years) with pediatric recurrent or refractory pediatric brain tumors (4 high grade glioma, 2 pineoblastoma, 1 disseminated low grade glioma, 1 medulloblastoma, 1 ependymoma, 1 primitive neuro-ectodermal tumor) were treated at Rady Children's Hospital San Diego from 2015-2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 weeks). Eight had received prior chemotherapy and 9 received prior radiation therapy. Seven had radiographic progression of disease (total 36 doses, mean 3.6 doses) with mean time to progression of 5.4 weeks (range 1.6-13.7 weeks). One patient voluntarily discontinued treatment after stable disease at 24 weeks and 2 patients showed either transient stability or partial response of brain disease but worsening of metastatic disease. There were no dose limiting side effect observed, however there was a 10 % incidence of elevated ALT, hyperglycemia, pancreatitis and hypo-albuminemia. Although the tumor mutation burden (TMB) was low (mean 2, range 0-6.3), there was a trend between TMB and time to progression. PDL-1 immuno-histochemical analysis and next generation sequencing data on each tumor will be presented. Our findings suggest nivolumab is well tolerated in pediatric patients with recurrent brain tumors. Future randomized controlled studies stratifying for TMB may be necessary to demonstrate the efficacy of PD-L1 inhibitors in recurrent pediatric brain tumors.

EPID-11. SYSTEMATIC REVIEW ON TREATMENT-RELATED HAEMATOLOGICAL ADVERSE EVENTS AFTER TEMOZOLOMIDE FOR A CNS TUMOUR

Abstract

BACKGROUND

Temozolomide is a widely used alkylating cytostatic drug for CNS tumours. Severe treatment-related haematological adverse events (tHAE) after the application of temozolomide are reported whilst the true incidence is elusive. The aim of this study is to determine the incidence, the risk-factors for, and course of secondary haematological adverse events after treatment with temozolomide in patients with CNS tumours.

METHODS

We reviewed the English literature between 1995-2016 on cases describing treatment-related haematological adverse events after temozolomide and set up a country-wide survey among (paediatric) neuro-oncologists in the Netherlands.

RESULTS

In 20 out of 199 manuscripts deriving from the literature search 26 cases (age 0-69, median 40,5 years) were found with a severe tHAE event after temozolomide: 5 aplastic anemia, 5 acute lymphoblastic leukemia, 9 acute myeloblastic leukemia, 1 diffuse large B-cell lymphoma, 6 myelodysplastic syndrome and 1 mixed lineage leukemia. Karyotype was detected in 17/26 cases, mainly monosomy 5&7. Quality check of the literature mainly showed missing data on predisposing family history. Seven additional cases of a t-HAE after TMZ in CNS a tumour were discovered via a clinical survey in the Netherlands. The median latency in developing a t-HAE was 14 months, the survival after t-HAE was median 4,5 months.

CONCLUSIONS

tHAE is rare and develops relatively early after treatment with temozolomide, while insufficient insight could be found for risk-factors for a t-HAE after temozolomide. Although most patients die from their secondary tHAE, its course differs substantially between individual cases.

IMMU-11. BRAINCHILD PIPELINE: LOCOREGIONAL IMMUNOTHERAPY WITH CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELLS FOR RECURRENT/REFRACTORY CENTRAL NERVOUS SYSTEM TUMORS

Abstract

Chimeric antigen receptor (CAR) T-cell therapy carries the promise of a broadly applicable, targeted, yet molecular pathway-independent, intervention for pediatric central nervous system (CNS) tumors. The BrainChild pipeline at Seattle Children's utilizes engineered CAR T-cells directed against the surface epitopes HER2, EGFR, B7-H3 and IL13Ralpha2, which are commonly expressed in pediatric CNS tumors including high-grade glioma, diffuse intrinsic pontine glioma, medulloblastoma, and ependymoma. Using in vitro and in vivo preclinical modeling, we have optimized the efficacy and specificity of the CAR constructs. The extracellular target-specific scFv domain for the HER2-specific and EGFR-specific CARs are derived from trastuzumab and an EGFR806 antibody, respectively. Third-generation CAR T-cells with medium-length (HER2-CAR) and short (EGFR806-CAR) spacers coupled to an intracellular 4-1BBζ domain result in complete and durable tumor eradication in mouse xenograft CNS tumor models. We now are poised to begin enrolling Phase 1 clinical trials for children and young adults with recurrent or refractory CNS tumors expressing the respective target epitopes. We will deliver locoregional adoptive therapy with autologous CD4 and CD8 T cells lentivirally transduced with the optimized CAR constructs. Using a dose-escalation regimen, CAR T-cells will be injected on a weekly schedule via indwelling catheters into the tumor resection cavity or the ventricular system. The primary objectives are safety and feasibility, along with secondary and exploratory objectives to define the CAR T-cell distribution in the CSF and peripheral circulation, target epitope expression across tumor populations, progression free and overall survival, and biomarkers of anti-tumor CAR T-cell activity.

CRAN-16. IMPORTANCE OF SURGICAL INTERVENTION IN RECOVERY OF VISUAL FUNCTION IN A TEENAGER WITH AN ACIDOPHILIC STEM CELL ADENOMA

Abstract

BACKGROUND

Prolactin-secreting macroadenomas are generally not life-threatening and often present with visual impairment. Medical management with a dopamine agonist is typically the treatment of choice, which significantly reduces the tumor size and improves symptoms without surgical morbidity. In this report, we present a case of an acidophilic stem cell adenoma (ASCA) that was slowly responsive to medical management, but exhibited marked visual recovery after surgical resection.

RESULTS

A 15 year-old previously healthy male presented with significantly decreased peripheral vision but no other neurologic or endocrinologic symptoms. Initial magnetic resonance imaging of the brain/spine revealed a mass in the suprasellar and sellar regions with extension into the cavernous sinus and a prolactin level of 644, leading to a presumptive diagnosis of macroprolactinoma. Medical management with cabergoline resulted in some decrease of the prolactin level, but no radiographic improvement or visual recovery after two months. He subsequently underwent endoscopic endonasal transsphenoidal resection with near-total restoration of his peripheral vision post-operatively and significant improvement of his prolactin level. Pathology was consistent with an ASCA (staining positively with prolactin, growth hormone (a-subunit), and pituitary-specific positive transcription factor 1), a rare pituitary adenoma that tends to be invasive and often requires more aggressive therapy; the patient thus underwent focal consolidative proton beam irradiation.

CONCLUSION

This case highlights the importance of considering acidophilic stem cell adenomas in the differential of medically-resistant pituitary macroadenomas and early consideration of resection in cases where significant visual or other symptoms exist, as timely intervention may substantially improve functional outcomes.

IMMU-12. T-CELL THERAPIES DEMONSTRATE EFFICACY WITHOUT TOXICITY IN IMMUNOCOMPETENT MODELS OF BRAINSTEM TUMORS

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a pediatric brainstem tumor with a dismal prognosis and no curative treatments. Immunotherapy has been considered as a treatment for these tumors because of its ability to provide specific and sustained tumor killing. By nature, this approach is inflammatory and remains controversial due to the potential for catastrophic inflammatory toxicity in the brainstem. In order to address whether this approach should be considered as a clinical option, we characterized the efficacy/toxicity profile of transgenic and chimeric antigen receptor (CAR) T-cell therapies in the brainstem using immunocompetent, syngeneic mouse models. We first adoptively transferred naïve transgenic T-cells recognizing the model tumor antigens gp100 or ovalbumin to treat established aggressive, transplantable murine tumors in the brainstem. Encouragingly, this therapy significantly extended median survival (16 to 32 days; p<.001) with no signs of therapeutic toxicity. We plan to expand these studies by incorporating hgp100 into a spontaneously-occurring, engineered model of DIPG, followed by transgenic T-cell treatment. Lastly and most clinically-relevant, we have used CAR T-cell therapy to treat B16 melanoma engineered to express EGFRvIII and implanted into the brainstem. This therapy extended median survival from 14 to 30 days (p<.001). We plan to evaluate whether combinatorial approaches using checkpoint inhibitors or oncolytic viruses can further enhance survival. Together these data from immunocompetent mouse models demonstrate that T-cell immunotherapies are well- tolerated and efficacious against tumors located in the brainstem, opening the door for future clinical trials.

EAPH-11. INTRAVENTRICULAR THERAPY ALTERNATING ETOPOSIDE, AQUEOUS CYTARABINE AND TOPOTECAN IS FEASIBLE AND SAFE: EXPERIENCE IN 26 PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS

Abstract

BACKGROUND

Malignant brain tumors carry a high risk for leptomeningeal dissemination, but tumor cells floating in the CSF are often not affected by systemic and/or antiangiogenic chemotherapy. Since liposomal cytarabine was removed from the market, alternatives for intraventricular therapy are desperately needed. We report on our experience with an intraventricular therapy consisting of alternating cycles of etoposide, aqueous cytarabine and topotecan. PATIENTS AND

METHODS

Between 2008 and 2017, 26 patients aged 1 to 17 years (median 7 years) with various malignant brain tumors received intraventricular therapy via an Ommaya reservoir, consisting of alternating etoposide 0.5mg on five consecutive days (<1 year 0.25mg), topotecan 0.4mg twice a week (>1 and <2 years 0.25mg, >2 and <3 years 0.32mg) and aqueous cytarabin 30mg twice a week (<1 year 16mg, >1 and <2 years 20mg, >2 and <3 years 26mg).

RESULTS

1899 doses of etoposide (4–166/patient), corresponding to 2–36 five-day-cycles/patient (median 17), alternating with 307 doses of topotecan (1–49/patient, median 10), and 101 doses of aqueous cytarabine (1–28/patient, median 4) were administered. Treatment was given over a period of 1 – 115 months (median 12 months). Alternating intraventricular treatment was generally well tolerated. One boy with multiple recurrences of an ependymoma in the posterior fossa showed increased tremor after topotecan, another girl reported fatigue after topotecan.

CONCLUSION

Alternating intraventricular therapy with etoposide, aqueous cytarabine and topotecan is feasible and generally well tolerated, and can be an important addition for patients with malignant brain tumors.

IMMU-13. A FAILURE TO RESOLVE INFLAMMATION: ROLE OF RESOLVINS IN THE TREATMENT OF PEDIATRIC CNS TUMORS

Abstract

BACKGROUND

Current brain tumor therapies are focused on reducing tumor burden by inducing apoptotic and necrotic tumor cells. However, inflammation in the tumor microenvironment caused by this debris can accelerate tumor progression. Inflammation is endogenously regulated resolvins and protectins, molecules that are biosynthesized and act in the brain and cerebrospinal fluid. They clear cellular debris via local macrophages while reducing localized inflammatory cytokines. We hypothesized that control of inflammation through resolvins and protectins could represent a novel treatment modality by pharmacologically promoting the clearance of tumor cell debris by microglia, thereby depriving the surviving tumor cells of inflammatory stimuli. METHODS AND

RESULTS

We show that debris generated by killing of either medulloblastoma or glial tumors (using cisplatin chemotherapy, dabrafenib targeted therapy or the epigenetic inhibitors JQ1) stimulate residual live tumor cells to grow. This effect was inhibited by nanogram levels of resolvins/protectins and without toxicity in a variety of tumor types including orthotopic models. The effect was mediated via enhanced macrophage and microglial phagocytosis of tumor cell debris and counter-regulation the secretion of pro-inflammatory cytokines/chemokines, including CCL5, TNFα, CCL2, CXCL1, and CCL4.

CONCLUSIONS

We show that resolvins and protectins stimulate the clearance of tumor cell debris by stimulating macrophage and microglial phagocytosis and counter-regulating pro-inflammatory and pro-tumorigenic cytokines. This approach not only has relevance to our current approaches to cancer therapy (focused on maximal tumor cell kill), but may have an impact on the side effects of current immunotherapies where therapy induced inflammation in the tumor results in significant morbidity.

HGG-36. NFκB AND FOXM1 MEDIATE ANTI-CANCER ACTIVITY OF DUAL HDAC AND PI3K INHIBITION IN PEDIATRIC HIGH GRADE GLIOMA AND DIPG

Abstract

Pediatric high-grade gliomas (pHGGs) and diffuse intrinsic pontine gliomas (DIPGs), portend a poor prognosis and are particularly recalcitrant to standard treatment. Aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway have been identified as important mediators of pHGG and DIPG pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of DIPG patients, we sought to explore radiosensitizing functions of such inhibition and explore mechanisms of action of such agents. Here, we demonstrate that treatment with CUDC-907, a novel, first-in-class dual inhibitor of histone deacetylases (HDACs) and PI3K, in combination with radiotherapy evokes a synergistic cytotoxic response in pHGG and DIPG models in vitro and in vivo. We identify a novel mechanism of CUDC-907 in modulating DNA damage response by inhibiting radiation-induced DNA repair pathways, including homologous recombination and non-homologous end joining. The radiosensitizing effects of CUDC-907 were mediated by decreasing NFκB/Forkhead box M1 (FOXM1) recruitment to promoters of genes involved in the DNA damage response, and exogenous expression of NFκB/FOXM1 rescued CUDC-907-induced cytotoxicity. Together, these findings reveal CUDC-907 as a novel radiosensitizer with potent anti-tumor activity in pHGG and DIPG, and provide a preclinical rationale for the combination of CUDC-907 with radiotherapy as a novel therapeutic strategy for pHGG and DIPG. More globally, we have identified NFκB and FOXM1, and their downstream transcriptional elements, as critical targets for new treatments for pHGG and DIPG.

IMMU-14. KICKSTARTING THE CANCER IMMUNITY CYCLE BY INNATE CHECKPOINT INHIBITION TO TARGET PEDIATRIC BRAIN TUMORS

Abstract

Recently we published the effect of a humanized anti-CD47 antibody, on five aggressive and etiologically distinct pediatric brain tumors: Group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrates therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Disabling the inhibitory signals transduced by SIRPa by blocking anti- CD47 antibodies we promote phagocytic response driven by tumor-specific antibodies. These phagocytic innate cells are also professional antigen-presenting cells (APC), providing a link from innate to adaptive antitumor immunity. Consequently, we tested a number of approaches to augment immune checkpoint immunotherapy. We hypothesized that by activating immunogenic phagocytosis we could kickstart the cancer immunity cycle and hence augment adaptive checkpoint inhibitors against cold tumors such as medulloblastoma and pediatric glioma.

RESULTS

To determine the in vivo efficacy of combinatorial anti-CD47 and anti-PD1 therapies, spontaneous SHH medulloblastoma mouse models were treated by, i.p. injections with either PBS (control), anti-CD47, anti-PD1 or in combination. To test the cancer immunity hypothesis combination treatment was carried out either in sequence or simultaneously. Mice receiving anti-CD47 anti-PD1 duotherapy demonstrated increased survival when treated sequentially as compared to both monotherapies and control cohorts. Immunohistochemical and Flowcytometry analysis with the macrophage marker F4/80 and T-cell subset immune panel demonstrated varying patterns of macrophage and T-cell infiltration. Addition of anti-CTLA4 mAb did not enhance the efficacy of this effect suggesting the lack of infiltrating T-regulatory cells.

ATRT-22. SWI/SNF COMPLEX HETEROGENEITY RELATES WITH POLYPHENOTYPIC DIFFERENTIATION AND THE IMMUNE MICRO ENVIRONMENT IN RHABDOID TUMORS

Abstract

Malignant rhabdoid tumors (MRT), including central nervous system (CNS) Atypical Teratoid / Rhabdoid Tumors (AT/RT) and extra CNS (eCNS) MRT, are aggressive cancers characterized by loss of SMARCB1, a core component of the SWI/SNF chromatin-remodeling complex. Histopathologically, MRTs are characterized by polyphenotypic differentiation that varies from tumor to tumor. Because the SWI/SNF complex regulates differentiation we hypothesized that the SWI/SNF complex would exhibit heterogeneity in MRTs. We first characterized the SWI/SNF complex in developing human brain. SMARCB1 expression was highest in the cerebellum compared to hemispheric regions and remained so throughout development. In contrast, many subunits of the SWI/SNF complex were down regulated after cerebellar development. In MRTs we discovered that the SWI/SNF complex subunits showed marked differences between AT/RTs and eCNS MRTs. In eCNS MRTs high ACTL6A and ACTL6B expression was associated with neuronal differentiation while tumors with low ACTL6A and ACTL6B showed epithelial and mesenchymal differentiation. In AT/RTs there was marked heterogeneity in members of the PBAF complex including ARID2, BRD7 and PBRM1. Tumors with high PBAF expression were associated with worse prognosis, increased metastasis and cell cycle deregulation. Of the PBAF components, tumors with low PBRM1 showed a better prognosis and were associated with increased cytotoxic lymphocytes in their microenvironment. Our data demonstrate that MRTs exhibit heterogeneity in the SWI/SNF complex that may contribute to the polyphenotypic differentiation characteristic of these tumors, and which may have implications in understanding the biology, prognosis and development of immunotherapeutic approaches to these tumors.

IMMU-15. HIGH-RESOLUTION ANALYSIS OF THE T-CELL RECEPTOR REPERTOIRE AFTER ADOPTIVE CELLULAR THERAPY IN PEDIATRIC PATIENTS WITH CENTRAL PNETs (Re-MATCH TRIAL)

Abstract

Adoptive cellular therapy (ACT) using transfer of tumor-specific lymphocytes has emerged as a potent strategy for treatment of advanced and refractory malignancies. We have employed deep TCR repertoire sequencing approach to explore dynamics of T-cell immunity in the nine patients with recurrent medulloblastoma and PNETs undergoing adoptive cellular therapy (Re-MATCH protocol, FDA IND BB-14058). Total RNA was isolated from patient PBMC samples collected prior to adoptive cellular therapy and weekly for one month and then monthly following immunotherapy treatment. cDNA was generated with addition of a common adapter at 5' end of cDNA using RACE technology. Raw sequencing data were preprocessed using MiXCR software. Further TCR repertoire analysis was performed using tcR R-package and VDJtools software. We observed remarkable dynamic changes in the TCR repertoire in peripheral blood following ACT in all patients. The blood samples collected after adoptive cellular therapy revealed that certain T-cells were clonally expanded after ACT, with an increasing number of "hyper-expanded" TCR clones (comprising >1% of all TCR beta or alpha sequences). Hyper-expanded TCR clones and increased TCR diversity following ACT was associated with radiographic response to ACT and prolonged progression-free and overall survival. Limited TCR expansion and diversity following ACT was observed in patients with short overall and progression-free survival. These findings support further study of the use of TCR sequencing to monitor responses to adoptive cellular therapy and suggest that TCR clonal expansion and increasing TCR diversity following treatment may be associated with positive clinical responses.

DEV-09. ST. JUDE GLOBAL ACADEMY NEURO-ONCOLOGY SEMINAR: THE CREATION OF A TARGETED CURRICULUM FOR GLOBAL NEURO-ONCOLOGY

Abstract

The majority of the burden of pediatric patients with central nervous system (CNS) tumors resides in low- and middle-income countries (LMICs). The success of the treatment of this patient population relies on an effective multidisciplinary team, with updated knowledge and skills and, most importantly, awareness of the context in which they practice. The SJGANOS seeks to change the paradigm of educational interventions in pediatric oncology, by systematically creating a curriculum with directed educational interventions that will lead to improved patient outcomes. A targeted needs assessment (TNA) survey to evaluate the care team members, team dynamic, infrastructure, and patient outcomes was designed and distributed to 20 centers around the world. This TNA will describe the current state of neuro-oncology as a field in LMICs and define high-impact educational interventions. Since interdisciplinary competencies are best gained as a group, teams that treat patients with CNS tumors, including oncologists, neurosurgeons, pathologists, radio-oncologists, and radiologists from around the world will be invited to the SGNOS to be held in the summer of 2018. The Seminar will have two components, a distance-learning course and an onsite workshop, with the goal to provide higher-cognitive skills and provide the basis for a change in behavior. Ultimately, we wish to increase knowledge and skills, increase the multidisciplinary approach to care, and measurably increase the survival and quality of life of patients with CNS tumors around the world.

IMMU-16. CHARACTERIZING TUMOR-IMMUNE INTERACTIONS IN DIFFUSE INTRINSIC PONTINE GLIOMA

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is a universally fatal brain tumor diagnosed in approximately 300 children in the US each year. Radiation modestly extends patient survival and provides temporary relief from symptoms, however, surgical resection is impossible due to the tumor's location in the brainstem, and no chemotherapeutics have shown any efficacy; death generally occurs less than a year after diagnosis. Due to its ability to specifically eliminate tumor cells while leaving healthy tissue intact, immunotherapy could be a major breakthrough in the treatment of DIPG. As a first step towards the rational development of DIPG-specific cellular immunotherapy, we have characterized the immune microenvironment of DIPG tumors using IHC analysis of TMAs and Nanostring transcript analysis of frozen tumor samples. In contrast to pediatric and adult high-grade cortical gliomas (HGGs), DIPGs exhibit minimal infiltration with CD163+ myeloid cells or CD8+ T cells, consistent with their low mutational burden. Furthermore, unlike adult HGGs in particular, DIPG tumors had low levels of classical immunosuppressive factors including PD-L1, TGFβ, and IL-10. To directly examine the effects of DIPG cells on immune cells, we co-cultured primary tumor cells with immune cells from healthy donors. DIPG tumor cells did not polarize macrophages towards a pro-tumor phenotype, while U87 adult GBM cells did. Furthermore, DIPG cells did not slow T cell proliferation or prevent IFNγ production, while U87 cells did. Together, this suggests that although DIPG tumors are not inducing an immune response, adoptively transferred anti-tumor immune cells will not need to overcome an immunosuppressive microenvironment.

DIPG-55. TARGETING SENESCENT CELLS WITH ABT-263 ENHANCES CELL DEATH INDUCED BY BMI1 INHIBITION AND IONIZING RADIATION IN DIPG

Abstract

Ionizing Radiation (IR) is a key treatment modality for DIPG, but it provides only temporary relief as the tumor cells develop resistance to radiation. Recently, we and others have shown that inhibition of BMI1 either alone or in combination with radiation attenuates DIPG cell proliferation in vitro. While we are demonstrating the in vivo efficacy of pharmacological inhibition of BMI1 and understanding the mechanism of anti-tumor effect of BMI1 inhibition in DIPG, the existence of treatment-resistant cells remains a major obstacle for a prolonged cure. Both IR and genetic or pharmacological inhibition of BMI1 induces cellular senescence as a mechanism to suppress tumor cell proliferation, implying that senescence can be considered as tumor suppressor. Paradoxically, recent studies have shown that accelerated senescence can mediate tumor recurrence due to the development of pro-oncogenic environment. In line with this, we are investigating whether clearance of treatment-induced senescent cells enhances treatment outcomes. DIPG cells exposed to different doses of radiation followed by treatment with ABT-263 (Navitoclax), a drug which selectively clears the senescent cells, resulted in increased radiosensitization. Treatment of pre-radiated DIPG cells with ABT-263 decreased the activity of senescence-associated beta-galactosidase and anti-apoptotic protein expression. Similarly, chemical inhibition of BMI1 in combination with ABT-263 showed synergistic killing of DIPG cells. The synergy was most pronounced in DIPG cells harboring wildtype p53. Our study highlights the importance of eliminating treatment-induced senescent cells while inhibiting proliferation of DIPG tumors, a combination which can immensely improve therapeutic efficacy in DIPG patients.

IMMU-17. HEMATOPOIETIC STEM CELL-DERIVED DENDRITIC CELLS REPROGRAM THE BRAIN TUMOR MICROENVIRONMENT

Abstract

INTRODUCTION

Despite multimodality treatment, patients with malignant gliomas only achieve a median survival of 18 months. Our group has pioneered an adoptive T cell immunotherapy that utilizes total tumor RNA-pulsed dendritic cells to expand polyclonal tumor-reactive T cells ex-vivo. The strongest anti-tumor efficacy of adoptive T cell immunotherapy is achieved when combined with syngeneic hematopoietic stem and progenitor cell (HSPC) transplant. The inclusion of HSPCs leads to a doubling of median survival and 40% long-term cures in treatment-resistant murine malignant glioma, brainstem glioma, and medulloblastoma. In this study, we evaluated the HYPOTHESIS that adoptive T cell immunotherapy drives the differentiation of HSPCs into dendritic cells within the brain tumor microenvironment.

METHODS

We evaluated HSPC differentiation and function in the context of immunotherapy in tumor-bearing animals and HSPC proliferation and differentiation in-vitro using a T cell co-culture system.

RESULTS

The differentiation of HSPCs into CD11c⁺MHCII⁺CD86⁺ dendritic cells in the tumor microenvironment depended on tumor-reactive T cell-released IFN-γ. Additionally, HPSC-derived dendritic cells cross-presented tumor-derived antigens to tumor-reactive T cells, increasing T cell activation within the tumor. When evaluating the impact of HSPCs on host intratumoral immunity, we determined that HSPC transfer strongly supplants host myeloid-derived suppressor cells and downregulates suppressive genes.

CONCLUSIONS

We have made novel observations that HSPCs significantly enhance immunotherapy by supplanting host immunity and synergizing with T cells in the tumor microenvironment. A phase I trial evaluating the impact of HSPC transfer on adoptive immunotherapy in pediatric high-grade gliomas is on schedule to open this year (ACTION– FDA IND#BB-17298).

EPEN-11. ANALYSIS OF EXPRESSION OF YAP1, RELA, MAMLD1 AND FAM118B GENES IN PEDIATRIC EPENDYMOMA

Abstract

Ependymomas (EPN) are primary tumors in the central nervous system (CNS). In children, 90% of EPNs occur intracranial, with two-thirds being located in the posterior fossa (PF) and one-third within the supratentorial (ST) compartment. Despite the development of new molecular classifications and increasing understanding of the underlying EPN mechanisms, management and treatment remain challenging. We investigated the expression of genes involved in EPN molecular rearrangements (YAP1, RELA, MAMLD1 and FAM118B), in 27 EPN patients from Pediatric Oncology Institute - GRAACC, Brazil. Gene expression levels were quantified using qPCR. Molecular findings were correlated to clinicopathological characteristics of patients. Significant results were considered when p<0.005. Overall survival was significantly lower in patients with PF tumors than ST tumors (p=0.0109), and high YAP1 expression was related to worst overall survival (p=0.0488). ST tumors presented higher RELA expression than PF tumors (p=0.0089). Expression of YAP1 and FAM118B genes significantly correlated (r=0.917, p<0.0001). All investigated genes are partners in fusion genes recently described for EPN and the levels of expression observed were in agreement with findings in the literature. Additional studies are in progress to collaborate with the characterization of EPN genetics, once development of targeted therapies will require the understanding of tumor biology and its effect in the clinical outcomes. Based on recent molecular findings, and after the actualization of WHO classification of tumors of the CNS in 2016, it is becoming evident that, in the near future, histologic criteria alone might be insufficient to direct treatment, to predict outcomes and refine EPN treatment.

IMMU-18. PDL-1 EXPRESSION ON CIRCULATING CD68 (-) MONOCYTE-LIKE CELLS IN NF2 MENINGIOMA AS A BIOMARKER FOR TUMOR PROGRESSION

Abstract

Program cell death ligand-1 (PD-L1) membranous expression on >5% tumor cells (PD-L1 positive tumors) is an unfavorable prognostic marker in many solid tumors. We previously showed that approximately 40% of neurofibromatosis type 2 (NF2) meningiomas are PD-L1 positive tumors. However, due to the invasive nature of biopsies, collection of tumor tissue is not always feasible. Thus, a non-invasive alternative is needed to evaluate the status of tumor growth and confirm PD-L1 positive tumors before the consideration of immunotherapy. It has recently been revealed that expression of PD-L1 on tumor associated macrophages is also a strong prognostic indicator. We retrieved formalin-fixed paraffin-embedded (FFPE) tissue from 10 NF2 meningioma cases to identify PD-L1 expression on macrophages and/or monocytes. We found that 3 out of 4 PD-L1 positive tumors were associated with expression of PDL-1 on CD68 (-) monocyte-like cells located in the peri- and intravascular lumens. These cells were only observed in 1 out of 6 PD-L1 negative tumors. Compared to others, tumors with PD-L1 expression on monocyte-like cells presented a higher Ki-67 proliferative index that was above 10%. Our results suggest that PD-L1 positive circulating CD68 (-) monocyte-like cells are correlated with tumor cell PD-L1 expression and progression in NF2 meningiomas.

An unusual erythematous plaque on the back of an elderly woman

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Spontaneous improvement of cutis verticis gyrata secondary to acromegaly following surgical treatment of pituitary adenoma

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Nodal pigmentation due to tattoo pigment does not influence survival of melanoma patients

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Patient acceptance and trust in automated computer‐assisted diagnosis of melanoma with dermatofluoroscopy

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Multiple exophytic tumors in an 80‐year‐old patient with chronic lymphocytic leukemia

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Treatment of acquired reactive perforating dermatosis – a systematic review

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Anti‐laminin 332 mucous membrane pemphigoid with laryngeal involvement – adjuvant treatment with immunoadsorption and rituximab

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Blepharitis caused by deep trichophytosis – tinea ciliaris

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Barriers and enablers to patient recruitment for randomised controlled trials on treatment of chronic wounds: A systematic review

International Wound Journal, EarlyView.

Epithelial sheath neuroma with extension to the subcutis

Journal of Cutaneous Pathology, EarlyView.

Hospitalised patients’ experiences during Negative Pressure Wound Therapy due to surgical site infection after vascular and cardiac surgery

International Wound Journal, EarlyView.

Contact allergy to oxidized geraniol among Swedish dermatitis patients—A multicentre study by the Swedish Contact Dermatitis Research Group

Contact Dermatitis, EarlyView.

Hydroa vacciniforme‐like lymphoproliferative disorder in an elderly Chinese patient and a literature review of adult cases

International Journal of Dermatology, EarlyView.

Necrotic cheek ulcer in a liver transplant patient

International Journal of Dermatology, EarlyView.

Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines†

Multiple lentigines arising on resolving psoriatic plaques after treatment with apremilast

Clinical and Experimental Dermatology, EarlyView.

Influence of foreign direct investment on indicators of environmental degradation

Abstract

This study aims to contribute to the existing literature by looking at the influence of foreign direct investment on carbon dioxide emissions, carbon footprint, and ecological footprint. In order to realize the aim of this study, we have utilized the augmented mean group estimator, which is supported by common correlated effect mean group estimator in the analysis for 20 countries. The panel results reveal that foreign direct investment has no effect on environmental degradation indicators. The panel results further reveal that gross domestic product, energy consumption, and urbanization are the main contributors to environmental degradation. The results at country level show that foreign direct investment and urbanization increase pollution in the developing countries while they mitigate pollution in the developed countries. Moreover, gross domestic product and energy consumption increase pollution for both developed and developing countries, which includes China and the USA. The negative impact of foreign direct investment on environmental degradation in the developed countries can be explained on the basis that these countries have strong environmental regulations, which makes it almost impossible for dirty foreign industries to invest therein. From the output of this research, several policy recommendations are enumerated for the investigated countries.

Management of posterior glottic stenosis using the Combined Glottic Reconstruction procedure

Clinical Otolaryngology, EarlyView.

Characteristics and pathogenesis of facial nerve stimulation after cochlear implant surgeries: A single‐centre retrospective analysis from 1151 patients

Clinical Otolaryngology, EarlyView.

Exposures to Volatile Organic Compounds among Healthcare Workers: Modeling the Effects of Cleaning Tasks and Product Use

Abstract

Objectives

Use of cleaning and disinfecting products is associated with work-related asthma among healthcare workers, but the specific levels and factors that affect exposures remain unclear. The objective of this study was to evaluate the determinants of selected volatile organic compound (VOC) exposures in healthcare settings.

Methods

Personal and mobile-area air measurements (n = 143) from 100 healthcare workers at four hospitals were used to model the determinants of ethanol, acetone, 2-propanol, d-limonene, α-pinene, and chloroform exposures. Hierarchical cluster analysis was conducted to partition workers into groups with similar cleaning task/product-use profiles. Linear mixed-effect regression models using log-transformed VOC measurements were applied to evaluate the association of individual VOCs with clusters of task/product use, industrial hygienists' grouping (IH) of tasks, grouping of product application, chemical ingredients of the cleaning products used, amount of product use, and ventilation.

Results

Cluster analysis identified eight task/product-use clusters that were distributed across multiple occupations and hospital units, with the exception of clusters consisting of housekeepers and floor strippers/waxers. Results of the mixed-effect models showed significant associations between selected VOC exposures and several clusters, combinations of IH-generated task groups and chemical ingredients, and product application groups. The patient/personal cleaning task using products containing chlorine was associated with elevated levels of personal chloroform and α-pinene exposures. Tasks associated with instrument sterilizing and disinfecting were significantly associated with personal d-limonene and 2-propanol exposures. Surface and floor cleaning and stripping tasks were predominated by housekeepers and floor strippers/waxers, and use of chlorine-, alcohol-, ethanolamine-, and quaternary ammonium compounds-based products was associated with exposures to chloroform, α-pinene, acetone, 2-propanol, or d-limonene.

Conclusions

Healthcare workers are exposed to a variety of chemicals that vary with tasks and ingredients of products used during cleaning and disinfecting. The combination of product ingredients with cleaning and disinfecting tasks were associated with specific VOCs. Exposure modules for questionnaires used in epidemiologic studies might benefit from seeking information on products used within a task context.

A Systematic Review of the Routes and Forms of Exposure to Engineered Nanomaterials

Abstract

Background

Establishing the routes of exposure is a fundamental component of the risk assessment process for every dangerous substance. The present study systematically reviews the available literature to assess the relevance of the different routes and forms of exposure that are of concern for the protection of workers during the manufacture, handling, or end-use of engineered nanomaterials (ENMs).

Methods

A systematic review of the peer-reviewed literature published between 2000 and 2015 was completed. Only studies including measurements of inhalation or dermal exposure were selected and used to identify the exposure situations for which the measurements were collected. The identified exposure situations were grouped based on the type of ENM (i.e. carbon nanotubes and fibres, silicon-based, titanium dioxide, other metal oxides, pure elemental metals, and other ENMs) and activity involved. The grouped exposure situations were assessed to provide a conclusion regarding the likelihood, form, and route of exposure. Assessment of the likelihood of exposure was based on well-defined criteria using a previously established decision logic for inhalation exposure and the outputs from measurements and/or conceptual models for dermal/ingestion exposure. For each combination of nano-activity and type of ENM, the aggregated likelihood across all relevant individual assessments was used to draw conclusions about the relevance of both the inhalation and dermal/ingestion routes. Based on the quality of the data, the strength of the evidence was also evaluated.

Results

One hundred and seven studies were identified during the review process, reporting 424 individual exposure assessments. Measurement data were limited for dermal/ingestion exposure and for inhalation exposure for downstream use and end-of-life. However, the data provided high-quality evidence that in occupational settings all three routes can be of relevance for exposure to ENMs. In general, whenever inhalation exposure occurs then dermal and inadvertent ingestion exposure may occur due to surface deposition and transfer due to the ENMs release. However, for some forms of exposure (e.g. suspension/liquids), dermal exposure can occur even when inhalation exposure is unlikely. An increased likelihood of exposure was observed for manual activities such as cleaning and maintenance, collection/harvesting, spraying, and finishing as well as those involving feeding into a process and handling of powders outside enclosures. The likelihood of exposure was affected by the presence of risk management measures and the scale of the production involved.

Conclusion

This literature review provides evidence that for ENMs, as found for other materials, the likelihood of the exposure depends largely on the physical form of the substance as well as the applied process and operational conditions. These results can be used to provide first indications of the likelihood of exposure and guidance for exposure controls in workplaces. However, there is a clear lack of high-quality exposure data, in particular for downstream use and end-of-life scenarios and in low- and medium-income countries.

Dysthyroid Optic Neuropathy

Purpose: Dysthyroid optic neuropathy (DON) is a serious complication of Graves orbitopathy that can result in irreversible and profound visual loss. Controversy exists regarding the pathogenesis and management of the disease. The authors provide an overview of the current understanding of DON and present a therapeutic guideline. Methods: A review of the literature. Results: The mechanism of DON appears to be multifactorial: direct compression of the optic nerve by enlarged extraocular muscles, stretching of the optic nerve by proptosis, orbital pressure, vascular insufficiency, and inflammation. Some or all of these factors may be involved in an individual patient. There has only been one controlled trial comparing high-dose intravenous methylprednisolone to bony orbital decompression for DON. Both 2-wall and 3-wall decompression techniques successfully improve visual functions of patients with DON. There are few case reports/case series that suggest biologic agents may improve visual function in DON. Conclusions: DON is a serious complication of Graves orbitopathy, the diagnosis and management of which is complex and requires a multidisciplinary approach. There is little evidence regarding the optimum management strategy. Based on the current literature, the first line of treatment is intravenous methylprednisolone, with the exact timing and indication of bony orbital decompression still to be determined. In addition, there may be a role for the use of biologic agents that will require a systematic program to determine efficacy. Accepted for publication April 5, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Peerooz Saeed, Academic Medical Center, Department of Ophthalmology, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. E-mail: p.saeed@amc.uva.nl © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Extraocular Muscle Enlargement and Thyroid Eye Disease-like Orbital Inflammation Associated with Immune Checkpoint Inhibitor Therapy in Cancer Patients

Purpose: To describe thyroid eye disease (TED)-like orbital inflammatory syndrome in 3 cancer patients treated with immune checkpoint inhibitors. Methods: All consecutive patients treated by the senior author who were receiving immune checkpoint inhibitors and developed TED-like orbital inflammation were included. Results: Three cancer patients treated with immune checkpoint inhibitors developed orbital inflammation. The first patient was treated with a combination of a cytotoxic T-lymphocyte antigen-4 inhibitor and a programmed cell death protein 1 inhibitor and developed TED-like orbital inflammation with normal thyroid function and antibody levels. The second patient had a previous diagnosis of Graves disease without TED, and developed TED soon after initiating treatment with a programmed cell death protein 1 inhibitor. The third patient developed acute hyperthyroidism with symptomatic TED following treatment with an investigational cytotoxic T-lymphocyte antigen-4 inhibitor agent. All 3 patients were managed with either systemic steroids or observation, with resolution of their symptoms and without the need to halt immune checkpoint inhibitor treatment for their cancer. Discussion and Conclusions: TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti–cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction. Accepted for publication May 1, 2018. Part of this work was presented at the International Thyroid Eye Disease Symposium on June 24, 2016 in London, United Kingdom. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Bita Esmaeli, M.D., F.A.C.S., Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, Unit 1488, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E-mail: besmaeli@mdanderson.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Cultures of Proximal and Distal Segments of Silicone Tubes After Dacryocystorhinostomy

Purpose: To compare the results of cultures of the proximal and distal segments of silicone tubes after dacryocystorhinostomy. Methods: The medical records of patients undergoing a dacryocystorhinostomy and silicone intubation were reviewed. The inclusion criteria were cultures of both distal and proximal stent segments after removal, dye testing, evaluation of the tear meniscus, and notation of the presence or absence of discharge before and after removal. The exclusion criteria included the use of systemic or topical antibiotics within 1 month before tube removal. Results: Forty-six lacrimal systems in 40 patients were included, with 6 patients having bilateral dacryocystorhinostomies. There were no cases of dacryocystitis at the time of or after tube removal. Four (9%) of the dacryocystorhinostomies failed. Forty-one (89%) of the distal tube segments had positive cultures. The distal tube cultures grew 17 (36%) gram-positive bacteria, 21 (45%) gram-negative bacteria, 7 (15%) skin flora, and 2 (4%) fungi (6 distal segments had mixed cultures). Thirteen (28%) of the proximal tube segments had positive cultures. The proximal tube cultures were 5 (38%) gram-negative bacteria, 4 (31%) gram-positive bacteria, 3 (23%) skin flora, and 1 (8%) acid-fast bacteria. Four (31%) of the proximal tubes with positive cultures grew the same organism as the distal tube segment. Nine (69%) of the proximal tubes with positive cultures grew different organisms than the distal segment. Forty-two (91%) of all the proximal tube cultures were either negative or grew different organisms than the distal segment cultures. Conclusions: The proximal segment of a silicone tube after a dacryocystorhinostomy may be a "privileged" area. There is usually a lack of growth or the growth of different organisms than those present on the distal tube segments. This may be explained by the protective nature of the tear film. The findings may also help to explain the low incidence of dacryocystitis in spite of the growth of virulent organisms on the distal tube segment after a dacryocystorhinostomy. Accepted for publication April 11, 2018. B.B.B. receives royalties for the StenTube. The author has no conflicts of interest to disclose. Address correspondence and reprint requests to Bruce B. Becker, M.D., 5363 Balboa Boulevard, Suite 246, Encino, CA 91316. E-mail: Bresbii@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Prediction and optimization of CI engine performance fuelled with Calophyllum inophyllum diesel blend using response surface methodology (RSM)

Abstract

The transportation demand in India is increasing tremendously, which arouses the energy consumption by 4.1 to 6.1% increases each year from 2010 to 2050. In addition, the private vehicle ownership keeps on increasing almost 10% per year during the last decade and reaches 213 million tons of oil consumption in 2016. Thus, this makes India the third largest importer of crude oil in the world. Because of this problem, there is a need of promoting the alternative fuels (biodiesel) which are from different feedstocks for the transportation. This alternative fuel has better emission characteristics compared to neat diesel, hence the biodiesel can be used as direct alternative for diesel and it can also be blended with diesel to get better performance. However, the effect of compression ratio, injection timing, injection pressure, composition-blend ratio and air-fuel ratio, and the shape of the cylinder may affect the performance and emission characteristics of the diesel engine. This article deals with the effect of compression ratio in the performance of the engine while using Honne oil diesel blend and also to find out the optimum compression ratio. So the experimentations are conducted using Honne oil diesel blend-fueled CI engine at variable load conditions and at constant speed operations. In order to find out the optimum compression ratio, experiments are carried out on a single-cylinder, four-stroke variable compression ratio diesel engine, and it is found that 18:1 compression ratio gives better performance than the lower compression ratios. Engine performance tests were carried out at different compression ratio values. Using experimental data, regression model was developed and the values were predicted using response surface methodology. Then the predicted values were validated with the experimental results and a maximum error percentage of 6.057 with an average percentage of error as 3.57 were obtained. The optimum numeric factors for different responses were also selected using RSM.