bluuebunny/crossref_metadata_2025 huggingface dataset:
Thy1‐YFP‐H Mice and the Parallel Rod Floor Test to Evaluate Short‐ and Long‐Term Progression of Traumatic Brain Injury
Authors: Richter Monique , Negro‐Demontel María Luciana , Blanco‐Ocampo Daniela , Taranto Eliseo , Lago Natalia , Peluffo Hugo
Published: February 2018

Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long‐term follow‐up is needed. We have used the Thy1‐YFP‐H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury. This approach reveals short‐ and long‐term progressive changes, including compromised biphasic motor function up to 85 days post‐lesion, which correlates with neuronal atrophy, dendrite and spine loss, and long‐term axonal pathology evidenced by axon spheroids and fragmentation. Here we present methods for inducing a controlled cortical injury in the Thy1‐YFP‐H transgenic mouse line and for evaluating the resulting deficits in the parallel rod floor test. This technique constitutes a new, unbiased, and robust method for the evaluation of motor and behavioral alterations after TBI. © 2018 by John Wiley & Sons, Inc.
Intravital Imaging of Neuroimmune Interactions Through a Thinned Skull
Authors: Manglani Monica , McGavern Dorian B.
Published: February 2018

Innate and adaptive immune interactions within the central nervous system (CNS) and surrounding meninges contribute significantly to neural homeostasis as well as a variety of different neurological disorders. Two‐photon laser scanning microscopy is a deep tissue imaging technique that provides a means to image immune cell dynamics and interactions in the living CNS with high spatial and temporal resolution. Optical access to the brain and meninges can be achieved through the creation of thinned skull windows, which can be made without inducing damage and inflammation in the underlying tissue. This protocol provides guidance on how to create a thinned skull window without causing CNS injury. We also describe a highly reproducible method to induce a mild traumatic brain injury using the thinned skull approach. © 2018 by John Wiley & Sons, Inc.
Growth and Laboratory Maintenance of Paenibacillus larvae
Authors: Mahdi Osama S. , Fisher Nathan A
Published: February 2018

Paenibacillus larvae is a Gram‐positive, spore‐forming bacterium and the causative agent of American foulbrood disease (AFB), a highly contagious, fatal disease affecting managed honeybee (Apis mellifera) colonies. As the etiological agent of American foulbrood disease, P. larvae is the most economically significant bacterial pathogen infecting honeybees. This unit includes protocols for the in vitro growth and laboratory maintenance of P. larvae. © 2018 by John Wiley & Sons, Inc.
BioID: A Screen for Protein‐Protein Interactions
Authors: Roux Kyle J. , Kim Dae In , Burke Brian , May Danielle G.
Published: February 2018

BioID is a unique method to screen for physiologically relevant protein interactions that occur in living cells. This technique harnesses a promiscuous biotin ligase to biotinylate proteins based on proximity. The ligase is fused to a protein of interest and expressed in cells, where it biotinylates proximal endogenous proteins. Because it is a rare protein modification in nature, biotinylation of these endogenous proteins by BioID fusion proteins enables their selective isolation and identification with standard biotin‐affinity capture. Proteins identified by BioID are candidate interactors for the protein of interest. BioID can be applied to insoluble proteins, can identify weak and/or transient interactions, and is amenable to temporal regulation. Initially applied to mammalian cells, BioID has potential application in a variety of cell types from diverse species. © 2018 by John Wiley & Sons, Inc.
CYP2D6 and Endoxifen in Tamoxifen Therapy: A Tribute to David A. Flockhart
Authors: Skaar Todd C. , Desta Zeruesenay
Published: February 2018

This issue of Clinical Pharmacology & Therapeutics (CPT) includes the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for using CYP2D6 genotyping to guide tamoxifen therapy for breast cancer patients. CYP2D6 metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with reduced CYP2D6 activity have reduced circulating endoxifen concentrations. In this associated commentary, we recognize and honor the late Dr. David Flockhart, who began the research and made early fundamental discoveries on tamoxifen that have now resulted in this guideline.
Considerations for Developing Targeted Therapies in Low‐Frequency Molecular Subsets of a Disease
Authors: Schuck Robert N. , Woodcock Janet , Zineh Issam , Stein Peter , Jarow Jonathan , Temple Robert , Permutt Thomas , LaVange Lisa , Beaver Julia A. , Charlab Rosane , Blumenthal Gideon M. , Dorff Sarah E. , Leptak Christopher , Lemery Steven , Rogers Hobart , Chowdhury Badrul , Litwack E. David , Pacanowski Michael
Published: February 2018

Advances in our understanding of the molecular underpinnings of disease have spurred the development of targeted therapies and the use of precision medicine approaches in patient care. While targeted therapies have improved our capability to provide effective treatments to patients, they also present additional challenges to drug development and benefit–risk assessment such as identifying the subset(s) of patients likely to respond to the drug, assessing heterogeneity in response across molecular subsets of a disease, and developing diagnostic tests to identify patients for treatment. These challenges are particularly difficult to address when targeted therapies are developed to treat diseases with multiple molecular subtypes that occur at low frequencies. To help address these challenges, the US Food and Drug Administration recently published a draft guidance entitled “Developing Targeted Therapies in Low‐Frequency Molecular Subsets of a Disease.” Here we provide additional information on specific aspects of targeted therapy development in diseases with low‐frequency molecular subsets.
Use of Human Embryoid Bodies for Teratology
Authors: Flamier Anthony , Singh Supriya , Rasmussen Theodore P.
Published: February 2018

Human birth defects are relatively common and can be caused by exposure to environmental teratogens or to pharmaceuticals with teratogenic activities. Human embryonic stem cells (hESCs), by virtue of their pluripotent nature, provide an excellent cellular platform for teratogen detection and risk assessment. This unit describes detailed protocols for the preparation and validation of highly pluripotent hESCs, the production of large quantities of aggregated multicellular spheroids composed of hESCs, and these spheroids’ differentiation into embryoid bodies (EBs). EBs contain a variety of cells of endodermal, ectodermal, and mesodermal origin and can be subjected to compound exposure in vitro. Hence, they are useful for the detection of chemicals with teratogenic activities. Beyond describing protocols to assemble and culture EBs, this unit details methods to exploit the EB system for teratological assessment. In addition, strategies to distinguish compounds with bona fide teratogenic activity versus simple toxicity are discussed. © 2018 by John Wiley & Sons, Inc.
A Real‐Time Image‐Based Approach to Distinguish and Discriminate Apoptosis from Necrosis
Authors: Lekshmi Asha , Varadarajan Shankara Narayanan , Lupitha Santhik Subhasingh , Nair Mydhily , Chandrasekharan Aneesh , Santhoshkumar T.R.
Published: February 2018

Recent cell biology studies reveal that a cell can die through multiple pathways via distinct signaling mechanisms. Among these, apoptosis and necrosis are two distinct cell death pathways, and their detection and discrimination is vital in the drug discovery process and in understanding diverse biological processes. Although sensitive assays for apoptosis and necrosis are available, it is extremely difficult to adapt any of these methods to discriminate apoptosis‐inducing stimuli from necrosis‐inducing stimuli because of the acquisition of secondary necrosis by apoptotic cells when they are not phagocytosed. Essentially, any assay for discriminating apoptosis and necrosis needs to be carried out in real‐time kinetic mode. Caspase 3 or 7 activation is observed in the majority of apoptotic cell death. Similarly, the absence of caspase 3/7 activation and cell membrane leakage are the two prominent indicators for necrotic cell death or necroptosis. The programmed form of necrosis, called pyroptosis, is also accompanied by membrane leakage and most often associated with activation of specific caspases such as caspase 1, 4, or 11, but not through caspase 3/7 activation. Here, a robust and sensitive real‐time method is described to distinguish and discriminate apoptosis from necrosis. The assay utilizes stable integration of a genetically encoded fluorescence resonance energy transfer (FRET) probe for caspase 3/7 activation and the mitochondrion‐targeted DsRed to identify necrotic cells. Caspase activation is determined by cleavage of the FRET probe; loss of soluble FRET probe with retention of mitochondrial red fluorescence indicates necrosis. This unit describes an important protocol for the generation of sensor cells expressing both probes, followed by detailed analysis of apoptosis and necrosis by microscopy imaging, confocal imaging, high‐throughput imaging, and flow cytometry. © 2018 by John Wiley & Sons, Inc.
Preparation of Human Primary Colon Tissue‐Derived Organoid Using Air Liquid Interface Culture
Authors: Usui Tatsuya , Sakurai Masashi , Umata Koji , Yamawaki Hideyuki , Ohama Takashi , Sato Koichi
Published: February 2018

In vitro analysis of intestinal epithelium has been hindered by a lack of suitable culture systems useful for gastrointestinal research. To overcome the problem, an air liquid interface (ALI) method using a collagen gel was established to culture three‐dimensional primary cells containing both primary epithelial and mesenchymal components from mouse gastrointestinal tissues. ALI organoids accurately recapitulate organ structures, multilineage differentiation, and physiology. Since ALI organoids from human tissues have not been produced, we modified the previous protocol for mouse ALI organoid culture to establish the culture system of ALI organoids from normal and tumor colorectal tissues of human patients. The current unit presents a protocol for preparation of the ALI organoid culture from normal and tumor colorectal tissues of human patients. ALI organoid culture from human tissues might be useful for examining not only resistance to chemotherapy in a tumor microenvironment but also toxic effects on organoids. © 2018 by John Wiley & Sons, Inc.
Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis
Authors: Kaplan Barbara L. F.
Published: February 2018

Cannabinoid compounds refer to a group of more than 60 plant‐derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one's ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE. © 2018 by John Wiley & Sons, Inc.
Development of an In Vitro Method to Estimate the Sensitization Induction Level of Contact Allergens
Authors: Galbiati Valentina , Gibbs Sue , Roggen Erwin , Corsini Emanuela
Published: February 2018

Recently, an in vitro procedure, which combines the epidermal equivalent potency assay with assessment of IL‐18 to provide a single test for identification and classification of skin sensitizers, was developed and validated. This unit will describe a simple in vitro method for estimation of the expected sensitization induction level interpolating in vitro EC50 and IL‐18 SI2 values to predict LLNA EC3 and/or human NOEL from standards curves generated using reference contact allergens, based on the use of Reconstituted human Epidermis (RhE).© 2018 by John Wiley & Sons, Inc.
2‐(N‐Methylbenzyl)pyridine: A Potential Liquid Organic Hydrogen Carrier with Fast H2 Release and Stable Activity in Consecutive Cycles
Authors: Oh Jinho , Jeong Kwanyong , Kim Tae Wan , Kwon Hyunguk , Han Jeong Woo , Park Ji Hoon , Suh Young‐Woong
Published: February 2018

Invited for this month's cover is the group of Prof. Young‐Woong Suh at Hanyang University, in collaboration with Dr. Ji Hoon Park at Korea Research Institute of Chemical Technology and Prof. Jeong Woo Han at Pohang at University of Science and Technology. The Cover image is a representation of the H2 economy based on production, storage, and utilization for fuel cell electric vehicles, using our developed liquid organic hydrogen carrier (LOHC) material 2‐(N‐methylbenzyl)pyridine. The Communication itself is available at 10.1002/cssc.201702256.
Fine root responses to temporal nutrient heterogeneity and competition in seedlings of two tree species with different rooting strategies
Authors: Wang Peng , Shu Meng , Mou Pu , Weiner Jacob
Published: February 2018

There is little direct evidence for effects of soil heterogeneity and root plasticity on the competitive interactions among plants. In this study, we experimentally examined the impacts of temporal nutrient heterogeneity on root growth and interactions between two plant species with very different rooting strategies:Liquidambar styraciflua(sweet gum), which shows high root plasticity in response to soil nutrient heterogeneity, andPinus taeda(loblolly pine), a species with less plastic roots. Seedlings of the two species were grown in sandboxes in inter‐ and intraspecific combinations. Nutrients were applied in a patch either in a stable (slow‐release) or in a variable (pulse) manner. Plant aboveground biomass, fine root mass, root allocation between nutrient patch and outside the patch, and root vertical distribution were measured.L. styracifluagrew more aboveground (40% and 27% in stable and variable nutrient treatment, respectively) and fine roots (41% and 8% in stable and variable nutrient treatment, respectively) when competing withP. taedathan when competing with a conspecific individual, but the growth ofP. taedawas not changed by competition fromL. styraciflua. Temporal variation in patch nutrient level had little effect on the species’ competitive interactions. The more flexibleL. styracifluachanged its vertical distribution of fine roots in response to competition fromP. taeda, growing more roots in deeper soil layers compared to its roots in conspecific competition, leading to niche differentiation between the species, while the fine root distribution ofP. taedaremained unchanged across all treatments.Synthesis.L. styracifluashowed greater flexibility in root growth by changing its root vertical distribution and occupying space of not occupied byP. taeda. This flexibility gaveL. styracifluaan advantage in interspecific competition.
Persistence and space preemption explain species‐specific founder effects on the organization of marine sessile communities
Authors: Vieira Edson A. , Flores Augusto A. V. , Dias Gustavo M.
Published: February 2018

Community assembly may not follow predictable successional stages, with a large fraction of the species pool constituted by potential pioneering species and successful founders defined through lottery. In such systems, priority effects may be relevant in the determination of trajectories of developing communities and hence diversity and assemblage structure at later advanced states. In order to assess how different founder species may trigger variable community trajectories and structures, we conducted an experimental study using subtidal sessile assemblages as model. We manipulated the identity of functionally different founders and initial colony size (a proxy of the time lag before the arrival of later species), and followed trajectories. We did not observe any effects of colony size on response variables, suggesting that priority effects take place even when the time lag between the establishment of pioneering species and late colonizers is very short. Late community structure at experimental panels that started either with the colonial ascidian Botrylloides nigrum, or the arborescent bryozoan Bugula neritina, was similar to control panels allowed natural assembling. In spite of high potential for fast space domination, and hence negative priority effects, B. nigrum suffered high mortality and did not persist throughout succession. Bugula neritina provided complex physical microhabitats through conspecific clustering that have enhanced larval settlement of late species arrivals, but no apparent facilitation was observed. Differently, panels founded by the encrusting bryozoan Schizoporella errata led to different and less diverse communities compared to naturally assembled panels, evidencing strong negative priority effects through higher persistence and space preemption. Schizoporella errata founder colonies inhibited further conspecific settlement, which may greatly relax intraspecific competition, allowing resource allocation to colony growth and space domination, thus reducing the chances for the establishment of other species.
What drives biological nitrogen fixation in high arctic tundra: Moisture or temperature?
Authors: Rousk Kathrin , Sorensen Pernille Laerkedal , Michelsen Anders
Published: February 2018

Biological nitrogen (N2) fixation is one of the main sources of available N for pristine ecosystems such as subarctic and arctic tundra. Although this has been acknowledged more than a decade ago, few attempts have been undertaken to identify the foremost driver of N2 fixation in the high Arctic. Here, we report results from in situ measurements of N2 fixation throughout the main growing period (June–August) in high arctic tundra, Greenland, in climate change treatments, shading and warming, and control. Nitrogen fixation was also measured in cores that received additional water prior to the measurements. The climate change field treatments did not lead to significant changes in any measured parameters; however, N2 fixation was promoted by adding water, and moisture was the most important factor influencing N2 fixation in all climate change field treatments. Maximum N2 fixation rates were measured below 14°C soil temperature, which is much lower than the theoretical and previously reported temperature optimum for the nitrogenase enzyme. Diazotroph (N2 fixing bacteria) communities are adapted to low temperatures in high arctic settings, and increased temperature in a future climate may lead to decreased N2 fixation rates, or to a shift in diazotroph communities.
Influence of different discourses on the outcomes of development policies and projects: Insights from water project implementation in Nepal
Authors: Haapala Juho , Keskinen Marko
Published: February 2018

This study develops a systematic, participatory research method to study the impacts of different discourses on the outcomes of development policies and projects. The method visualizes relationships between key project discourses, enabling comparisons to be made between stated and actual discourses, and recognition of mutual synergies or inconsistencies among the discourses. Case study analysis of a rural water resources management project in Nepal demonstrates the ways in which individual responses from project specialists, combined together, lead to distinct hierarchical groups and clusters of discourses that reflect the day‐to‐day ways in which policies and projects are implemented. The paper discusses the ways in which project and organizational management could utilize the analysis in project planning, team formation, monitoring and supervision to meet external policy requirements, fit with local realities, and improve policy and project outcomes.
Entrapment of distilled palmarosa (cymbopogon martinii) wastes in alginate beads for adsorptive removal of methylene blue from aqueous solution
Authors: Saha Ajoy , Tripathy Vandana , Basak B. B. , Kumar Jitendra
Published: February 2018

This study described a preparation of a low‐cost adsorbent by entrapment of palmarosa distillation wastes into alginate as supporting matrix and use of it for methylene blue (MB) dye removal from aqueous solution. Fourier transform infrared spectroscopy (FTIR) data of adsorbent confirms the entrapment for formation of composite beads. The effects of adsorption parameters (adsorbent dose, temperature, initial dye concentration, and pH) were investigated. Time to reach the equilibrium was dependent on dye concentration and it was 120 min for lower concentration and 240 min for higher concentration. The analysis of the kinetic data by pseudo‐first‐order and pseudo‐second‐order models displayed that MB adsorption followed pseudo‐second‐order model. The equilibrium data of MB adsorption were described by applying the Langmuir, Freundlich, and Temkin models. The observations from adsorption isotherms indicated that Langmuir model is the best fitted model and the maximum adsorption capacity (at the optimum pH 9.0) improved from 5.71 to 6.45 mg/g as the temperature increased from 298 to 328 K. The thermodynamic studies demonstrated that MB adsorption on to the adsorbent was spontaneous, feasible, and endothermic. Low desorption of the dyes from the adsorbent indicates that the dyes might have been chemisorbed on to the adsorbent surface. A single‐stage batch adsorber was designed and quantity of adsorbent required for treating 1–10 L of stained water was determined based on the Langmuir isotherm model equation. Results indicate that the composite bead could be an alternative for relatively costly adsorbents used for remediation of MB dye bearing industrial effluents. © 2018 American Institute of Chemical Engineers Environ Prog, 37: 1901–1907, 2018
Comparing apples and oranges and pears and kumquats: The misuse of index systems for processing histopathology data in fish toxicological bioassays
Authors: Wolf Jeffrey C.
Published: February 2018

Histopathology index systems involve the application of weighted scores to various diagnostic findings for the purpose of calculating overall organ and/or whole-animal health measurements. Such systems were originally developed as tools for monitoring the general health of fish populations. More recently, index systems have been applied to hypothesis-based toxicological studies, the goal of which is to investigate whether a cause-and-effect relationship exists between exposure to a particular test substance or environmental contaminant and morphologic effects in fish tissues. However, the application of index systems in that context is problematic for various reasons: a dependency on untested assumptions of toxicological importance for different types of histopathologic findings; organ scores that combine mechanistically unrelated and potentially contradictory diagnoses; calculations that include excessive numbers of findings, some of which may be incidental to the study outcome; failure to incorporate additional relevant results into the data interpretation, such as clinical observations, macroscopic findings, organ/body weights, clinical pathology data, and the results of hormonal or other biochemical assays; the inappropriate mathematical manipulation of ordinal categorical data (e.g., severity scores and “importance factors”); and a tendency of these systems to amplify, mask, and divert attention from methodological weaknesses and inaccurate diagnoses. The purpose of the present article is to demonstrate why the use of index systems is a misguided approach for handling histopathology data in studies of potential fish toxicants. Environ Toxicol Chem 2018;37:1688–1695. © 2018 SETAC
Estimating incident ultraviolet radiation exposure in the northern Gulf of Mexico during the Deepwater Horizon oil spill
Authors: Nielsen Kristin M. , Lay Claire R. , Alloy Matthew M. , Gielazyn Michel L. , Morris Jeffrey M. , Forth Heather P. , Takeshita Ryan , Travers Constance L. , Oris James T. , Roberts Aaron P.
Published: February 2018

Millions of barrels of oil were released into the Gulf of Mexico following the 2010 explosion of the Deepwater Horizon oil rig. Polycyclic aromatic hydrocarbons (PAHs) are toxic components of crude oil, which may become more toxic in the presence of ultraviolet (UV) radiation, a phenomenon known as photo-induced toxicity. The Deepwater Horizon spill impacted offshore and estuarine sites, where biota may be co-exposed to UV and PAHs. Penetration of UV into the water column is affected by site-specific factors. Therefore, measurements and/or estimations of UV are necessary when one is assessing the risk to biota posed by photo-induced toxicity. We describe how estimates of incident UV were determined for the area impacted by the Deepwater Horizon oil spill, using monitoring data from radiometers near the spill, in conjunction with reference spectra characterizing the composition of solar radiation. Furthermore, we provide UV attenuation coefficients for both near- and offshore sites in the Gulf of Mexico. These estimates are specific to the time and location of the spill, and fall within the range of intensities utilized during photo-induced toxicity tests performed in support of the Deepwater Horizon Natural Resource Damage Assessment (NRDA). These data further validate the methodologies and findings of phototoxicity tests included in the Deepwater Horizon NRDA, while underscoring the importance of considering UV exposure when assessing possible risks following oil spills. Environ Toxicol Chem 2018;37:1679–1687. © 2018 SETAC
Enhanced Flocculation of Oil Sands Mature Fine Tailings Using Hydrophobically Modified Polyacrylamide Copolymers
Authors: Hripko Rhys , Vajihinejad Vahid , LopesMotta Fernanda , Soares João B. P.
Published: February 2018

Hydrophobically modified acrylamide copolymers dewater oil sands tailings more effectively than anionic polyacrylamide, but the root causes for this enhanced performance have not been investigated systematically. Polyacrylamide‐poly(ethylene oxide methyl ether methacrylate) copolymers with different comonomer compositions, hydrophobic chain lengths, and molecular weights to map out these effects systematically are synthetized. Through a statistical design of experiments, it is found out that all three variables above significantly affected flocculation performance and that certain combinations achieve optimal results. The effect of centrifugation on the flocculation and dewatering performance of these polymers is also investigated.
Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial
Authors: Foster Graham R. , Agarwal Kosh , Cramp Matthew E. , Moreea Sulleman , Barclay Stephen , Collier Jane , Brown Ashley S. , Ryder Stephen D. , Ustianowski Andrew , Forton Daniel M. , Fox Ray , Gordon Fiona , Rosenberg William M. , Mutimer David J. , Du Jiejun , Gilbert Christopher L. , Asante‐Appiah Ernest , Wahl Janice , Robertson Michael N. , Barr Eliav , Haber Barbara
Published: February 2018

Many direct‐acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT) 3 infection and cirrhosis. The C‐ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open‐label study. Treatment‐naive participants received EBR/GZR + SOF + RBV for 8 weeks or EBR/GZR + SOF for 12 weeks, and peginterferon/RBV treatment‐experienced participants received EBR/GZR + SOF ± RBV for 12 weeks or EBR/GZR + SOF for 16 weeks. The primary endpoint was HCV RNA <15 IU/mL 12 weeks after the end of treatment (sustained virologic response at 12 weeks [SVR12]). Among treatment‐naive participants, SVR12 was 91% (21/23) in those treated with RBV for 8 weeks and 96% (23/24) in those treated for 12 weeks. Among treatment‐experienced participants, SVR12 was 94% (17/18) and 100% (17/17) in the 12‐week arm, with and without RBV, respectively, and 94% (17/18) in the 16‐week arm. Five participants failed to achieve SVR: 2 relapsed (both in the 8‐week arm), 1 discontinued due to vomiting/cellulitis (16‐week arm), and 2 discontinued (consent withdrawn/lost to follow‐up). SVR12 was not affected by the presence of resistance‐associated substitutions (RASs). There was no consistent change in insulin resistance, and 5 participants reported serious adverse events (pneumonia, chest pain, opiate overdose, cellulitis, decreased creatinine). High efficacy was demonstrated in participants with HCV GT3 infection and cirrhosis. Treatment beyond 12 weeks was not required, and efficacy was maintained regardless of baseline RASs. Conclusion: Data from this study support the use of EBR/GZR plus SOF for 12 weeks without RBV for treatment‐naive and peginterferon/RBV–experienced people with GT3 infection and cirrhosis (ClinicalTrials.gov NCT02601573). (Hepatology 2018;67:2113‐2126)
Engaging Farmers in a Research Project. Lessons Learned from Implementing the Community of Practice Concept in Innovation Platforms in Irrigated Schemes in Tunisia, Mozambique and Ethiopia
Authors: Dolinska Aleksandra , Oates Naomi , Ludi Eva , Habtu Solomon , Rougier Jean‐Emmanuel , Sanchez‐Reparaz Maite , Mosello Beatrice , Yazew Eyasu , Kifle Muluberhan , Fissehaye Degol , Aregay Gebremeskel , Tamele Higino Fabiao , Barberá Gonzalo G. , d'Aquino Patrick
Published: February 2018

The role of smallholder farmers in multi‐stakeholder innovation platforms and thus in the innovation process that these platforms facilitate is typically limited. The EAU4Food project, aimed at increasing food production in irrigation schemes in Africa through improved farming strategies, used a platform design inspired by the community of practice (CoP) concept, which opened up space for farmers' interactive learning and enabled their active participation in the innovation process. In this article we present examples of how this approach has been implemented in Ethiopia, Mozambique and Tunisia. We analyse the level of farmers' participation that was achieved at different stages of the implementation process, namely: deciding how to set up the CoP, identifying innovation needs and conducting the experiment. Among different strategies deployed by EAU4Food researchers, working with dialogue groups, engaging farmers in data interpretation and passing the responsibility over elements of the research process to farmers, proved to be the most effective in strengthening farmers' involvement. The use of a simulation game to test innovations also showed promising results and should be explored further. The attitude of researchers proved to be an important factor in achieving a high level of farmers' engagement in the project. Copyright © 2020 John Wiley & Sons, Ltd.
Effect of Fertigation Frequency and Duration on Yield and Water Productivity of Wheat: Field and Modelling Study Using the Saltmed Model
Authors: Abdelraouf R.E. , Ragab R.
Published: February 2018

This study investigated the impact of fertigation frequency and fertigation time on wheat production. The field experiment included nine treatments over two seasons, 2014/2015 and 2015/2016. The same amount of water and nitrogen fertilizer was given for all treatments, either over 1 day, divided over 2 days or over 3 days. Three fertigation times (FT, period of injecting fertilizers in irrigation water) as a fraction of the irrigation period were also applied. In FT strategies, nitrogen is given either during the same period of the irrigation from the start to the end, at the last three‐quarters of the irrigation period or at the second half of the irrigation period, IT [FT = IT, FT = 0.75IT and FT = 0.5IT]. The observed and simulated nitrogen uptake and grain nitrogen content showed an increasing trend when fertigation frequencies increased and fertigation time decreased.The field and modelling results indicated that increasing fertigation frequencies and decreasing fertigation time have benefits particularly for sandy soils, including higher yields and less pollution. In conclusion, the use of the fertigation frequency of 3 days and fertilizer injection in the second half of the irrigation period is a good fertigation strategy for sandy soils. Copyright © 2018 John Wiley & Sons, Ltd.
Vibrio cholerae cytolysin: Multiple facets of the membrane interaction mechanism of a β‐barrel pore‐forming toxin
Authors: Kathuria Reema , Chattopadhyay Kausik
Published: February 2018

Vibrio cholerae cytolysin (VCC) is a membrane‐damaging protein toxin with potent cytolytic/cytotoxic activity against wide range of eukaryotic cells. VCC is a β‐barrel pore‐forming toxin (β‐PFT), and it inflicts damage to the target cell membranes by forming transmembrane heptameric β‐barrel pores. To exert pore‐forming activity, VCC must bind to the cell membranes in an efficient manner. Efficient interaction with the cell membranes is an essential pre‐requisite to trigger subsequent structural/conformational and organizational changes in the toxin molecules leading toward formation of the transmembrane oligomeric β‐barrel pores. Based on the large numbers of studies investigating the mode of action of VCC, it is now evident that VCC is capable of using multiple distinct mechanisms to recognize and bind to the membrane components and cell surface molecules. In this review article, we present an overview of our current understanding regarding the membrane interaction mechanisms of VCC, and their functional implications for the pore‐forming activity of the toxin. © 2018 IUBMB Life, 70(4):260–266, 2018
Controlling Cryptosporidium oocysts Using Conventional Treatment
Authors: Dugan Nicholas R. , Fox Kim R. , Owens James H. , Miltner Richard J.
Published: February 2018

Fourteen pilot‐scale tests were performed to assess the ability of conventional treatment to control Cryptosporidium oocysts and three surrogates: turbidity, total particle count, and aerobic endospores. Cryptosporidium oocysts were fed into the raw water at a target concentration of 106/L for 30–71 h in each test. The effects of coagulant type, coagulant dose, raw water quality, filter loading rates, and filter media were evaluated. Under optimal coagulation conditions, conventional treatment achieved more than 4‐log total Cryptosporidium removal, and surrogate log removals were conservative (low with respect to Cryptosporidium).
Calcium–Nom Loading onto Gac
Authors: Frederick Holly T. , Cannon Fred S.
Published: February 2018

This research evaluated how to minimize calcium (Ca) loading onto granular activated carbon (GAC) by adjusting pH and/or adding coagulants. Batch tests used raw water samples from New Castle, Pa. Total organic carbon (TOC) ranged from 4.0 to 5.3 mg/L. Variations in Ca loading reflected variability in natural organic matter composition between samples. For most samples, 5 mg/L of iron coagulant (as Fe) diminished Ca loading by 200–600 mg Ca/kg GAC—an 18–75% drop. In batch tests at constant pH with no coagulant and variable GAC doses, Ca loading increased linearly with TOC loading indicating that Ca and TOC adsorbed into GAC together. The ratio of Ca to TOC loaded onto GAC decreased with decreasing pH or increasing Fe. This showed that H+ or Fe(III) could displace the Ca that loaded with TOC and that utilities could diminish Ca loading by slightly depressing pH and/or by using moderate coagulant dosages.
Using Economic Loss Functions to Value urban water scarcity in California
Authors: Jenkins Marion W. , Lund Jay R. , Howitt Richard E.
Published: February 2018

Drought and dwindling supplies coupled with a growing population are severely straining California's water resources, and traditional water supply planning and analysis are proving inadequate to help the state prepare for future needs. To help ascertain the value of urban water use in California, one alternative has been the development of economic loss functions, which represent a flexible yet rigorous method to replace yield, shortage, and requirements‐based approaches to assessing water supply performance for planning studies, regulatory impact assessments, and other evaluations. The approach in this article applied residential water demand elasticities for residential willingness‐to‐pay for water, used an industry study for industrial willingness‐to‐pay for water, and assumed fixed commercial sector water use for 2020 population levels. On the basis of economic loss functions described in this article, urban water scarcity in California in 2020 would cost end users an estimated average of $1.6 billion per year, given current operations, allocations, and infrastructure.
Prioritizing watershed pathogen research
Authors: Ferguson Christobel , Altavilla Nanda , Ashbolt Nicholas J. , Deere Daniel A.
Published: February 2018

Water treatment professionals are generally aware of the issues regarding the fate and transport of pathogens within watersheds. However, not all water treatment professionals are in a scientific field nor do they all have the same level of knowledge of the range of international projects being conducted to address this issue. To counter a current lack of quantitative data on the biophysical and chemical parameters that drive pathogen survival and transport in watersheds, the authors created a conceptual model of a watershed that water suppliers can use as a starting point to create their own pathogen risk assessment and to prioritize their research to target identified knowledge gaps. These findings make it possible to identify the next steps for research and focus on the chemical, physical, and biological processes that underpin pathogen transport and attenuation while avoiding duplicative research efforts.
GAC pore structure in Cincinnati during full‐scale treatment/reactivation
Authors: Moore Brian C. , Cannon Fred S. , Metz Deborah H. , Demarco Jack
Published: February 2018

Granular activated carbon (GAC) was evaluated during full‐scale treatment operation at the Richard Miller Water Treatment Plant, Cincinnati, Ohio. Starting with virgin GAC, GAC was monitored through six treatment cycles and subsequent onsite thermal reactivation. Pore structure was monitored at the beginning and end of each cycle. Influent and effluent total organic carbon was measured during each cycle. During the first cycle, adsorption caused a large decrease only in micropore volume. With each subsequent cycle, the pore size that exhibited a decreasing volume shifted into larger pores. By the fourth cycle, net pore volume losses occurred in all pore sizes, with the most extensive losses in 100–300 Å pores. Yet, all GACs were similarly effective during treatment. After each cycle, reactivation seemed to influence pores of progressively larger widths. The virgin GAC was highly microporous, whereas after six reactivation cycles, the GAC was very mesoporous.
Sources of error in network modeling: a question of perspective
Authors: Filion Yves R. , Karney Bryan W.
Published: February 2018

This article explores and provides an overview of several important issues of uncertainty and error that arise in modeling water distribution systems. Initial emphasis is given to the ability and role of both the Hazen‐Williams and Darcy‐Weisbach friction models to describe hydraulic losses in a pipeline. Notwithstanding the suitability of these friction models, there exists a multitude of other uncertainties that can affect the accuracy of a hydraulic solution. A source of error often ignored during extended period simulation arises through the reservoir routing scheme used at storage elements. Other uncertainties stem from the way demands are represented (in both space and time), how the behavior of various hydraulic devices (such as valves and pumps) is emulated in simulation programs, and how the system's behavior is assumed to evolve in time. Persistent problems are also associated with aggregating demands, calibrating and skeletonizing systems, and gathering reliable field data. The problems associated with reservoir routing and system calibration are elucidated through more detailed numerical examples.
Utility‐based Analytical Methods to Ensure Public Water Supply Security
Authors: States Stanley , Scheuring Michele , Kuchta John , Newberry Jessica , Casson Leonard
Published: February 2018

Since the events of Sept. 11, 2001, the world has become a different place. More attention than ever is being paid to the nation's vulnerabilities, and this has prompted officials at all levels to examine the tools available for ensuring the security of public utilities. The recent emphasis on making sure that public water supplies are safe has created the need for continuous monitoring systems and analytical techniques that can be used at the utility level to test for a variety of toxic materials in a short amount of time. States and colleagues provide a survey of continuous monitoring and analytical methods currently available to utilities for security purposes. This survey grew out of an investigation the Pittsburgh (Pa.) Water & Sewer Authority (PWSA) and the University of Pittsburgh School of Engineering conducted in order to identify feasible analytical responses to security concerns. This investigation included a literature search; discussions with personnel from various water utilities, water industry organizations, and regulatory agencies; and evaluation of several commercially available monitoring and analytical systems. The article also takes a look at the analytical measures PWSA uses to screen for possible contamination in response to threats or suspected tampering with its water system as well as during times of heightened security. Although these methods are limited and their results should be interpreted with caution, there are some techniques, such as acute toxicity testing, that can be useful.
Using Treatment Residuals TO REDUCE PHOSPHORUS in agricultural runoff
Authors: Dayton Elizabeth A. , Basta Nicholas T. , Jakober Christopher A. , Hattey Jeffory A.
Published: February 2018

Drinking water treatment residuals can be beneficially used to reduce phosphorus (P) in runoff water from manured agricultural land. The objective of this study was to determine treatment residual components responsible for P sorption and reduction of P in runoff water. Using 21 aluminum‐ (Al‐) based treatment residuals from Oklahoma utilities, chemical components related to P sorption (amorphous Al [Alox, 1.33–48.7 g/kg], iron [Fe] [Feox, 0.23–7.44 g/kg] oxides), clay (0–100%), and water‐soluble calcium (0.05–0.74 g/kg) were measured. Linearized Langmuir P sorption maxima (Pmax) ranged from 0.30 to 5.14 g/kg, and nonlinear Freundlich P distribution coefficient (KP) ranged from 17.5 to 1,085 L/kg. Addition of water treatment residuals (50 Mg/ha) to box plots treated with poultry litter (16.7 Mg/ha) reduced runoff P by from 14.0 to 84.9%. Reductions in runoff P were strongly correlated (p < 0.05) with Pmax and Alox. Performance of treatment residuals as a P sorbent to reduce runoff P from manured land can be estimated from their Pmax or Alox content.
Use of Ozonation and FBT to control THM precursors
Authors: Yavich Alex A. , Masten Susan J.
Published: February 2018

This study evaluated ozonation in combination with biological fluidized‐bed treatment (FBT) for control of trihalomethane (THM) precursors in drinking water. THM precursors were represented by several surrogate parameters, including total organic carbon, ultraviolet absorbance measured at 254 nm, humic substances, and THM formation potential. The study was conducted using a continuously operated ozonation–FBT system. No pretreatment was provided. In addition, biofiltration and bench‐scale ozonation systems were used to compare the biodegradation efficiency of FBT with that of biofiltration and to investigate the effect of ozonation on biodegradation efficiency. The study showed that the combined ozonation–FBT process was effective in removing THM precursors and reducing turbidity in drinking water. Preliminary cost estimates indicate that the ozonation–FBT process may be a viable alternative to conventional coagulation processes that require additional steps, such as ozonation and biological activated carbon filtration for the control of disinfection by‐products in drinking water.
Metaphosphate reversion in Laboratory and Pipe‐Rig Experiments
Authors: Holm Thomas R. , Edwards Marc
Published: February 2018

Reversion of sodium metaphosphate was studied in two types of experiments. The “beaker” experiments used stoppered glass containers, pH‐buffered solutions, variable calcium (Ca) concentrations, and either 2 or 4 mg/L total phosphorus. The rate of orthophosphate [(PO4)–3] production increased as the Ca concentration increased. There was <10% reversion after 24 days for systems with no Ca, and >70% reversion for systems with 120 mg/L Ca. (PO4)–3 production was first‐order with respect to total polyphosphate. The rate constants were an approximately linear function of the logarithm of the Ca concentration. The “pipe‐rig” experiments used sections of copper and lead pipe that had been exposed to modified Boulder, Colo., tap water. Metaphosphate reversion was much more rapid in the pipe‐rig experiments than in the beaker experiments, and the rate of reversion increased substantially as the pipes aged over a period of years.
Effect of Ca on As release from Ferric and ALUM Residuals
Authors: Parks Jeffrey L. , Novak John , Macphee Michael , Itle Cortney , Edwards Marc
Published: February 2018

Dewatering of residuals containing arsenic (As) has attracted little research but will become increasingly important as As is removed from water by sorption to ferric or aluminum hydroxides. Lime conditioning proves to be an effective method for immobilizing As even at high pH. In contrast, increasing pH with addition of caustic soda or soda ash leaches As from residuals. Soluble calcium appears to neutralize the negative surface charge on the hydroxide solids to enhance As sorption. In many cases, As‐containing residuals are stored in lagoons for months or even years. Although many parameters contribute to soluble As mobilization, the presence of calcium appears to assist in keeping As immobilized.
Approaching DBP toxicity as a mixtures problem
Authors: Teuschler Linda K. , Simmons Jane Ellen
Published: February 2018

Positive epidemiologic and toxicologic studies underline the need for assessment of human health risks from ubiquitous exposures to mixtures of disinfection by‐products (DBPs). Typical human exposures to DBPs are at extremely low levels; thus, health risk is likely to be attributable to multiple, rather than single, DBP exposures. This article suggests three approaches to evaluating health risks from DBP mixtures: (1) toxicologic studies of simple defined mixtures, (2) toxicologic studies using reproducible disinfection scenario samples, and (3) toxicologic or epidemiologic studies conducted directly on drinking water samples. The authors believe all three approaches are valid and can provide data applicable to DBP risk assessment. They also postulate that single‐chemical toxicologic studies are, by themselves, insufficient to fully characterize DBP health risks. A concentrated effort by a multidisciplinary team of researchers is necessary to generate appropriate DBP mixtures health data.