Evaluation of a Novel Approach for Reducing Emissions of Pharmaceuticals to the Environment

Increased interest over the levels of pharmaceuticals detected in the environment has led to the need for new approaches to manage their emissions. Inappropriate disposal of unused and waste medicines and release from manufacturing plants are believed to be important pathways for pharmaceuticals entering the environment. In situ treatment technologies, which can be used on-site in pharmacies, hospitals, clinics, and at manufacturing plants, might provide a solution. In this study we explored the use of Pyropure, a microscale combined pyrolysis and gasification in situ treatment system for destroying pharmaceutical wastes. This involved selecting 17 pharmaceuticals, including 14 of the most thermally stable compounds currently in use and three of high environmental concern to determine the technology’s success in waste destruction. Treatment simulation studies were done on three different waste types and liquid, solid, and gaseous emissions from the process were analyzed for parent pharmaceutical and known active transformation products. Gaseous emissions were also analyzed for NOx, particulates, dioxins, furans, and metals. Results suggest that Pyropure is an effective treatment process for pharmaceutical wastes: over 99 % of each study pharmaceutical was destroyed by the system without known active transformation products being formed during the treatment process. Emissions of the other gaseous air pollutants were within acceptable levels. Future uptake of the system, or similar in situ treatment approaches, by clinics, pharmacists, and manufacturers could help to reduce the levels of pharmaceuticals in the environment and reduce the economic and environmental costs of current waste management practices

Complementarity of Galactic radio and collider data in constraining WIMP dark matter models

In this work we confront dark matter models to constraints that may be derived from radio synchrotron radiation from the Galaxy, taking into account the astrophysical uncertainties and we compare these to bounds set by accelerator and complementary indirect dark matter searches. Specifically we apply our analysis to three popular particle physics models. First, a generic effective operator approach, in which case we set bounds on the corresponding mass scale, and then, two specific UV completions, the Z' and Higgs portals. We show that for many candidates, the radio synchrotron limits are competitive with the other searches, and could even give the strongest constraints (as of today) with some reasonable assumptions regarding the astrophysical uncertainties.Comment: 22 pages, 12 figure

Review: The Newsletter of the Literary Managers and Dramaturgs of the Americas, volume 14, issue 1

Contents include: Far From Inundated, A Word form the President, BHAGS Words of Welcome, Remarks from Conference Co-Chair Ed Sobel, Keynote Speech Given by Chuck Smith Introduced by Michele Volansky, The Telephone Monologues: Five Monologues Written for the 2003 LMDA Conference introduced by Janet Allard, Telephone, Billy, The Visitors, A Drag Queen, Choice, Don\u27t Know Much About Holly-turgy Outline, Reflections on Conference 2003, Elect Better Actors, Neo-Romantic Manifesto, Pullet Surprise-Call for Nominations, and Regional News-Know Your Regional Vice Presidents. Issue editors: D.J. Hopkins, Shelley Orr, Liz Engelman, Madeleine Oldham, Jacob Zimmerhttps://soundideas.pugetsound.edu/lmdareview/1028/thumbnail.jp

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas

<p>Abstract</p> <p>Background</p> <p>The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas.</p> <p>Methods</p> <p>The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry.</p> <p>Results</p> <p>Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 ± 0.74 (p < 0.01) and 6.25 ± 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 ± 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 ± 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 ± 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size.</p> <p>Conclusions</p> <p>We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression.</p

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Reality Monitoring and Metamemory in Adults with Autism Spectrum Conditions.

Studies of reality monitoring (RM) often implicate medial prefrontal cortex (mPFC) in distinguishing internal and external information, a region linked to autism-related deficits in social and self-referential information processing, executive function, and memory. This study used two RM conditions (self-other; perceived-imagined) to investigate RM and metamemory in adults with autism. The autism group showed a deficit in RM, which did not differ across source conditions, and both groups exhibited a self-encoding benefit on recognition and source memory. Metamemory for perceived-imagined information, but not for self-other information, was significantly lower in the autism group. Therefore, reality monitoring and metamemory, sensitive to mPFC function, appear impaired in autism, highlighting a difficulty in remembering and monitoring internal and external details of past events.This research was supported by a James S. McDonnell Scholar Award to J.S.S., and an Economic and Social Research Council Award to R.A.C