Applying a 4D multiscale in vivo tumor growth model to the exploration of radiotherapy scheduling: The effects of weekend treatment gaps and p53 gene status on the response of fast growing solid tumors

The present paper aims at demonstrating clinically oriented applications of the multiscale four dimensional in vivo tumor growth simulation model previously developed by our research group. To this end the effect of weekend radiotherapy treatment gaps and p53 gene status on two virtual glioblastoma tumors differing only in p53 gene status is investigated in silico. Tumor response predictions concerning two rather extreme dose fractionation schedules (daily dose of 4.5 Gy administered in 3 equal fractions) namely HART (Hyperfractionated Accelerated Radiotherapy weekend less) 54 Gy and CHART (Continuous HART) 54 Gy are presented and compared. The model predictions suggest that, for the same p53 status, HART 54 Gy and CHART 54 Gy have almost the same long term effects on locoregional tumor control. However, no data have been located in the literature concerning a comparison of HART and CHART radiotherapy schedules for glioblastoma. As non small cell lung carcinoma (NSCLC) may also be a fast growing and radiosensitive tumor, a comparison of the model predictions with the outcome of clinical studies concerning the response of NSCLC to HART 54 Gy and CHART 54 Gy is made. The model predictions are in accordance with corresponding clinical observations, thus strengthening the potential of the model

TiO2-carbon microspheres as photocatalysts for effective remediation of pharmaceuticals under simulated solar light

In this work, novel carbon microspheres supported TiO2 nanoparticles were prepared for the degradation of pharmaceuticals in water, selecting diclofenac, acetaminophen, and ibuprofen as target pollutants. Lignin, an important biomass byproduct from the paper industry and biorefineries, was transformed in carbon microspheres by a novel approach based on a Fe-activated hydrothermal carbonization followed by pyrolysis at 900 °C. These carbon microspheres were further covered with TiO2 by a solvothermal treatment. The effects of several parameters including hydrothermal carbonization time and mass ratio (TiO2:carbon) on the catalytic activity of TiO2-carbon microspheres were investigated. The results revealed that the combination of long carbonization time and high TiO2:carbon ratio achieved superior TiO2-carbon microspheres (Ti2-C20) catalytic performance. Ti2-C20 achieved complete degradation of ibuprofen (5 mg·L−1) and diclofenac (5 mg·L−1) within 3 h under solar light and mineralization percentages close to 50%. Moreover, the photocatalytic performance remained high after five reuse cycles and was barely affected by the presence of common inorganic ions in treated wastewater (such as Cl–, NO3– and HCO3–). The degradation pathway of diclofenac was proposed, involving C-N bond cleavage, and subsequent hydroxylation and cyclization reactions leading to the formation of aliphatic carboxylic acids. Overall, promising photocatalysts were obtained from a biomass byproduct for effective degradation of pharmaceuticals with the assistance of solar lightThis research was funded by the Spanish State Research Agency (PID2019-106186RB-I00/AEI/10.13039/501100011033). M. Peñas-Garzón is indebted to Spanish MECD for a FPU grant (FPU16/00576 grant) and to Spanish MICIU for funding the international stay (EST18/00048 grant) at the Department of Chemical and Environmental Engineering (ChEE), University of Cincinnati. Authors thank the Research Support Services of the University of Extremadura (SAIUEx) for its technical and scientific suppor

Introduction of Hypermatrix and Operator Notation into a Discrete Mathematics Simulation Model of Malignant Tumour Response to Therapeutic Schemes In Vivo. Some Operator Properties

The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators’ commutativity and outline the “summarize and jump” strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83–02, thus strengthening the reliability of the model developed

Degradation of contaminants of emerging concern by UV/H2O2 for water reuse: Kinetics, mechanisms, and cytotoxicity analysis.

Advanced oxidation using UV and hydrogen peroxide (UV/H2O2) has been widely applied to degrade contaminants of emerging concern (CECs) in wastewater for water reuse. This study investigated the degradation kinetics of mixed CECs by UV/H2O2 under variable H2O2 doses, including bisphenol A, estrone, diclofenac, ibuprofen, and triclosan. Reverse osmosis (RO) treated water samples from Orange County Water District's Groundwater Replenishment System (GWRS) potable reuse project were collected on different dates and utilized as reaction matrices with spiked additions of chemicals (CECs and H2O2) to assess the application of UV/H2O2. Possible degradation pathways of selected CECs were proposed based on high resolution mass spectrometry identification of transformation products (TPs). Toxicity assessments included cytotoxicity, aryl hydrocarbon receptor-binding activity, and estrogen receptor-binding activity, in order to evaluate potential environmental impacts resulting from CEC degradation by UV/H2O2. Cytotoxicity and estrogenic activity were significantly reduced during the degradation of mixed CECs in Milli-Q water by UV/H2O2 with high UV fluence (3200 mJ cm-2). However, in GWRS RO-treated water samples collected in April 2017, the cytotoxicity and estrogen activity of spiked CEC-mixture after UV/H2O2 treatment were not significantly eliminated; this might be due to the high concentration of target CEC and their TPs, which was possibly affected by the varied quality of the secondary treatment influent at this facility such as sewer-shed and wastewater discharges. This study aimed to provide insight on the impacts of post-UV/H2O2 CECs and TPs on human and ecological health at cellular level

Routine dynamics in virtual teams: the role of technological artifacts

Purpose In this paper, the authors extend their understanding of the internal dynamics of routines in contexts characterized by increased levels of virtuality. In particular, the authors focus on the role of routine artifacts in the internal dynamics of routines to answer the question: How does extensive reliance on information and communication technologies (ICTs) due to physical distance influence the internal dynamics of the new product development (NPD) routine (i.e. interactions between performative, ostensive and artifacts of routines) enacted by a virtual team? Design/methodology/approach This paper is based on an 18-month ethnographic study of the NPD routine performed by a virtual team. The authors relied predominantly on qualitative, ethnographic data collection and analysis methods, using semi-structured interviews, non-participant observation, and the collection of archival data and company documents (formal procedures, guidelines, application designs etc). Qualitative research offers a valuable means to investigate dynamic processes in organizations due to its sensitivity to the organizational context and potential to focus on activities as they unfold. Findings The findings highlight the central role of routine artifacts (ICTs) in the routine dynamics of the NPD routine performed by virtual team. In particular, the authors show that the use of the particular types of ICTs enabled team members to confidently and meaningfully relate to the overall routine activity and coordinate their actions in a context characterized by physical distance and extensive reliance on communication and collaboration technologies. Originality/value The paper sheds light into role of routine artifacts in the routine dynamics in a context characterized by a high degree of virtuality. This work contributes to the literature on routine dynamics by theorizing about the processes through which routine artifacts (ICTs) afforded routine participants the ability to act confidently and meaningfully to the present and dynamically coordinate their actions with their fellow routine participants

A review of solar and visible light active TiO2 photocatalysis for treating bacteria, cyanotoxins and contaminants of emerging concern

Researchintothedevelopmentofsolarandvisiblelightactivephotocatalystshasbeensignificantlyincreased\ud inrecentyearsduetoitswiderangeofapplicationsintreatingcontaminantsofemergingconcern(CECs),\ud endocrine disruptingcompounds(EDCs), bacteriaandcyanotoxins.Solarphotocatalysisisfoundtobehighly\ud effectiveintreatingawiderangeofCECsfromsourcessuchaspharmaceuticals,steroids,antibiotics,phthalates,\ud disinfectants,pesticides,fragrances(musk),preservativesandadditives.Similarly,anumberofEDCsincluding\ud polycyclicaromatichydrocarbons(PAHs),alkylphenols(APs),bisphenolA(BPA),organotins(OTs),volatileor-\ud ganic compounds(VOCs),naturalandsyntheticestrogenicandandrogenicchemicals,pesticides,andheavy\ud metalscanberemovedfromcontaminatedwaterbyusingsolarphotocatalysis.Photocatalysiswasalsofound\ud effectiveintreatingawiderangeofbacteriasuchas Staphylococcusaureus,Bacillussubtilis,Escherichiacoli,\ud Salmonellatyphi and Micrococcuslylae. Thecurrentreviewalsocomparestheeffectivenessofvariousvisible\ud lightactivatedTiO2 photocatalystsfortreatingthesepollutants. Dopingorco-dopingofTiO2 usingnitrogen,\ud nitrogen–silver,sulphur,carbon,copperandalsoincorporation ofgraphenenano-sheetsarediscussed.Theuse\ud of immobilisedTiO2 for improvingthephotocatalyticactivityisalso presented.Decoratingtitaniaphotocatalyst\ud withgrapheneoxide(GO)isofparticularinterestduetoGO'sabilitytoincreasethephotocatalyticactivityof\ud TiO2. TheuseGOtoincreasethephotocatalyticactivityofTiO2 againstmicrocystin-LR(MC-LR)underUV-Aand\ud solarirciationisdiscussed.TheenhancedphotocatalyticactivityofGO–TiO2 comparedtothecontrolmaterialis\ud attributedtotheeffectiveinhibitionoftheelectron–holerecombinationbycontrollingtheinterfacialcharge\ud transferprocess.Itisconcludedthatthereisacriticalneedforfurtherimprovementoftheefficiencyofthese\ud materialsiftheyaretobeconsideredforbulkindustrialuse

Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data

Background: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon).Results: Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent.Conclusions: Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model.Reviewers: This article was reviewed by L. Hanin, T. Radivoyevitch and L. Edler

Are the discounts in seasoned equity offers due to inelastic demand?

This paper investigates the large and diverse discounts in UK open offers and placings. Large discounts are a substantial cost to shareholders who do not buy new shares. The existing literature mainly examines US firm-commitment offers and private placements. The institutional setting differs in the UK, in ways that make the theory of inelastic demand for shares more important as an explanation for discounts than in the US. The paper finds that inelastic demand, or illiquidity of the issuer's shares, and financial distress, are key determinants of the discount. We expect these results to apply to other stock markets