The use of a fitted parameter watershed model to address water quantity and quality management issues requires that it be calibrated under a wide range of hydrologic conditions. However, rarely does model calibration result in a unique parameter set. Parameter nonuniqueness can lead to predictive nonuniqueness. The extent of model predictive uncertainty should be investigated if management decisions are to be based on model projections. Using models built for four neighboring watersheds in the Neuse River Basin of North Carolina, the application of the automated parameter optimization software PEST in conjunction with the Hydrologic Simulation Program Fortran (HSPF) is demonstrated. Parameter nonuniqueness is illustrated, and a method is presented for calculating many different sets of parameters, all of which acceptably calibrate a watershed model. A regularization methodology is discussed in which models for similar watersheds can be calibrated simultaneously. Using this method, parameter differences between watershed models can be minimized while maintaining fit between model outputs and field observations. In recognition of the fact that parameter nonuniqueness and predictive uncertainty are inherent to the modeling process, PEST's nonlinear predictive analysis functionality is then used to explore the extent of model predictive uncertainty.

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations—where observing outcomes is difficult—versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test endpoints, duration, and study conditions—including ENM test concentrations—that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.

No abstract

Cyanobacterial harmful algal blooms (cyanoHAB) cause extensive problems in lakes worldwide, including human and ecological health risks, anoxia and fish kills, and taste and odor problems. CyanoHABs are a particular concern in both recreational waters and drinking source waters because of their dense biomass and the risk of exposure to toxins. Successful cyanoHAB assessment using satellites may provide an indicator for human and ecological health protection, In this study, methods were developed to assess the utility of satellite technology for detecting cyanoHAB frequency of occurrence at locations of potential management interest. The European Space Agency's MEdium Resolution Imaging Spectrometer (MERIS) was evaluated to prepare for the equivalent series of Sentine1-3 Ocean and Land Colour Imagers (OLCI) launched in 2016 as part of the Copernicus program. Based on the 2012 National Lakes Assessment site evaluation guidelines and National Hydrography Dataset, the continental United States contains 275,897 lakes and reservoirs >1 hectare in area. Results from this study show that 5.6 % of waterbodies were resolvable by satellites with 300 m single-pixel resolution and 0.7 % of waterbodies were resolvable when a three by three pixel (3×3-pixel) array was applied based on minimum Euclidian distance from shore. Satellite data were spatially joined to U.S. public water surface intake (PWSI) locations, where single-pixel resolution resolved 57% of the PWSI locations and a 3×3-pixel array resolved 33% of the PWSI locations. Recreational and drinking water sources in Florida and Ohio were ranked from 2008 through 2011 by cyanoHAB frequency above the World Health Organization's (WHO) high threshold for risk of 100,000 cells mL. The ranking identified waterbodies with values above the WHO high threshold, where Lake Apopka, FL (99.1 %) and Grand Lake St. Marys, OH (83 %) had the highest observed bloom frequencies per region. The method presented here may indicate locations with high exposure to cyanoHABs and therefore can be used to assist in prioritizing management resources and actions for recreational and drinking water sources.

To further understanding of the environmental implications of rainwater harvesting and its water savings potential relative to conventional U.S. water delivery infrastructure, we present a method to perform life cycle assessment of domestic rainwater harvesting (DRWH) and agricultural rainwater harvesting (ARWH) systems. We also summarize the design aspects of DRWH and ARWH systems adapted to the Back Creek watershed, Virginia. The baseline design reveals that the pump and pumping electricity are the main components of DRWH and ARWH impacts. For nonpotable uses, the minimal design of DRWH (with shortened distribution distance and no pump) outperforms municipal drinking water in all environmental impact categories except ecotoxicity. The minimal design of ARWH outperforms well water in all impact categories. In terms of watershed sustainability, the two minimal designs reduced environmental impacts, from 58% to 78% energy use and 67% to 88% human health criteria pollutants, as well as avoiding up to 20% blue water (surface/groundwater) losses, compared to municipal drinking water and well water. We address potential environmental and human health impacts of urban and rural RWH systems in the region. The Building for Environmental and Economic Sustainability (BEES) model-based life cycle inventory data were used for this study.

Chimeric antigen receptor (CAR)–engineered T‐cell therapy is becoming one of the most promising approaches in the treatment of cancer. On June 28, 2018, the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kymriah for pediatric and young adult patients up to 25 years of age with B‐cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse after transplant, or in second or later relapse and for adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) after two or more lines of systemic therapy. Kymriah became one of the first European Union–approved CAR T therapies. The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy that involves reprogramming the patient's own T cells to identify and eliminate CD19‐expressing cells. This is achieved by addition of a transgene encoding a CAR. The benefit of Kymriah was its ability to achieve remission with a significant duration in patients with ALL and an objective response with a significant duration in patients with DLBCL. The most common hematological toxicity was cytopenia in both patients with ALL and those with DLBCL. Nonhematological side effects in patients with ALL were cytokine release syndrome (CRS), infections, secondary hypogammaglobulinemia due to B‐cell aplasia, pyrexia, and decreased appetite. The most common nonhematological side effects in patients with DLBCL were CRS, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. Kymriah also received an orphan designation on April 29, 2014, following a positive recommendation by the Committee for Orphan Medicinal Products (COMP). Maintenance of the orphan designation was recommended at the time of marketing authorization as the COMP considered the product was of significant benefit for patients with both conditions. Implications for Practice Chimeric antigen receptor (CAR)–engineered T‐cell therapy is becoming the most promising approach in cancer treatment, involving reprogramming the patient's own T cells with a CAR‐encoding transgene to identify and eliminate cancer‐specific surface antigen–expressing cells. On June 28, 2018, Kymriah became one of the first EMA approved CAR T therapies. CAR T technology seems highly promising for diseases with single genetic/protein alterations; however, for more complex diseases there will be challenges to target clonal variability within the tumor type or clonal evolution during disease progression. Products with a lesser toxicity profile or more risk‐minimization tools are also anticipated.

Lung tissue explants from mid-trimester human abortuses were maintained for 8 days in organ culture in medium with or without serum. Before the start of culture the cells lining the pre-alveolar ducts were undifferentiated and contained no lamellar bodies, the intracellular organelle that contains surfactant. After 4 days in organ culture, the epithelium lining the pre-alveolar ducts was composed of differentiated type II cells containing numerous lamellar bodies. During the 8-day culture period there was increased incorporation of [3H]choline into phosphatidylcholine and disaturated phosphatidylcholine. In addition, the specific activity of phosphatidate phosphohydrolase, a regulatory enzyme in lung phospholipid synthesis, increased 4-fold during the culture period. Lamellar bodies isolated by differential centrifugation from explants maintained in culture for 7 days had the characteristic ultrastructure described for this organelle. Lamellar bodies were isolated from explants which had been incubated with [14C]glycerol. When the glycerophospholipid composition of lamellar bodies was analyzed it was found that the majority of the radiolabeled glycerol (74%) was incorporated into phosphatidylcholine and into the anionic phospholipids, phosphatidylglycerol (5%) and phosphatidylinositol (6%). Thus, human fetal lung explants maintained in organ culture contain differentiated type II cells which synthesize surfactant characteristic of human fetal lung at 36 to 38 weeks of gestation.

As the use of engineered nanomaterials becomes more prevalent, the likelihood of unintended exposure to these materials also increases. Given the current scarcity of experimental data regarding fate, transport, and bioavailability, determining potential environmental exposure to these materials requires an in depth analysis of modeling techniques that can be used in both the near- and long-term. Here, we provide a critical review of traditional and emerging exposure modeling approaches to highlight the challenges that scientists and decision-makers face when developing environmental exposure and risk assessments for nanomaterials. We find that accounting for nanospecific properties, overcoming data gaps, realizing model limitations, and handling uncertainty are key to developing informative and reliable environmental exposure and risk assessments for engineered nanomaterials. We find methods suited to recognizing and addressing significant uncertainty to be most appropriate for near-term environmental exposure modeling, given the current state of information and the current insufficiency of established deterministic models to address environmental exposure to engineered nanomaterials.