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Goblet cell hyperplasia and overproduction of airway mucin are characteristic features of the lung epithelium of smokers and COPD patients. Tobacco heating products (THPs) are a potentially less risky alternative to combustible cigarettes, and through continued use solus THPs may reduce smoking-related disease risk. Using the MucilAir™ in vitro lung model, a 6-week feasibility study was conducted investigating the effect of repeated cigarette smoke (1R6F), THP aerosol and air exposure. Tissues were exposed to nicotine-matched whole aerosol doses 3 times/week. Endpoints assessed were dosimetry, tight-junction integrity, cilia beat frequency (CBF) and active area (AA), cytokine secretion and airway mucin MUC5AC expression. Comparison of incubator and air exposed controls indicated exposures did not have a significant effect on the transepithelial electrical resistance (TEER), CBF and AA of the tissues. Cytokine secretion indicated clear differences in secretion patterns in response to 1R6F and THP exposure. 1R6F exposure resulted in a significant decrease in the TEER and AA (p=0.000 and p=0.000, respectively), and an increase in MUC5AC positive cells (p=0.002). Repeated THP exposure did not result in a significant change in MUC5AC positive cells. This study demonstrates repeated cigarette smoke whole aerosol exposure can induce these morphological changes in vitro.

Reservoir sedimentation constitutes a major issue worldwide and a long-lasting priority for dam managers, especially when hydropower, and hence profit, is involved. Commonly, the problem of excessive sedimentation is attributed to failed prediction of the sediment supply from the upland basin prior to the construction of dams, namely to the underestimation of sediment inflow to the reservoir.The sediment input in the Rio di Pusteria reservoir (South Tyrol, Italy) between two consecutive sediment flushing operations in June 2014 and May 2019, was determined by obtaining the volumetric difference between very high resolution (0.25 m) reservoir bathymetries conducted after the flushing of 2014 and before the flushing of 2019. The sediment yield in the reservoir during the latter period was found to be 453,783 t.To calculate the sediment yield in the reservoir, we have applied a gridded seven-factor Universal Soil Loss Equation (USLE) combined with a Sediment Delivery Ratio (SDR) module in a high resolution (2.5 m) GIS environment, which enabled an accurate representation of the rapidly shifting Alpine topography. An additional factor for coarse fragments was added to the conventional six-factor USLE to account for the non-erodible part of the basin. This is of great importance as the USLE-based models are criticized to produce extreme erosion rates in uplands and mountain areas. The topographic factor, LS, was refined by the use of a fine scale DEM and the slope length factor, L, was adjusted to the Alpine terrain by means of a regulating threshold. The proposed SDR module does not rely on one but on several physiographic, topographic and hydrologic characteristics of the basin. Finally, the rainfall erosivity factor, R, was determined in two different ways, one representing the rainfall climatology of the study area and one the specific rainfall conditions of the study period, hence the application of the model in two distinct configurations.The application of the combined USLE-SDR model resulted in five-year reservoir sedimentation rates of 439,279.2 t and 589,520.5 t, with deviations from the measured sediment yield of 3.3% and -25.5%. Excluding very high altitudes with glaciers and perennial snow, we consider the proposed modeling approach ideal for upper lands and mountainous areas such as the Alps.

Mucus hypersecretion contributes to lung function impairment observed in COPD (chronic obstructive pulmonary disease), a tobacco smoking-related disease. A detailed mucus hypersecretion adverse outcome pathway (AOP) has been constructed from literature reviews, experimental and clinical data, mapping key events (KEs) across biological organisational hierarchy leading to an adverse outcome. AOPs can guide the development of biomarkers that are potentially predictive of diseases and support the assessment frameworks of nicotine products including electronic cigarettes. Here, we describe a method employing manual literature curation supported by a focused automated text mining approach to identify genes involved in 5 KEs contributing to decreased lung function observed in tobacco-related COPD. KE genesets were subsequently confirmed by unsupervised clustering against 3 different transcriptomic datasets including (1) in vitro acute cigarette smoke and e-cigarette aerosol exposure, (2) in vitro repeated incubation with IL-13, and (3) lung biopsies from COPD and healthy patients. The 5 KE genesets were demonstrated to be predictive of cigarette smoke exposure and mucus hypersecretion in vitro, and less conclusively predict the COPD status of lung biopsies. In conclusion, using a focused automated text mining and curation approach with experimental and clinical data supports the development of risk assessment strategies utilising AOPs.

A novel application of spline curves was developed for tracing average daily trends of water demand. These trends were used as input of a stochastic model to generate synthetic time series ...

Objectives Cigarette smoke aqueous aerosol extracts (AqE) have been used for assessing tobacco products, particularly with in vitro models such as oxidative stress and inflammation. These test articles can be generated easily, but there are no standardised methods for the generation and characterisation or stability. We investigated the effects of pro-oxidant smoke-derived chemicals by using 3R4F AqE generated under standardised conditioning and smoking regimes and assessed the stability over 31-week timeframe. Twenty batches generated from ten puffs per cigarette bubbled through 20 ml cell culture media were used fresh and thawed from frozen aliquots stored at – 80 ºC. Results Nicotine levels quantified by gas chromatography/mass spectrometry and optical density at 260 nm showed chemical and physical stability from week 0 (fresh sample) to weeks 1, 4, 8 and 31 (frozen samples). No significant change in H292 human bronchial epithelial cell viability or oxidative stress were observed between fresh AqE at week 0 and frozen AqE at 31 weeks. AqEs generated by our protocol were stable for up to 31 weeks for all tested end points, suggesting that it may not be necessary to use freshly generated AqE for each study, thus reducing batch-to-batch variability.

Tobacco-free ‘modern’ oral nicotine pouches (MOPs), are similar in appearance and use to Swedish-style snus, but without tobacco. There are few identified methods to create test samples for toxicologically assessment of MOPs in vitro. In this study we present a simple method for the extraction of pouch material in cell culture media, providing consistent nicotine concentration and easy in vitro assessment. A series of contemporary in vitro screening assays (viability, cell health markers, oxidative stress and genotoxicity) using human oral fibroblasts (HGF) and human lung epithelial cells (H292) were employed. Extracts were generated from LYFT and compared to snus (CRP1.1) and cigarette (1R6F) reference products. MOP and CRP1.1 extracts were generated by incubating one pouch in 20 ml of cell culture media, while 1R6F AqE was prepared by smoking 1 cigarette into 20 ml of cell culture media. 1R6F demonstrated toxicological responses in most assays; CRP1.1 had minimal to moderate effects while MOP demonstrated little or no response in all assays. This study demonstrated the generation of MOPs extracts and their toxicological evaluation using in vitro screening approaches. Future product usage, pharmacokinetics and clinical studies will further substantiate the reduced risk potential of MOPs.

Tobacco heating products (THPs) represent a subset of the next-generation nicotine and tobacco product category, in which tobacco is typically heated at temperatures of 250-350 °C, thereby avoiding many of the harmful combustion-related toxicant emissions of conventional cigarettes. In this study, we have assessed aerosol generation and cytotoxicity from two commercially available THPs, THP1.0 and THS, relative to tobacco smoke from 3R4F reference cigarettes, using an adapted Borgwaldt RM20S Smoking Machine. Quantification of nicotine in the exposed cell-culture media showed greater delivery of nicotine from both THPs than from the cigarette. Using Neutral Red Uptake assay, THPs demonstrated reduced in vitro cytotoxicity in H292 human bronchial epithelial cells as compared with 3R4F cigarette exposure at the air-liquid interface (p 0.0001). Both THPs demonstrated a statistically similar reduction in biological response, with87% viability relative to 3R4F at a common aerosol dilution (1:40, aerosol:air). A similar response was observed when plotted against nicotine; a statistical difference between 3R4F and THPs (p 0.0001) and no difference between the THPs (p = 0.0186). This pre-clinical in vitro biological testing forms part of a larger package of data to help assess the safety and risk reduction potential of next-generation tobacco products relative to cigarettes, using a weight of evidence approach.

Sedimentation in reservoirs constitutes a major issue worldwide, especially when hydropower, and hence profit, is involved. In this study, the sedimentation rates, due to soil erosion and sediment yields, are analyzed in the reservoir of the Rio di Pusteria hydropower dam, in South Tyrol (Italian Alps). The focus is on a five-year period, between two consecutive sediment flushing operations occurred in June 2014 and May 2019. Based on the difference between the pre- and post-flushing bathymetries, the five-year aggregated sediment yield was determined. The soil erosion from the basin surface and the sediment budget in the reservoir are calculated by means of a gridded Universal Soil Loss Equation (USLE), combined with a Sediment Delivery Ratio (SDR) module. The topographic factor is improved by the use of a fine-scale DEM and the slope length factor is adjusted to the Alpine terrain by means of a fitting threshold. The rainfall erosivity factor is determined in two different ways, one representing the precipitation regime of the study area and one the specific rainfall conditions of the study period. The two different applications result to calculated reservoir sedimentation rates of 439,279.2 tons and 589,520.5 tons with deviations from the measured value of 3.1% and −23.2%, respectively, while the sediment delivery ratio to the reservoir was found to be 12.5%. The calculations are also compared with results of the application of the conventional six-factor USLE. The comparison between calculations and measurements shows that the methods used can be efficiently applied in an Alpine basin for the estimation of reservoir sedimentation rates.

In water networks characterized by a significant variation in ground elevations the necessity of pumping water in some areas is complicated by a conflicting requirement to reduce excess pressures in other areas. This and the increasing cost of electricity has led to the use of Pumps-operating-As-Turbines (PATs) devices that can reduce pressure (and leakage) whilst harvesting energy. This paper presents a methodology for optimal water distribution system (WDS) management, driving the optimization by minimizing the surplus pressure at network nodes and the operational pumping costs and maximizing the income generated through energy recovery. The method is based on a highly parallelized Evolutionary Algorithm, employing an hydraulic solver to evaluate hydraulic constraints. Water demands at network nodes are considered as uncertain variables modelled by using a probabilistic approach in order to take into account unknown future demands. The approach is demonstrated in different case studies. Results obtained highlight that the economic benefits of installing PATs for energy recovery in conjunction with a combined pump-scheduling and pressure management regime is especially related to the input network characteristics. Further analysis of the importance of the probabilistic approach and of the influence of the interval time step adopted for the optimization has been evaluated.

This study assessed the toxicological and biological responses of aerosols from a novel hybrid tobacco product. Toxicological responses from the hybrid tobacco product were compared to those from a commercially available Tobacco Heating Product (c-THP), a prototype THP (p-THP) and a 3R4F reference cigarette, using in vitro test methods which were outlined as part of a framework to substantiate the risk reduction potential of novel tobacco and nicotine products. Exposure matrices used included total particulate matter (TPM), whole aerosol (WA), and aqueous aerosol extracts (AqE) obtained after machine-puffing the test products under the Health Canada Intense smoking regime. Levels of carbonyls and nicotine in these matrices were measured to understand the aerosol dosimetry of the products. The hybrid tobacco product tested negative across the in vitro assays including mutagenicity, genotoxicity, cytotoxicity, tumour promotion, oxidative stress and endothelial dysfunction. All the THPs tested demonstrated significantly reduced responses in these in vitro assays when compared to 3R4F. The findings suggest these products have the potential for reduced health risks. Further pre-clinical and clinical assessments are required to substantiate the risk reduction of these novel products at individual and population levels.

Peak water demand is one of the most stringent operative conditions for a Water Distribution System (WDS), not only for the intensity of the event itself, but also for its recurring nature. The estimation of the maximum water demand is a crucial aspect in both the design and management processes. Studies in the past have tackled this issue with deterministic approaches, even if peak phenomena are distinctly random. In this work, probabilistic models have been developed to study and forecast the daily maximum residential water demand. Some probability distributions have been tested by means of statistical inferences on different data samples related to three monitored WDS. The parameter estimations of the proposed equations have been related to the number of supplied users. Furthermore, this work investigates time scaling effects on the effectiveness of the proposed distributions and relations. Corrective factors that take into account the effect of time averaging step on the above-mentioned parameters have been proposed.