Importance of heterogeneity correction for prostate therapy planning as it relates to prostate motion

2012 Fall.Includes bibliographical references.Prostate adenocarcinoma is the most common cancer among men and second leading cause of mortality of men in the United States. External beam radiotherapy (RT) is often used for local prostate tumor control as part of multimodality therapy. Dosimetric treatment planning for RT is based on complex calculations made by computerized planning software, which are designed to achieve a target prescribed dose to the prostate while not exceeding normal tissue constraints. Those RT planning calculations are made from an initial pre-treatment computed tomographic (CT) scan, which provides the location, volume and density of the prostate and critical normal tissues. The calculation step applies Heterogeneity Correction (HC) during RT planning, which adjusts the delivered radiation fields according to regional tissue densities such as the presence of bone in the anatomic region of interest. Inter-fraction and intra-fraction prostate movement are both known to occur during the course of radiotherapy. Current standards of practice utilize ways to track and account for prostatic movement in order to maintain accurate delivery to that organ. However, those methods do not adjust for the HC that was already applied during the original treatment plan calculations. The use of HC for prostate cancer RT is therefore of particular importance because prostate movement relative to the pelvic skeleton might result in dosimetric inaccuracies, since the HC used in initial RT planning is based on the original prostate position. This project was part of a larger research study in which intact normal male dogs received hypofractionated stereotactic radiation to the prostate, as a translational animal model for human prostate cancer. In this study, inter-fraction prostate motion was evaluated and then those data were used to examine the impact of this movement on the use of heterogeneity correction (HC) on stereotactic body radiation therapy (SBRT) of the prostate, by evaluating the dose received by the planned target volume (PTV) and surrounding tissue during prostate RT planning. In Aim 1, cone beam CT (CBCT) images from ten dogs were evaluated retrospectively to estimate typical inter-fraction prostate movement. Organs of interest were contoured on each daily treatment CBCT data set, and those images were registered (fused) to the original planning CT. Prostate motion was quantified by determining the displacement of each isocenter relative to the original radiotherapy planning CT. For Aim 2, CT scans acquired during the course of SBRT were used to prospectively calculate new treatment plans that incorporated prostate displacement from four dogs, with and without HC. Organs of interest were contoured on each CT data set, and images were registered (fused) to the original planning CT. As above, prostate motion was quantified by measuring the isocenter movement in three axes relative to original RT planning CT. An optimal original planning CT was run twice for each CT, with and without HC, while adjusting the prostatic isocenter. Dosimetric data for organs of interest were evaluated using dose volume histograms (DVH) and comparing doses to previously defined constraint values. Results indicated a wide range of inter-fraction prostate displacement in both Aims 1 and 2, slightly greater in magnitude than similar human prostate movement data. The greatest prostate displacement was in the y axis (anteroposterior). No statistically significant differences were seen in target or normal tissue doses, with or without HC, suggesting that even in the presence of marked prostate motion, potential inaccuracies caused by HC may not have a great impact on the prostate RT planning. As expected, without HC there was a trend for the dose to the most organs of interest to increase slightly. In terms of how displacement affected tissue doses, maximum displacement of prostate was associated with adjacent tissues exceeding the known normal tissue tolerance. In particular, caudal and left displacement led to large doses exceeding the constraint limits for the posterior rectal wall. Those data indicate the importance of continued tracking or other methods to counteract prostate motion. The results provide a more informed approach for using HC relative to prostate motion during treatment of prostate cancer, as well as providing data relevant to tumor control, acute and late toxicities associated with inter-fraction movement of prostate RT

Complete Sequences of Organelle Genomes from the Medicinal Plant Rhazya Stricta (Apocynaceae) and Contrasting Patterns of Mitochondrial Genome Evolution Across Asterids

Rhazya stricta is native to arid regions in South Asia and the Middle East and is used extensively in folk medicine to treat a wide range of diseases. In addition to generating genomic resources for this medicinally important plant, analyses of the complete plastid and mitochondrial genomes and a nuclear transcriptome from Rhazya provide insights into inter-compartmental transfers between genomes and the patterns of evolution among eight asterid mitochondrial genomes. Results: The 154,841 bp plastid genome is highly conserved with gene content and order identical to the ancestral organization of angiosperms. The 548,608 bp mitochondrial genome exhibits a number of phenomena including the presence of recombinogenic repeats that generate a multipartite organization, transferred DNA from the plastid and nuclear genomes, and bidirectional DNA transfers between the mitochondrion and the nucleus. The mitochondrial genes sdh3 and rps14 have been transferred to the nucleus and have acquired targeting presequences. In the case of rps14, two copies are present in the nucleus; only one has a mitochondrial targeting presequence and may be functional. Phylogenetic analyses of both nuclear and mitochondrial copies of rps14 across angiosperms suggests Rhazya has experienced a single transfer of this gene to the nucleus, followed by a duplication event. Furthermore, the phylogenetic distribution of gene losses and the high level of sequence divergence in targeting presequences suggest multiple, independent transfers of both sdh3 and rps14 across asterids. Comparative analyses of mitochondrial genomes of eight sequenced asterids indicates a complicated evolutionary history in this large angiosperm clade with considerable diversity in genome organization and size, repeat, gene and intron content, and amount of foreign DNA from the plastid and nuclear genomes. Conclusions: Organelle genomes of Rhazya stricta provide valuable information for improving the understanding of mitochondrial genome evolution among angiosperms. The genomic data have enabled a rigorous examination of the gene transfer events. Rhazya is unique among the eight sequenced asterids in the types of events that have shaped the evolution of its mitochondrial genome. Furthermore, the organelle genomes of R. stricta provide valuable genomic resources for utilizing this important medicinal plant in biotechnology applications.King Abdulaziz UniversityIntegrative Biolog

A game theory framework for clustering

The Game Theory-based Multi-Agent System (GTMAS) of Toreyen and Salhi, [10] and [12], implements a loosely coupled hybrid algorithm that may involve any number of algorithms suitable, a priori, for the solution of a given optimisation problem. The system allows the available algorithms to co-operate toward the solution of the problem in hand as well as compete for the computing facilities they require to run. This co-operative/competitive aspect is captured through the implementation of the Prisoners? Dilemma paradigm of game theory. Here, we apply GTMAS to the problem of clustering European Union (EU) economies, including Turkey, to find out whether the latter, based on a number of criteria, can fit in the EU and find out which countries, if any, it has strong similaries with. This clustering problem is first converted into an optimisation problem, namely the Travelling Salesman Problem (TSP) before being solved with GTMAS involving two players (agents) each implementing a standard combinatorial optimisation algorithm. Computational results are included

Electronic word of mouth in social media: The common characteristics of retweeted and favourited marketer-generated content posted on Twitter

Marketers desire to utilise electronic word of mouth (eWOM) marketing on social media sites. However, not all online content generated by marketers has the same effect on consumers; some of them are effective while others are not. This paper aims to examine different characteristics of marketer-generated content (MGC) that of which one lead users to eWOM. Twitter was chosen as one of the leading social media sites and a content analysis approach was employed to identify the common characteristics of retweeted and favourited tweets. 2,780 tweets from six companies (Booking, Hostelworld, Hotels, Lastminute, Laterooms and Priceline) operating in the tourism sector are analysed. Results indicate that the posts which contain pictures, hyperlinks, product or service information, direct answers to customers and brand centrality are more likely to be retweeted and favourited by users. The findings present the main eWOM drivers for MGC in social media.Abdulaziz Elwalda and Mohammed Alsagga

Molecular Basis of Adaptation of Enteroviruses to Different Cancer Cell Lines

Viral oncolytic therapy, a novel treatment for cancer using specially designed viruses to kill malignant cells while leaving normal cells unharmed, is currently under intense investigation. Several receptors are up-regulated in cancer cells, including decay-accelerating factor (DAF; CD55) and integrins (αvβ3, αvβ6) and viruses which recognise these receptors could be useful for therapy. Several echoviruses, including Echovirus 11 (E11), bind to DAF; coxsackievirus A9 (CVA9) utilizes an RGD motif to bind to integrins, particularly αvβ6. Some isolates of CVA9 also bind to heparan sulfate proteoglycans (HSPG). This thesis describes work designed to improve our understanding of CVA9 and echovirus cell/receptor tropism. Several echoviruses and CVA9 variants were tested in a panel of 9 cell lines. Distinct patterns of infection were seen, but did not fully correlate with receptor expression, suggesting that other determinants also help to define tropism. To investigate this further, E11 was adapted by passaging on two cell lines, A549 and HeLa. Two mutations were seen in A549-adapted virus, and both mapped to the DAF-binding footprint, suggesting changes to E11/DAF interactions. A single mutation in VP4 was seen in HeLa-adapted virus, and may affect a later stage in cell entry. To investigate CVA9 binding to HSPG, 3 isolates were propagated on A549 cells and heparin-blocked mutants were isolated. Although the isolates are diverse, the same mutation (VP3 Q59R) was seen in two isolates and probably gives a positively-charged cluster with adjacent amino acids. Other mutations were seen close to the RGD motif, where there is already a highly basic sequence. The results suggest multiple potential mechanisms for HSPG-binding. Combinations of some of the adapting mutations discovered could significantly enhance the tropism of these viruses to specific cancer cells and optimise them as oncolytic agents

Financial Inclusion in Islamic vs. Non-Islamic Countries, FinTech and Bank Competition

This thesis consists of three empirical papers on contemporary issues associated with factors that explain differences in financial inclusion. In particular the focus is on the determinants of financial inclusion and differences in account ownership according to gender, Financial Technology (FinTech) and bank competition and stability. The first empirical chapter examines the determinants of financial inclusion across Islamic and non-Islamic countries measured as differences in account ownership with a focus on gender differences from 2011 to 2017. This chapter investigates the patterns of financial inclusion and considers potential determinants of financial inclusion across five dimensions: macroeconomic, social, institutional, technological, and banking. The main findings suggest that most of our chosen determinants (non-discrimination against women, human development index, gender inequality, government integrity, mobile subscription, and individuals using the internet) are important drivers of financial inclusion across the full sample. Focusing on differences in determinants of financial inclusion across male and female account ownership in Islamic and non-Islamic countries, we find that GDP per capita positively influences male and female account ownership in non-Islamic countries. The second empirical chapter investigates the relationship between FinTech and FI using a global dataset of 46 countries over the period 2007-2019. Results demonstrate that FinTech strongly improves financial inclusion. In addition, the effects of FinTech on financial inclusion appear stronger in countries with relatively low levels of economic development, low levels of income inequality and high levels of FinTech. The third empirical chapter explores the association between financial inclusion and bank stability taking into the account the effect of bank competition. We use a sample of 241 banks in Middle East and North Africa countries (MENA) countries for the period 2012-2021. We construct a country-level index of financial inclusion using Principal Component Analysis (PCA). Our evidence illustrates a positive and significant relationship between financial inclusion and bank stability in MENA countries. Our results also suggest that high market power (measured using the Lerner index) is positively associated with bank stability. In addition, our result also indicates that bank competition only improves financial inclusion strategies that involve credit growth

High-quality permanent draft genome sequence of Bradyrhizobium sp Th.b2, a microsymbiont of Amphicarpaea bracteata collected in Johnson City, New York

Bradyrhizobium sp. Th.b2 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen-fixing root nodule of Amphicarpaea bracteata collected in Johnson City, New York. Here we describe the features of Bradyrhizobium sp. Th.b2, together with high-quality permanent draft genome sequence information and annotation. The 10,118,060 high-quality draft genome is arranged in 266 scaffolds of 274 contigs, contains 9,809 protein-coding genes and 108 RNA-only encoding genes. This rhizobial genome was sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project

High-quality permanent draft genome sequence of Bradyrhizobium sp Tv2a.2, a microsymbiont of Tachigali versicolor discovered in Barro Colorado Island of Panama

Bradyrhizobiumsp. Tv2a.2 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen-fixing root nodule of Tachigali versicolor collected in Barro Colorado Island of Panama. Here we describe the features of Bradyrhizobiumsp. Tv2a.2, together with high-quality permanent draft genome sequence information and annotation. The 8,496,279 bp high-quality draft genome is arranged in 87 scaffolds of 87 contigs, contains 8,109 protein-coding genes and 72 RNA-only encoding genes. This rhizobial genome was sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project