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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.

Graphical abstract, We have developed a novel vaping product (NVP) IS1.0(TT), which utilises a stainless-steel mesh to transfer and vaporise the e-liquid, mitigating some of the potential sources of toxicants that can be generated using the more traditional ‘wick and coil’ approach. The emissions from IS1.0(TT) have previously been found to have lower levels of toxicants overall when directly compared with a commercial wick and coil e-cig. This current study assessed the toxicological responses to aerosols from this NVP. Responses induced by IS1.0(TT)were compared to those from a 3R4F reference cigarette, using in vitro test methods which included regulatory genetic toxicological assays as well as some more contemporary screening approaches. The experimental conditions were designed to facilitate the testing of aerosol from this vaping product at doses that in most cases greatly exceeded those of the 3R4F comparator showed little to no toxicological responses and demonstrated significantly reduced effects in these in vitro assays when compared to 3R4F. Furthermore, the extreme doses tested in the present study indicate that the toxicant profile of this NVP translates to lower biological activity in vitro, and suggests that the absolute risk hazard level associated with electronic cigarettes can be reduced through continuous improvement as the technology evolves.

In recent years, pressure-driven analyses of water distribution systems using pressure-flow relationships (PFRs) were shown to be more computationally efficient than those based on flow-pre...

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 ...

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.

International audience; The paper presents the results of the Battle of Postdisaster Response and Restoration (BPDRR) presented in a special session at the first International water distribution systems analysis & computing and control in the water industry (WDSA/CCWI) Joint Conference, held in Kingston, Ontario, Canada, in July 2018. The BPDRR problem focused on how to respond and restore water service after the occurrence of five earthquake scenarios that cause structural damage in a water distribution system. Participants were required to propose a prioritization schedule to fix the damages of each scenario while following restrictions on visibility/nonvisibility of damages. Each team/approach was evaluated against six performance criteria: (1)time without supply for hospital/firefighting, (2)rapidity of recovery, (3)resilience loss, (4)average time of no user service, (5)number of users without service for eight consecutive hours, and (6)water loss. Three main types of approaches were identified from the submissions: (1)general-purpose metaheuristic algorithms, (2)greedy algorithms, and (3)ranking-based prioritizations. All three approaches showed potential to solve the challenge efficiently. The results of the participants showed that for this network, the impact of a large-diameter pipe failure on the network is more significant than several smaller pipes failures. The location of isolation valves and the size of hydraulic segments influenced the resilience of the system during emergencies. On average, the interruptions to water supply (hospitals and firefighting) varied considerably among solutions and emergency scenarios, highlighting the importance of private water storage for emergencies. The effects of damages and repair work were more noticeable during the peak demand periods (morning and noontime) than during the low-flow periods; and tank storage helped to preserve functionality of the network in the first few hours after a simulated event.

Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products.

A correct water demand characterization is at the base of a reliable water distribution system simulation. The stochastic nature of water demand is well established and thus has to be addressed. In the present work a methodology to generate synthetic demand patterns interpolating known points by means of piecewise interpolation has been implemented in Python. Subsequently a stochastic approach has been applied to the interpolated demand patterns, which is based on a mixed probability distribution. Such approach considers the dual nature of water demand as continuous and discrete random variable, in order to contemplate both the event of it being null and not null. The needed parameters are obtainable through simple equations depending solely on the number of served users.

The aging process in water distribution system is one of the main drivers for the reduction of performances in water distribution systems. Furthermore, this conditions usually imply an increase in the maintenance costs that the water utilities have to sustain. In this situation it is required to undertake programmatic strategies in order to guarantee the highest benefit for both the final users and the water companies. An optimal rehabilitation strategy has been proposed in order to take into account the regulatory schemes that have to be abided at the national level, in the water industry.

Water demand characterization when this assumes minimum values, if not null ones, is of fundamental importance for the hydraulic network management analysis. In fact, when this water demand condition occurs – usually during the night time – maximum pressures are on network pipes and at the same time tank levels increase and treatment plants are supplied with the minimum flow. The study of the null water demand are furthermore of great interest for leakages analysis in water complex systems. In this paper a study of the probability of null residential demand is provided by referring to different case studies in which the number of users ranges between 500-1250. In order to be able of implementing this study in a water distribution modeling, relationships for the daily null water demand characterization in function of the users supplied and the interval time discretization are also proposed.

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.

Side weirs have been used for centuries in urban drainage and flood control for their ability to divert high incoming flow rates. The flow along a side weir may be studied by means of different approaches. However, although the question of side weir has been debating for many decades, there are few studies on the local hydraulic characteristics of the flow along these structures in circular channels. An experimental study of the flow field in a circular channel along a side weir using a commercial TSI Particle Image Velocimetry (PIV) system is shown in this paper. Weakly supercritical flows running into different geometric configurations of the weir were investigated, with Froude numbers varying from 1.1 to 1.6. Free surface profiles have been obtained by an image processing technique. An empirical equation has been proposed for their representation. Longitudinal velocity profiles along the side weir can be well predicted by an entropic approach. Local outflow along the side weir may be represented by an asymmetric curve. The peak outflow generally occurs between the 30% and the 50% of the weir length. The elementary discharge coefficient significantly increases from upstream to downstream. An energy head reduction was observed under the investigated configurations. Most of the head variation occurs in the central part of the weir. Finally, the flow power decreases along the weir according to a non-linear function. A thorough knowledge of the flow field features should allow to improve side weir analysis and design, whatever approach is used for the study.

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.