Increased AXLhigh myeloid cells as pathognomonic marker in Langerhans cell histiocytosis and Langerin expression dependence of mTOR inhibition.

Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

Monitoring Circulating CD207+CD1a+ Cells in Langerhans Cell Histiocytosis and Clinical Implications.

Langerhans cell histiocytosis (LCH) is a disorder characterized by an abnormal accumulation of CD207+ and CD1a+ cells in almost any tissue. Currently, there is a lack of prognostic markers to follow up patients and track disease reactivation or treatment response. Putative myeloid precursors CD207+ and CD1a+ cells were previously identified circulating in the blood. Therefore, we aim to develop a sensitive tracing method to monitor circulating CD207+ and CD1a+ cells in a drop of blood sample of patients with LCH. A total of 202 blood samples from patients with LCH and 23 controls were tested using flow cytometry. A standardized cellular score was defined by quantifying CD207+ and CD1a+ expression in monocytes and dendritic cells, based on CD11b, CD14, CD11c, and CD1c subpopulations, resulting in a unique value for each sample. The scoring system was validated by a receiver operating characteristic curve showing a reliable discriminatory capacity (area under the curve of 0.849) with a threshold value of 14, defining the presence of circulating CD207+ and CD1a+ cells. Interestingly, a fraction of patients with no evident clinical manifestation at the time of sampling also showed presence of these cells (29.6%). We also found a differential expression of CD207 and CD1a depending on the organ involvement, and a positive correlation between the cellular score and plasma inflammatory markers such as soluble CD40L, soluble IL-2Ra, and CXCL12. In conclusion, the analysis of circulating CD207 and CD1a cells in a small blood sample will allow setting a cellular score with minimal invasiveness, helping with prognostic accuracy, detecting early reactivation, and follow-up.

Modeled and measured SARS-CoV-2 virus in septic tank systems for wastewater surveillance.

SARS-CoV-2 wastewater surveillance (WWS) at wastewater treatment plants (WWTPs) can reveal sewered community COVID-19 prevalence. For unsewered areas using septic tank systems (STSs) or holding tanks, how to conduct WWS remains unexplored. Here, two large STSs serving Zuma Beach (Malibu, CA) were studied. Supernatant and sludge SARS-CoV-2 concentrations from the directly-sampled STSs parameterized a dynamic solid-liquid separation, mass balance-based model for estimating the infection rate of users. Pumped septage before hauling and upon WWTP disposal was also sampled and assessed. Most (96%) STS sludge samples contained SARS-CoV-2 N1 and N2 genes, with concentrations exceeding the supernatant and increasing with depth while correlating with total suspended solids (TSS). The trucked septage contained N1 and N2 genes which decayed (coefficients: 0.09-0.29 h-1) but remained detectable. Over approximately 5 months starting in December 2020, modeled COVID-19 prevalence estimations among users ranged from 8 to 18%, mirroring a larger metropolitan area for the first 2 months. The approaches herein can inform public health intervention and augment conventional WWS in that: (1) user infection rates for communal holding tanks are estimable and (2) pumped and hauled septage can be assayed to infer where disease is spreading in unsewered areas.

How elevation dictates technology selection in biological wastewater treatment.

Most wastewater treatment facilities are built using procedures from previous designs which are predominantly from sites and regions not located at high elevation. Recognizing this limitation, we assessed the effects of elevation above sea level on the suitability of process configurations and technologies as well as their associated energy costs. Using the International Water Association (IWA) benchmark simulation model No. 2 (modified Ludzack-Ettinger process layout) as a reference, we simulated scenarios including different activated sludge process configurations, operating under different environmental and process conditions. In order to include a wide sample of environmental conditions, data on atmospheric pressure, wastewater temperature, air temperature, and relative humidity (for average, warmest, and coldest months) were collected from municipal wastewater treatment plants located at different latitudes and elevations. The results confirm that elevation is a driver against the selection of diffused aeration technologies. Aeration costs for aerobic wastewater treatment are highly influenced by local project conditions, particularly by elevation and wastewater temperature, which together influence the driving force for oxygen transfer into water. When the driving force is low, operating costs are high. Recommendations for designing treatment processes effectively, including diffused aeration systems operating at high elevations above sea level, are proposed.

Soft Sensing for On-Line Fault Detection of Ammonium Sensors in Water Resource Recovery Facilities.

The increasing demand for online sensors applied to advanced control strategies in water resource recovery facilities has resulted in the increasing investigation of fault-detection methods to improve the reliability of sensors installed in harsh environments. The study herein focuses on the fault detection of ammonium sensors, especially for effluent monitoring, given their potential in ammonium-based aeration control applications. An artificial neural network model was built to predict the ammonium content in the effluent by employing the information from five other sensors installed in the activated sludge tank: NH4+, pH, ORP, DO, and TSS. The residual between the model prediction and the effluent ammonium sensor signal was utilized in a fault-detection mechanism based on principal component analysis and Shewhart monitoring charts. In contrast to previous studies, the present work utilizes typical faults collected from a 1 year historic dataset of an actual sensor setup. Treatment process anomalies, calibration bias faults, and fouling drifts were the most common issues identified from the historic dataset, and they were promptly identified by the proposed fault-detection methodology. Once a fault is detected, the model prediction can be actively used in place of the sensor for process control without affecting the treatment process by utilizing faulty datasets.

Comparison of methods for nitrous oxide emission estimation in full-scale activated sludge.

Nitrous oxide (N2O) gas transfer was studied in a full-scale process to correlate liquid phase N2O concentrations with gas phase N2O emissions and compare methods of determining the volumetric mass transfer coefficient, KLa. Off-gas and liquid phase monitoring were conducted at the Viikinmäki wastewater treatment plant (WWTP) over a two-week period using a novel method for simultaneous measurement of dissolved and off-gas N2O and O2 from the same location. KLa was calculated with three methods: empirically, based on aeration superficial velocity, from experimentally determined O2 KLa, and using a static value of best fit. The findings of this study indicated trends in local emitted N2O consistently matched trends in local dissolved N2O, but the magnitude of N2O emissions could not be accurately estimated without correction. After applying a static correction factor, the O2 method, using experimentally determined O2 KLa, provided the best N2O emission estimation over the data collection period. N2O emissions estimated using the O2 method had a root mean square error (RMSE) of 70.5 compared against measured concentrations ranging from 3 to 1,913 ppm and a maximum 28% error. The KLa value, and therefore the method of KLa determination, had a significant impact on estimated emissions.

The Fourth-Revolution in the Water Sector Encounters the Digital Revolution.

The so-called fourth revolution in the water sector will encounter the Big data and Artificial Intelligence (AI) revolution. The current data surplus stemming from all types of devices together with the relentless increase in computer capacity is revolutionizing almost all existing sectors, and the water sector will not be an exception. Combining the power of Big data analytics (including AI) with existing and future urban water infrastructure represents a significant untapped opportunity for the operation, maintenance, and rehabilitation of urban water infrastructure to achieve economic and environmental sustainability. However, such progress may catalyze socio-economic changes and cross sector boundaries (e.g., water service, health, business) as the appearance of new needs and business models will influence the job market. Such progress will impact the academic sector as new forms of research based on large amounts of data will be possible, and new research needs will be requested by the technology industrial sector. Research and development enabling new technological approaches and more effective management strategies are needed to ensure that the emerging framework for the water sector will meet future societal needs. The feature further elucidates the complexities and possibilities associated with such collaborations.

CD207+CD1a+ cells circulate in pediatric patients with active Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disease with an unknown etiology characterized by heterogeneous lesions containing CD207+CD1a+ cells that can arise in almost any tissue and cause significant morbidity and mortality. Precursors of pathological Langerhans cells have yet to be defined. Our aim was to identify circulating CD207+CD1a+ cells and their inducers in LCH. Expression of CD207 and CD1a in the blood myeloid compartment as well as thymic stromal lymphopoietin (TSLP) and transforming growth factor ß (TGF-ß) plasma levels were measured in 22 pediatric patients with active disease (AD) or nonactive disease (NAD). In patients with AD vs those with NAD, the myeloid compartment showed an increased CD11b (CD11bhigh plus CD11b+) fraction (39.7 ± 3.6 vs 18.6 ± 1.9), a higher percentage of circulating CD11bhighCD11c+CD207+ cells (44.5 ± 11.3 vs 3.2 ± 0.5), and the presence of CD11chighCD207+CD1a+ cells (25.0 ± 9.1 vs 2.3 ± 0.5). Blood CD207+CD1a+ cells were not observed in adult controls or umbilical cord. Increased TSLP and TGF-ß levels were detected in patients with AD. Interestingly, plasma from patients with AD induces CD207 expression on CD14+ monocytes. We conclude that CD207+CD1a+ cells are circulating in patients with active LCH, and TSLP and TGF-ß are potential drivers of Langerhans-like cells in vivo.

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P =020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly.

Winery wastewater treatment: a critical overview of advanced biological processes.

Wine production is one of the leading sectors of the food processing industry. The wine industry produces a large amount of wastewater characterized by a high strength in terms of organic pollution and large variability throughout the year. Most of the organic matter is soluble and easily biodegradable. On the other hand, nitrogen and phosphorous are lacking. The aerobic and anaerobic processes are largely applied for winery wastewater treatment because they can quickly react to changes in the organic loading. This review analyzes e applied biological systems, considering both aerobic and anaerobic processes, and different reactor configurations. The performances of different biological processes are evaluated in terms of operational conditions (organic loading rate and hydraulic retention time). Aerobic processes can guarantee chemical oxygen demand removal up to 98% for organic loading rates of some 1-2 kg of chemical oxygen demand m-3d-1 but requires good aeration systems to supply the required process oxygen. The management cost of these processes could be high considering the power density in the range 60-70 W m-3reactor and that nutrients should be added to support biomass growth. On the other hand, anaerobic processes are able to face high organic loads with low running costs, but COD removal is generally limited to 90%. Combination of the two treatment systems (anaerobic followed by aerobic) could reduce management costs and meet high discharge standards.

Modelling gas-liquid mass transfer in wastewater treatment: when current knowledge needs to encounter engineering practice and vice versa.

Gas-liquid mass transfer in wastewater treatment processes has received considerable attention over the last decades from both academia and industry. Indeed, improvements in modelling gas-liquid mass transfer can bring huge benefits in terms of reaction rates, plant energy expenditure, acid-base equilibria and greenhouse gas emissions. Despite these efforts, there is still no universally valid correlation between the design and operating parameters of a wastewater treatment plant and the gas-liquid mass transfer coefficients. That is why the current practice for oxygen mass transfer modelling is to apply overly simplified models, which come with multiple assumptions that are not valid for most applications. To deal with these complexities, correction factors were introduced over time. The most uncertain of them is the α-factor. To build fundamental gas-liquid mass transfer knowledge more advanced modelling paradigms have been applied more recently. Yet these come with a high level of complexity making them impractical for rapid process design and optimisation in an industrial setting. However, the knowledge gained from these more advanced models can help in improving the way the α-factor and thus gas-liquid mass transfer coefficient should be applied. That is why the presented work aims at clarifying the current state-of-the-art in gas-liquid mass transfer modelling of oxygen and other gases, but also to direct academic research efforts towards the needs of the industrial practitioners.

The future of WRRF modelling - outlook and challenges.

The wastewater industry is currently facing dramatic changes, shifting away from energy-intensive wastewater treatment towards low-energy, sustainable technologies capable of achieving energy positive operation and resource recovery. The latter will shift the focus of the wastewater industry to how one could manage and extract resources from the wastewater, as opposed to the conventional paradigm of treatment. Debatable questions arise: can the more complex models be calibrated, or will additional unknowns be introduced? After almost 30 years using well-known International Water Association (IWA) models, should the community move to other components, processes, or model structures like 'black box' models, computational fluid dynamics techniques, etc.? Can new data sources - e.g. on-line sensor data, chemical and molecular analyses, new analytical techniques, off-gas analysis - keep up with the increasing process complexity? Are different methods for data management, data reconciliation, and fault detection mature enough for coping with such a large amount of information? Are the available calibration techniques able to cope with such complex models? This paper describes the thoughts and opinions collected during the closing session of the 6th IWA/WEF Water Resource Recovery Modelling Seminar 2018. It presents a concerted and collective effort by individuals from many different sectors of the wastewater industry to offer past and present insights, as well as an outlook into the future of wastewater modelling.

The Economics of Wastewater Treatment Decentralization: A Techno-economic Evaluation.

The existing wastewater treatment infrastructure has not adequately established an efficient and sustainable use of energy, water, and nutrients. A proposed scheme based on source separation and water-efficient use is compared to the current wastewater management paradigm (one largely based on activated sludge) using techno-economic terms. This paper explores the economic viability of adopting more sustainable management alternatives and expands the understanding of the economics of decentralization and source-separation. The feasibility of three different potential types of source-separation (with different levels of decentralization) are compared to the conventional centralized activated sludge process by using recognized economic assessment methodologies together with widely accepted modeling tools. The alternatives were evaluated for two common scenarios: new developments and retrofit due to the aging of existing infrastructures. The results prove that source-separated alternatives can be competitive options despite existing drawbacks (only when countable incomes are included), while the hybrid approach resulted in the least cost-effective solution. A detailed techno-economic evaluation of the costs of decentralization provides insight into the current constraints concerning the paradigm shift and the cost of existing technologic inertia.

A Critical Review of the Factors Affecting Modeling Oxygen Transfer by Fine-Pore Diffusers in Activated Sludge.

In this review, the factors affecting the transfer of oxygen in activated sludge processes using fine-pore diffusers for water resource recovery are critically discussed. In water resource recovery facilities, the energy required for aeration constitutes 50% to 80% of the total energy consumed by the plant. This critical review highlights the use of fine-pore diffuser aeration and emphasizes the significance of accounting for the following factors: diffuser aging and fouling, diffuser layout, diffuser type, selector benefits, local environmental conditions (temperature and atmospheric pressure), influent wastewater variability, dissolved oxygen control systems, and airflow rates. In our review, we were unable to find mathematical models that could be used to develop dynamic α-factor predictions and diffuser fouling predictions. Although the development of a model that considers all the factors that affect oxygen transfer efficiency (OTE) in activated sludge systems would be extremely valuable, the creation of such a model is outside the scope of this review.

Energy footprint and carbon emission reduction using off-the-grid solar-powered mixing for lagoon treatment.

Mixing is the driver for the energy footprint of water resource recovery in lagoons. With the availability of solar-powered equipment, one potential measure to decrease the environmental impacts of treatment is to transition to an off-the-grid treatment. We studied the comparative scenarios of an existing grid-powered mixer and a solar-powered mixer. Testing was conducted to monitor the water quality, and to guarantee that the effluent concentrations were maintained equally between the two scenarios. Meanwhile, the energy consumption was recorded with the electrical energy monitor by the wastewater treatment utility, and the carbon emission changes were calculated using the emission intensity of the power utility. The results show that after the replacement, both energy usage and energy costs were significantly reduced, with the energy usage having decreased by 70% and its cost by 47%. Additionally, carbon-equivalent emission from electricity importation dropped by 64%, with an effect on the overall carbon emissions (i.e., including all other contributions from the process) decreasing from 3.8% to 1.5%.

Diurnal variations of the energy intensity and associated greenhouse gas emissions for activated sludge processes.

A model was developed for a water resources recovery facility (WRRF) activated sludge process (ASP) in Modified Ludzack-Ettinger (MLE) configuration. Amplification of air requirements and its associated energy consumptions were observed as a result of concurrent circadian variations in ASP influent flow and carbonaceous/nitrogenous constituent concentrations. The indirect carbon emissions associated with the ASP aeration were further amplified due to the simultaneous variations in carbon emissions intensity (kgCO2,eq(kWh)-1) and electricity consumption (kWh). The ratio of peak to minimum increased to 3.4 (for flow), 4.2 (for air flow and energy consumption), and 5.2 (for indirect CO2,eq emission), which is indicative of strong amplification. Similarly, the energy costs for ASP aeration were further increased due to the concurrency of peak energy consumptions and power demands with time of use peak electricity rates. A comparison between the results of the equilibrium model and observed data from the benchmark WRRF demonstrated under- and over-aeration attributed to the circadian variation in air requirements and limitations associated with the aeration system specification and design.

Accelerating Innovation that Enhances Resource Recovery in the Wastewater Sector: Advancing a National Testbed Network.

This Feature examines significant challenges and opportunities to spur innovation and accelerate adoption of reliable technologies that enhance integrated resource recovery in the wastewater sector through the creation of a national testbed network. The network is a virtual entity that connects appropriate physical testing facilities, and other components needed for a testbed network, with researchers, investors, technology providers, utilities, regulators, and other stakeholders to accelerate the adoption of innovative technologies and processes that are needed for the water resource recovery facility of the future. Here we summarize and extract key issues and developments, to provide a strategy for the wastewater sector to accelerate a path forward that leads to new sustainable water infrastructures.

Fate and Toxicity of Zinc Oxide Nanomaterial in Municipal Wastewaters.

The production of zinc nanomaterial has increased significantly over the past several years and, as a result, nanoparticles have navigated their way into wastewater streams. The transportation and toxicity of zinc nanomaterial within the wastewater treatment processes is not well known. In this study, the zinc nanomaterial and its fate were characterized in an activated sludge treatment process. The tests performed included batch studies to evaluate abiotic and biotic removal, toxicity studies to evaluate inhibition to coliform and nitrifying bacteria, and bioreactor studies to evaluate impact on operating parameters. Stock solutions of zinc nanomaterial varied in size from 50 to 500 nm, but when added to an activated sludge solution, the nanoparticles agglomerated to larger sizes such that more than 60% of the zinc nanomaterial settled out of solution. However, when ionic zinc was added to activated sludge, more than 60% of the ionic zinc remained in suspension. It is likely that the ionic strength of the wastewater influenced the aggregation of the nanomaterial. Differences in the extent of removal between ionic and nano zinc species indicate that the mechanisms governing their removal are different. Toxicity analysis showed that zinc nanomaterial did not inhibit growth of coliform and ammonia oxidizing bacteria. However, ionic zinc inhibited the growth of both the coliform and ammonia oxidizing bacteria. Bioreactors were set up using activated sludge that was collected from a local treatment plant operating only in carbon oxidation mode. The treatment plant was operated at an SRT of 1.2 days and an MLSS of 650 mg/L. Several key parameters (COD, MLSS, pH) in the bioreactors were monitored through a 7-day incubation period, but showed no significant changes due to the addition of nano or ionic zinc. It is possible that the toxicity of zinc nanomaterial was not observed in these experiments because the nanomaterial agglomerated and settled out of solution.

Reverse flexing as a physical/mechanical treatment to mitigate fouling of fine bubble diffusers.

Achieving energy neutrality has shifted focus towards aeration system optimization, due to the high energy consumption of aeration processes in modern advanced wastewater treatment plants. A study on fine bubble diffuser fouling and mitigation, quantified by dynamic wet pressure (DWP), oxygen transfer efficiency and alpha was carried out in Blue Plains, Washington, DC. Four polyurethane fine bubble diffusers were installed in a pilot reactor column fed with high rate activated sludge from a full scale system. A mechanical cleaning method, reverse flexing (RF), was used to treat two diffusers (RF1, RF2), while two diffusers were kept as a control (i.e., no reverse flexing). There was a 45% increase in DWP of the control diffuser after 17 months of operation, an indication of fouling. RF treated diffusers (RF1 and RF2) did not show significant increase in DWP, and in comparison to the control diffuser prevented about 35% increase in DWP. Hence, reverse flexing potentially saves blower energy, by reducing the pressure burden on the air blower which increases blower energy requirement. However, no significant impact of the RF treatment in preventing a decrease in alpha-fouling (αF) of the fine pore diffusers, over time in operation was observed.

Identification of Preferential Paths of Fossil Carbon within Water Resource Recovery Facilities via Radiocarbon Analysis.

The Intergovernmental Panel on Climate Change (IPCC) reported that all carbon dioxide (CO2) emissions generated by water resource recovery facilities (WRRFs) during treatment are modern, based on available literature. Therefore, such emissions were omitted from IPCC's greenhouse gas (GHG) accounting procedures. However, a fraction of wastewater's carbon is fossil in origin. We hypothesized that since the fossil carbon entering municipal WRRFs is mostly from soaps and detergents as dissolved organic matter, its fate can be selectively determined during the universally applied separation treatment processes. Analyzing radiocarbon at different treatment points within municipal WRRFs, we verified that the fossil content could amount to 28% in primary influent and showed varying distribution leaving different unit operations. We recorded the highest proportion of fossil carbon leaving the secondary treatment as off-gas and as solid sludge (averaged 2.08 kg fossil-CO2-emission-potential m-3 wastewater treated). By including fossil CO2, total GHG emission in municipal WRRFs increased 13%, and 23% if an on-site energy recovery system exists although much of the postdigestion fossil carbon remained in biosolids rather than in biogas, offering yet another carbon sequestration opportunity during biosolids handling. In comparison, fossil carbon contribution to GHG emission can span from negligible to substantial in different types of industrial WRRFs. With such a considerable impact, CO2 should be analyzed for each WRRF and not omitted from GHG accounting.