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1.
Phytopathology ; 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38015417

ABSTRACT

Identifying the precise pathogens responsible for specific plant diseases is imperative for implementing targeted and efficient interventions and mitigating their spread. Dieback and shoot blight significantly diminish the lifespan and productivity of blueberries, yet the causative agents remain largely unidentified. To determine the identity and prevalence of the causal agents of branch dieback and shoot blight, we conducted multi-year and multi-site sampling of diseased highbush blueberries (Vaccinium corymbosum cv. Duke) in Serbia. Sixty-nine monosporic isolates were collected and characterized based on morphological, physiological features and multi-locus phylogenetic analysis of internal transcribed spacer (ITS), ß-tubulin (TUB2) and translation elongation factor 1-alpha (TEF1) sequence data. Five species were identified as causal agents: Diaporthe eres (36 isolates), D. foeniculina (3 isolates), Neopestalotiopsis vaccinii (9 isolates), N. rosae (6 isolates) and Neofusicoccum parvum (15 isolates). The results of the pathogenicity tests performed with the 23 representative isolates confirmed the role of these species as primary pathogens in causing dieback and shoot blight of blueberry, with N. parvum being the most aggressive and D. eres the least. Our study underscores the diversity of genera and species of ascomycetes capable of causing blueberry dieback and shoot blight. Furthermore, our findings indicate that the agents responsible for the disease in Serbia differ from those identified in other regions worldwide.

3.
Environ Sci Technol ; 57(13): 5190-5202, 2023 04 04.
Article in English | MEDLINE | ID: mdl-36966415

ABSTRACT

Emerging lead halide perovskite (LHP) photovoltaics are undergoing intense research and development due to their outstanding efficiency and potential for low manufacturing costs that render them competitive with existing photovoltaic (PV) technologies. While today's efforts are focused on stability and scalability of LHPs, the toxicity of lead (Pb) remains a major challenge to their large-scale commercialization. Here, we present a screening-level, EPA-compliant model of fate and transport of Pb leachate in groundwater, soil, and air, following hypothetical catastrophic breakage of LHP PV modules in conceptual utility-scale sites. We estimated exposure point concentrations of Pb in each medium and found that most of the Pb is sequestered in soil. Exposure point concentrations of Pb from the perovskite film fell well below EPA maximum permissible limits in groundwater and air even upon catastrophic release from PV modules at large scales. Background Pb levels in soil can influence soil regulatory compliance, but the highest observed concentrations of perovskite-derived Pb would not exceed EPA limits under our assumptions. Nonetheless, regulatory limits are not definitive thresholds of safety, and the potential for increased bioavailability of perovskite-derived Pb may warrant additional toxicity assessment to further characterize public health risks.


Subject(s)
Calcium Compounds , Lead , Biological Availability , Soil
4.
Am J Obstet Gynecol ; 227(6): 805-811, 2022 12.
Article in English | MEDLINE | ID: mdl-35934117

ABSTRACT

Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration-approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.


Subject(s)
Biosimilar Pharmaceuticals , COVID-19 , Pregnancy , Female , Adult , United States , Humans , United States Food and Drug Administration , Morals
5.
Eur J Pediatr ; 181(3): 1143-1149, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34757451

ABSTRACT

To determine the perception of children with inflammatory bowel disease (IBD) regarding monitoring tests, we first compared the reported discomfort and patient perspective during gastro-intestinal (GI)-endoscopy, magnetic resonance entrography (MRE), and ultrasound (US) and, in a second comparison, patient preference on non-invasive tests (venipuncture, sampling stool and US). A cross-sectional study in children 8-18 years undergoing an US, MRE, and GI-endoscopy for diagnosis or follow-up of IBD. After each procedure, the children filled out the Discomfort during research procedures questionnaire (DISCO-RC). Items of the DISCO-RC are as follows: nervousness, annoyance, pain, fright, boredom, and tiredness. Answers range from "not" (= 0 points) to "extremely" (= 4 points) (range total score: 0-24). Differences between the procedures were assessed with Friedman test, with subsequent Wilcoxon signed-rank test. The children were also asked which non-invasive test they preferred not to undergo regularly (venipuncture, stool-sampling, or US). Answers were analyzed with χ2-test. Forty-nine patients (27 (55%) female, median age 15 (range 9-17)) were included. The children reported to be most nervous, frightened, and tired after GI-endoscopy (median: 1, 1, 2 points, respectively), equally annoyed by MRE and GI-endoscopy (median 1 point), and equally bored by MRE and US. GI-endoscopy was ranked as most discomfortable, followed by MRE and US (total DISCO-RC scores: 7 vs. 5 vs. 2, p < 0.001). Most of the children preferred not to sample stool or perform venipuncture regularly (n = 20 (41%, both) (p < 0.001)).Conclusion: Our results suggest that the children with IBD report low discomfort after US, MRE, and GI-endoscopy. US is preferred as a monitoring tool, also among non-invasive monitoring tests. GI-endoscopy was most discomfortable. What is Known: • Children with inflammatory bowel disease need to be monitored frequently for disease activity. • Adult studies - including a systematic review - on acceptability of monitoring tools among IBD patients showed mixed results. What is New: • Children in our study ranked gastro-intestinal endoscopy as most discomfortable, followed by MRE and US. • With regard to non-invasive monitoring, most children preferred not to sample stool or perform venipuncture regularly, and preferred US.


Subject(s)
Inflammatory Bowel Diseases , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Inflammatory Bowel Diseases/diagnosis , Magnetic Resonance Imaging/methods , Perception , Ultrasonography/methods
6.
Nat Commun ; 12(1): 3196, 2021 05 27.
Article in English | MEDLINE | ID: mdl-34045457

ABSTRACT

Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria - Plasmodium falciparum. We reveal developmental trajectories associated with the colonization of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and non-conserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, provide a fine-grained atlas that enables intensive investigation of the P. falciparum transcriptional journey. As well as providing insights into gene function across the transmission cycle, the atlas opens the door for identification of drug and vaccine targets to stop malaria transmission and thereby prevent disease.


Subject(s)
Anopheles/parasitology , Life Cycle Stages/genetics , Malaria, Falciparum/transmission , Mosquito Vectors/parasitology , Plasmodium falciparum/genetics , Animals , Antimalarials/pharmacology , Antimalarials/therapeutic use , Female , Host-Parasite Interactions/genetics , Humans , Life Cycle Stages/drug effects , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Male , Plasmodium falciparum/drug effects , Plasmodium falciparum/pathogenicity , RNA-Seq , Single-Cell Analysis , Species Specificity , Transcriptome/drug effects
7.
Biol Imaging ; 1: e2, 2021.
Article in English | MEDLINE | ID: mdl-35036920

ABSTRACT

Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.

8.
Med Chem ; 17(5): 442-452, 2021.
Article in English | MEDLINE | ID: mdl-31808389

ABSTRACT

BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase). OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method. RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 µM and 68.7 µM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288. CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.


Subject(s)
Chalcones/chemistry , Cholinesterase Inhibitors/chemistry , Acetylcholinesterase/metabolism , Animals , Butyrylcholinesterase/metabolism , Chalcones/chemical synthesis , Chalcones/metabolism , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/metabolism , Enzyme Assays , Humans , Molecular Docking Simulation , Molecular Structure , Protein Binding , Structure-Activity Relationship , Torpedo
9.
Contraception ; 102(5): 308-313, 2020 11.
Article in English | MEDLINE | ID: mdl-32534968

ABSTRACT

OBJECTIVES: Although a body of research has focused on violence, disruption, and harassment targeting abortion clinics and clinic staff, little research has explored Canadian abortion patients' experiences with protesters. Through this national qualitative study we aimed to address this gap. METHODS: Between 2012 and 2016, we conducted in-depth interviews with 305 Canadian women who had an abortion in the previous five years. Thirty participants reported encountering protesters when seeking abortion care. We focused on this sub-set of interviews and analyzed these data for content and themes using inductive and deductive techniques. RESULTS: Across the country, participants reported encountering protesters holding signs, chanting slogans, and shouting insults. These interactions were concentrated at clinics in New Brunswick, Newfoundland and Labrador, and Ontario. Although no participants reported that these encounters made them reconsider their decision, they did report that seeing and interacting with protesters was at times unsettling, stigmatizing, and frustrating. Participants who struggled with the decision to have an abortion and those who made the decision in the context of health issues or violence found these encounters especially upsetting. Participants discussed how their interactions with protesters and the additional security measures put in place by clinics contrasted with their experiences accessing other kinds of health care and they wished that the protesters had not been there. CONCLUSIONS: For some Canadian abortion patients, encountering protesters is upsetting and stigmatizing. Exploring ways to minimize interactions between protesters and those seeking abortion care, such as enacting and enforcing safe access zone legislation, appears warranted. IMPLICATIONS: Although several Canadian provinces have enacted safe access zone laws, these do not currently exist across all jurisdictions. In addition to protecting clinics and clinic staff, implementation of these buffer zones have the potential to improve some patients' experiences obtaining a medically necessary and essential service.


Subject(s)
Abortion, Induced , Health Services Accessibility , Ambulatory Care Facilities , Emotions , Female , Humans , Ontario , Pregnancy , Qualitative Research
10.
Int J Biol Macromol ; 165(Pt B): 2541-2549, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33736274

ABSTRACT

Objects of the present study are improved fullerene C60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C60 and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C60. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C60-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C60 potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.


Subject(s)
Cell Culture Techniques/methods , Fructans/chemistry , Glucans/chemistry , Hyaluronic Acid/chemistry , Maleates/chemistry , Adsorption , Cell Adhesion , Cell Proliferation , Diphenhydramine/chemistry , Hep G2 Cells , Humans , Hydrogels , Lidocaine/chemistry , Propranolol/chemistry , Spectroscopy, Fourier Transform Infrared , Synchrotrons
11.
J Pediatr Urol ; 15(5): 531-545, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31542362

ABSTRACT

INTRODUCTION: Some patients with diseases that involve increased bladder pressure or low-capacity bladders may need bladder enlargement surgery. In current techniques for bladder enlargement, autologous tissue such as small intestine or colon tissue is used to perform cystoplasties, which is far from ideal for these patients. In search of biomaterials with appropriate regeneration and safety profiles, tissue engineering has resulted in preclinical studies with acellular matrices in animal models that have yielded positive preliminary results with respect to the urothelial cell and smooth muscle repopulation; these studies have primarily been performed with matrices originating from the bladder or intestinal submucosa. OBJECTIVE: The aim of the study was to assess an extracellular matrix device derived from the porcine esophagus for augmentation cystoplasty in an animal model. STUDY DESIGN: Seven male Wistar rats weighing 357-390 g were subjected to augmentation cystoplasty with a circular segment of the acellular matrix from the porcine esophagus. Daily postoperative follow-up was performed with evaluation of changes in body weight, behavior, and wound status. RESULTS: During follow-up, there were no complications associated with the process. Three specimens were sacrificed at day 30, and three, at day 60. Necropsy was performed, with a description of the macroscopic findings and a morphological study. Epithelialization was observed, with different stages of mucosal development in all specimens analyzed. Repopulation of smooth muscle cells, mixed inflammatory infiltrate, and vascular neoformation were identified in the matrices. DISCUSSION: The urothelium and fibers of the smooth muscle were observed inside the implanted matrix. Additional investigations in larger animal models that allow urodynamic evaluation of the bladder with the matrix implanted are needed. However, to compare the results of this study model with those reported in the literature, a matrix derived from an organ different from the bladder was used because it could prevent the use of an intestinal segment in augmentation cystoplasty. CONCLUSION: The acellular porcine esophagus matrix offers positive results regarding the repopulation of the urothelium and smooth muscle when used in augmentation cystoplasty in a murine model.


Subject(s)
Extracellular Matrix/transplantation , Urinary Bladder/surgery , Animals , Esophagus/cytology , Male , Models, Animal , Rats, Wistar , Swine , Urologic Surgical Procedures/methods
12.
Science ; 364(6437): 283-285, 2019 Apr 19.
Article in English | MEDLINE | ID: mdl-31000662

ABSTRACT

Malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. For example, BAP1 encodes a widely expressed deubiquitinase for histone H2A, but germline mutations are predominantly associated with uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. In contrast, BAP1 loss in melanocytes had little impact on expression of prosurvival genes, instead inducing Mitf Thus, BAP1 appears to modulate gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program.


Subject(s)
Apoptosis/genetics , Carcinogenesis/genetics , Gene Expression Regulation, Neoplastic , Melanoma/genetics , Polycomb Repressive Complex 1/metabolism , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Ubiquitin-Protein Ligases/metabolism , Uveal Neoplasms/genetics , Animals , Gene Knock-In Techniques , Germ-Line Mutation , Histones , Humans , Melanocytes/metabolism , Melanocytes/pathology , Melanoma/pathology , Mesothelioma/genetics , Mesothelioma/pathology , Mice , Mice, Mutant Strains , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Ubiquitination , Uveal Neoplasms/pathology
13.
Pigment Cell Melanoma Res ; 32(2): 269-279, 2019 03.
Article in English | MEDLINE | ID: mdl-30156010

ABSTRACT

The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low frequency. In addition, Bap1-null melanoma cells derived from mouse tumors are more aggressive and colonize and grow at distant sites more than their wild-type counterparts. Molecularly, Bap1-null melanoma cell lines have increased DNA damage measured by γH2aX and hyperubiquitination of histone H2a. Therapeutically, these Bap1-null tumors are completely responsive to BRAF- and MEK-targeted therapies. Therefore, BAP1 functions as a tumor suppressor and limits tumor progression in melanoma.


Subject(s)
Carcinogenesis/genetics , Carcinogenesis/pathology , Melanoma/genetics , Melanoma/pathology , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Tumor Suppressor Proteins/metabolism , Ubiquitin Thiolesterase/metabolism , Animals , Cell Line, Tumor , Cell Proliferation , DNA Damage , Epithelial-Mesenchymal Transition/genetics , Gene Deletion , Gene Expression Regulation, Neoplastic , Histones/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Melanocytes/metabolism , Melanocytes/pathology , Mice, Inbred C57BL , Mice, Knockout , Transcription, Genetic , Ubiquitination , Melanoma, Cutaneous Malignant
14.
Endocr Pract ; 25(1): 51-54, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30383491

ABSTRACT

OBJECTIVE: To analyze the frequency and nature of after-hours calls to endocrinology fellows and employ interventions to direct appropriate care to primary endocrinologists. METHODS: The on-call fellows logged calls that came to them during the after-hours and marked them as urgent or nonurgent. We analyzed these calls and then implemented interventions to educate patients on calls that can wait until the next business day. We also trained providers to provide script refills during clinic visits and educated fellows on how to best manage and document these after-hours calls. RESULTS: From July to August 2017, 100 calls were logged. The average number of calls per 24 hours was 1.61, and 47% were marked nonurgent. From January to March 2018, the fellows logged 0.64 calls per 24 hours, and 51% were logged as nonurgent. Most of these calls were for insulin and testing supply refills. CONCLUSION: Many after-hours calls to the fellows were nonurgent and could have waited until the next business day. Our continuing interventions aim at improving both physician and patient satisfaction, as well as patient care.


Subject(s)
Endocrinology , Physicians , Ambulatory Care , Humans , Telephone
15.
Eur J Pediatr ; 178(2): 207-211, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30392051

ABSTRACT

Research in children should strike the right balance between protecting underage study subjects and advancing the medical field. This study gives insight into the emotional burden that common invasive research procedures in asthma research have on young children, both from the child and parent perspective. Puppetry was used to stimulate children (age 5-6 years) to explain their emotional burden prior to and after the research procedures. We operationalised emotional burden as willingness to participate in future research and reluctance towards participation. Parents filled out a questionnaire on this topic. Symptomatic patients as well as healthy controls were analysed. Forty-one children were included. Children's anticipatory fear for future research showed a clear decrease of 0.7 ± 1.6 on a 5-point Likert scale as a consequence of participation (p = 0.02). Sixty percent of all participating children explicitly indicated willingness to undergo identical research procedures again. Children uninformed by their parents about the venipuncture were significantly more reluctant to the venipuncture after the procedure (p < 0.01), compared to children who had been informed (4.0 ± 0.9 resp. 2.8 ± 1.2).Conclusion: This study suggests that the emotional burden of participation in asthma research for underage children can be prevented when they are properly informed and decreases as a consequence of participations. We believe increased emphasis should be placed on informing children and evaluating the emotional impact of research to help caretakers and research ethics committees make informed decisions about participation of children in medical research. What is Known: • Medical professionals and parents are likely to overestimate children's discomfort undergoing (invasive) research procedures. • Two thirds of children (age 6-18 years) participating in medical research indicated that they would participate in the same research study again. What is New: • Pre-school children experience little emotional burden during invasive procedures in asthma research. • Proper communication about (invasive) research procedures in pre-school children helps to reduce the anticipatory fear of these procedures in the future.


Subject(s)
Asthma/psychology , Emotions , Patient Participation/psychology , Phlebotomy/psychology , Research Subjects/psychology , Biomedical Research/statistics & numerical data , Child , Child, Preschool , Ethics, Research , Female , Humans , Male , Parents , Play and Playthings , Surveys and Questionnaires , Visual Analog Scale
16.
Article in English | MEDLINE | ID: mdl-29710821

ABSTRACT

This study identified and prioritized potential failure scenarios for natural gas drilling operations through an elicitation of people who work in the industry. A list of twelve failure scenarios of concern was developed focusing on specific events that may occur during the shale gas extraction process involving an operational failure or a violation of regulations. Participants prioritized the twelve scenarios based on their potential impact on the health and welfare of the general public, potential impact on worker safety, how well safety guidelines protect against their occurrence, and how frequently they occur. Illegal dumping of flowback water, while rated as the least frequently occurring scenario, was considered the scenario least protected by safety controls and the one of most concern to the general public. In terms of worker safety, the highest concern came from improper or inadequate use of personal protective equipment (PPE). While safety guidelines appear to be highly protective regarding PPE usage, inadequate PPE is the most directly witnessed failure scenario. Spills of flowback water due to equipment failure are of concern both with regards to the welfare of the general public and worker safety as they occur more frequently than any other scenario examined in this study.


Subject(s)
Natural Gas , Oil and Gas Industry/organization & administration , Humans , Oil and Gas Industry/standards , Wastewater/analysis , Water Pollutants, Chemical/analysis
17.
Article in English | MEDLINE | ID: mdl-29641504

ABSTRACT

Identifying sources of concern and risk from shale gas development, particularly from the hydraulic fracturing process, is an important step in better understanding sources of uncertainty within the industry. In this study, a risk assessment of residential exposure pathways to contaminated drinking water is carried out. In this model, it is assumed that a drinking water source is contaminated by a spill of flowback water; probability distributions of spill size and constituent concentrations are fit to historical datasets and Monte Carlo simulation was used to calculate a distribution of risk values for two scenarios: (1) use of a contaminated reservoir for residential drinking water supply and (2) swimming in a contaminated pond. The swimming scenario did not produce risks of concern from a single exposure of 1 h duration, but 11 such 1-h exposures did produce risks of 10-6 due to radionuclide exposure. The drinking water scenario over a 30-year exposure duration produced cancer risk values exceeding 10-6 for arsenic, benzene, benzo(a)pyrene, heptachlor, heptachlor epoxide, pentachlorophenol, and vinyl chloride. However, this extended exposure duration is probably not realistic for exposure by a spill event. Radionuclides produced risks in the residential drinking water scenario of 10-6 in just 8 h, a much more realistic timeline for continual exposure due to a spill event. In general, for contaminants for which inhalation exposure was applicable, this pathway produced the highest risks with exposure from ingestion posing the next greatest risk to human health followed by dermal absorption (or body emersion for radionuclides). Considering non-carcinogenic effects, only barium and thallium exceed target limits, where the ingestion pathway seems to be of greater concern than dermal exposure. Exposure to radionuclides in flowback water, particularly through the inhalation route, poses a greater threat to human health than other contaminants examined in this assessment and should be the focus of risk assessment and risk mitigation efforts.


Subject(s)
Carcinogens , Environmental Exposure , Hydraulic Fracking , Neoplasms/chemically induced , Water Pollution , Benzene , Drinking Water , Humans , Inhalation Exposure , Monte Carlo Method , Natural Gas , Risk Assessment , Swimming Pools , Wastewater , Water , Water Pollutants, Chemical , Water Supply
18.
J Org Chem ; 83(4): 2166-2172, 2018 02 16.
Article in English | MEDLINE | ID: mdl-29359560

ABSTRACT

The reactivity of the C2v-symmetric pentakisadduct of C60 with azomethine ylides and conjugated dienes was studied experimentally and computationally. This derivative possesses four [6,6] double bonds, each with unique electrophilicity. The Diels-Alder reaction studied is a regiospecific, kinetically and thermodynamically guided [4 + 2] process producing [5:1]-hexaadducts with an octahedral addition pattern. The kinetically controlled Prato reaction gives a mixture of regioisomeric [5:1]-hexaadducts. The synthesis of geometrically well-defined supramolecular architectures may benefit from these new types of highly functionalized [5:1]-hexaadducts.

19.
BMC Pediatr ; 17(1): 199, 2017 Nov 29.
Article in English | MEDLINE | ID: mdl-29187148

ABSTRACT

BACKGROUND: There is a need for data on children's self-reported discomfort in clinical research, helping ethics committees to make their evaluation of discomfort described in study protocols evidence-based. Since there is no appropriate instrument to measure children's discomfort during medical research procedures, we aimed to develop a generic, short and child-friendly instrument: the DISCO-RC questionnaire (DISCOmfort in Research with Children). METHODS: This article describes the six steps of the development of the DISCO-RC. First, we updated a literature search on children's self-reported discomfort in clinical research to get insight in what words are used to measure discomfort (step 1). Subsequently, we interviewed 46 children (6-18 years) participating in research to get insight into important forms of discomfort for children (step 2), and asked them about their preferred response option for measuring discomfort (step 3). Next, we consulted nine paediatric research professionals from various backgrounds for input on the content and feasibility of the DISCO-RC (step 4). Based on the previous steps, we developed a draft version of the DISCO-RC, which we discussed with the professionals. The DISCO-RC was then pretested in 25 children to ensure face-validity from the child's perspective and feasibility (step 5). Finally, validity, reliability and internal consistency were tested (step 6). RESULTS: The search-update revealed several words used for measuring discomfort in research (e.g. 'worries', 'unpleasantness'). The interviews gave insight into important forms of discomfort for children in research (e.g. 'pain', 'boredom'). Children preferred a 5-point Likert scale as response option for the DISCO-RC. The experts recommended a short, digital instrument involving different forms of discomfort, and measuring discomfort of individual research procedures. Pretesting of the DISCO-RC resulted in a few layout changes, and feedback from the children confirmed the feasibility of the DISCO-RC. Convergent validity and test-retest reliability were acceptable. Internal consistency based on item-rest correlations and Cronbach's alpha were low, as expected. CONCLUSIONS: The DISCO-RC is a generic, practical and psychometrically sound instrument for measuring children's discomfort during research procedures. It contributes to make the evaluation of discomfort in paediatric research evidence-based. Therefore, we recommend including the DISCO-RC as standard component of paediatric research studies.


Subject(s)
Anxiety/diagnosis , Boredom , Fatigue/diagnosis , Human Experimentation/ethics , Pain Measurement/methods , Research Subjects/psychology , Self Report , Adolescent , Anxiety/etiology , Child , Fatigue/etiology , Female , Humans , Interviews as Topic , Male , Pain Measurement/ethics , Psychometrics , Qualitative Research , Reproducibility of Results
20.
Environ Sci Technol ; 51(22): 13344-13352, 2017 Nov 21.
Article in English | MEDLINE | ID: mdl-29053261

ABSTRACT

Data collected from experiments conducted at a flask scale are regularly used as input data for life cycle assessments and techno-economic analyses for predicting the potential productivities of large-scale commercial facilities. This study measures and compares nitrogen removal and biomass growth rates in treatment systems that utilize an algae-bacteria consortium to remediate landfill leachate at three scales: small (0.25 L), medium (100 L), and large (1000 L). The medium- and large-scale vessels were run for 52 consecutive weeks as semibatch reactors under variable environmental conditions. The small-scale experiments were conducted in flasks as batch experiments under controlled environmental conditions. Kolomogov-Smirnov statistical tests, which compare the distributions of entire data sets, were used to determine if the ammonia removal, total nitrogen removal, and biomass growth rates at each scale were statistically different. Results from the Kolmogov-Smirnov comparison indicate that there is a significant difference between all rates determined in the large-scale vessels compared to those in the small-scale vessels. These results suggest that small-scale experiments may not be appropriate as input data in predictive analyses of full scale algal processes. The accumulation of nitrite and nitrate within the reactor, observed midway through the experimental process, is attributed to high relative abundances of ammonia- and nitrite-oxidizing bacteria, identified via metagenomic analysis.


Subject(s)
Bioreactors , Nitrogen , Water Pollutants, Chemical , Ammonia , Bacteria , Biomass
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