Intensity-modulated radiotherapy for prostate cancer

Radiation therapy (RT) is a curative treatment modality for localized prostate cancer. Over the past two decades, advances in technology and imaging have considerably changed RT in prostate cancer treatment. Treatment has evolved from 2-dimensional (2D) planning using X-ray fields based on pelvic bony landmarks to 3-dimensional (3D) conformal RT (CRT) which uses computed tomography (CT) based planning. Despite improvements with 3D-CRT, dose distributions often remained suboptimal with portions of the rectum and bladder receiving unacceptably high doses. In more recent years, intensity-modulated radiation therapy (IMRT) has become the standard of care to deliver external beam RT. IMRT uses multiple radiation beams of different shapes and intensities delivered from a wide range of angles to \u27paint\u27 the radiation dose onto the tumor. IMRT allows for a higher dose of radiation to be delivered to the prostate while reducing dose to surrounding organs. Multiple clinical trials have demonstrated improved cancer outcomes with dose escalation, but toxicities using 3D-CRT and escalated doses have been problematic. IMRT is a method to deliver dose escalated RT with more conformal dose distributions than 3D-CRT and has been associated with improved toxicity profiles. IMRT also appears to be the safest method to deliver hypofractionated RT and pelvic lymph node radiation. The purpose of this review is to summarize the technical aspects of IMRT planning and delivery, and to review the literature supporting the use of IMRT for prostate cancer

Multiparametric MRI and [18F]fluorodeoxyglucose positron emission tomography imaging is a potential prognostic imaging biomarker in recurrent glioblastoma

Purpose/objectivesMultiparametric advanced MR and [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging may be important biomarkers for prognosis as well for distinguishing recurrent glioblastoma multiforme (GBM) from treatment-related changes.Methods/materialsWe retrospectively evaluated 30 patients treated with chemoradiation for GBM and underwent advanced MR and FDG-PET for confirmation of tumor progression. Multiparametric MRI and FDG-PET imaging metrics were evaluated for their association with 6-month overall (OS) and progression-free survival (PFS) based on pathological, radiographic, and clinical criteria.Results17 males and 13 females were treated between 2001 and 2014, and later underwent FDG-PET at suspected recurrence. Baseline FDG-PET and MRI imaging was obtained at a median of 7.5 months [interquartile range (IQR) 3.7–12.4] following completion of chemoradiation. Median follow-up after FDG-PET imaging was 10 months (IQR 7.2–13.0). Receiver-operator characteristic curve analysis identified that lesions characterized by a ratio of the SUVmax to the normal contralateral brain (SUVmax/NB index) >1.5 and mean apparent diffusion coefficient (ADC) value of ≤1,400 × 10−6 mm2/s correlated with worse 6-month OS and PFS. We defined three patient groups that predicted the probability of tumor progression: SUVmax/NB index >1.5 and ADC ≤1,400 × 10−6 mm2/s defined high-risk patients (n = 7), SUVmax/NB index ≤1.5 and ADC >1,400 × 10−6 mm2/s defined low-risk patients (n = 11), and intermediate-risk (n = 12) defined the remainder of the patients. Median OS following the time of the FDG-PET scan for the low, intermediate, and high-risk groups were 23.5, 10.5, and 3.8 months (p < 0.01). Median PFS were 10.0, 4.4, and 1.9 months (p = 0.03). Rates of progression at 6-months in the low, intermediate, and high-risk groups were 36, 67, and 86% (p = 0.04).ConclusionRecurrent GBM in the molecular era is associated with highly variable outcomes. Multiparametric MR and FDG-PET biomarkers may provide a clinically relevant, non-invasive and cost-effective method of predicting prognosis and improving clinical decision making in the treatment of patients with suspected tumor recurrence

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73 m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73 m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria

Rational Passivation of Sulfur Vacancy Defects in Two-Dimensional Transition Metal Dichalcogenides.

Structural defects vary the optoelectronic properties of monolayer transition metal dichalcogenides, leading to concerted efforts to control defect type and density via materials growth or postgrowth passivation. Here, we explore a simple chemical treatment that allows on-off switching of low-lying, defect-localized exciton states, leading to tunable emission properties. Using steady-state and ultrafast optical spectroscopy, supported by ab initio calculations, we show that passivation of sulfur vacancy defects, which act as exciton traps in monolayer MoS2 and WS2, allows for controllable and improved mobilities and an increase in photoluminescence up to 275-fold, more than twice the value achieved by other chemical treatments. Our findings suggest a route for simple and rational defect engineering strategies for tunable and switchable electronic and excitonic properties through passivation

Rational Passivation of Sulfur Vacancy Defects in Two-Dimensional Transition Metal Dichalcogenides.

Structural defects vary the optoelectronic properties of monolayer transition metal dichalcogenides, leading to concerted efforts to control defect type and density via materials growth or postgrowth passivation. Here, we explore a simple chemical treatment that allows on-off switching of low-lying, defect-localized exciton states, leading to tunable emission properties. Using steady-state and ultrafast optical spectroscopy, supported by ab initio calculations, we show that passivation of sulfur vacancy defects, which act as exciton traps in monolayer MoS2 and WS2, allows for controllable and improved mobilities and an increase in photoluminescence up to 275-fold, more than twice the value achieved by other chemical treatments. Our findings suggest a route for simple and rational defect engineering strategies for tunable and switchable electronic and excitonic properties through passivation

Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in Mycobacteria

Background. Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. Methodology/Principle Findings. We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strainMycobacterium bovis BCG, as well as in the related pathogenic speciesMycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified fromdrug-treated mycobacteria showed a significant loss of cyclopropanation in both the a- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclopropanation, suggesting that the drugs act directly on CMASs. Conclusions/Significance. This is a first report on them echanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment

Proceedings of Abstracts Engineering and Computer Science Research Conference 2019

© 2019 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Note: Keynote: Fluorescence visualisation to evaluate effectiveness of personal protective equipment for infection control is © 2019 Crown copyright and so is licensed under the Open Government Licence v3.0. Under this licence users are permitted to copy, publish, distribute and transmit the Information; adapt the Information; exploit the Information commercially and non-commercially for example, by combining it with other Information, or by including it in your own product or application. Where you do any of the above you must acknowledge the source of the Information in your product or application by including or linking to any attribution statement specified by the Information Provider(s) and, where possible, provide a link to this licence: http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/This book is the record of abstracts submitted and accepted for presentation at the Inaugural Engineering and Computer Science Research Conference held 17th April 2019 at the University of Hertfordshire, Hatfield, UK. This conference is a local event aiming at bringing together the research students, staff and eminent external guests to celebrate Engineering and Computer Science Research at the University of Hertfordshire. The ECS Research Conference aims to showcase the broad landscape of research taking place in the School of Engineering and Computer Science. The 2019 conference was articulated around three topical cross-disciplinary themes: Make and Preserve the Future; Connect the People and Cities; and Protect and Care

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.