Search results for: cancer modelling

Authors: Congping Lin

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Intracellular transport in fungi has a number of important roles in, e.g., filamentous fungal growth and cellular metabolism. Two basic mechanisms for intracellular transport are motor-driven trafficking along microtubules (MTs) and diffusion. Mathematical modelling has been actively developed to understand such intracellular transport and provide unique insight into cellular complexity. Based on live-cell imaging data in Ustilago hyphal cells, probabilistic models have been developed to study mechanism underlying spatial organization of molecular motors and organelles. In particular, anther mechanism - stochastic motility of dynein motors along MTs has been found to contribute to half of its accumulation at hyphal tip in order to support early endosome (EE) recycling. The EE trafficking not only facilitates the directed motion of peroxisomes but also enhances their diffusive motion. Considering the importance of spatial organization of early endosomes in supporting peroxisome movement, computational and experimental approaches have been combined to a whole-cell level. Results from this interdisciplinary study promise insights into requirements for other membrane trafficking systems (e.g., in neurons), but also may inform future 'synthetic biology' studies.

Keywords: intracellular transport, stochastic process, molecular motors, spatial organization

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Authors: Aref Zribi, Sonia Ben Nasr, Sana Fendri, Mahdi Balti, Abderazzek Haddaoui

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Background: Despite their benefit, Endocrine therapies (ET) are known to have substantial adverse events (AEs) such as hot flashes, mood disorders and osteoarticular pain. ET induced alopecia(EIA) is less frequently noted by patients and is less reported in the literature. The aim of our study was to report ET alopecia characteristics and their influence on patient and treatment observance. Method: We conducted a retrospective study including luminal BC patients treated in the oncology department of the military hospital of Tunis between January 2015 and December 2020. Patients treated with previous chemotherapy-inducing alopecia were excluded. Results: 145 female patients were included. The median age was 59 years. EIA was reported in 44% of cases. Alopecia was attributed to aromatase inhibitors in 53% and tamoxifen in 21%. Severity was grade 1 in 80% and grade 2 in the remaining cases. ET discontinuation because of alopecia was noted in 6.5 % of patients. Moderate improvement of alopecia was observed with topical minoxidil and Thallium metallicum 9CH homeopathy during ET in 60% of patients. Conclusions: EIA is frequent in BC patients and should be considered to improve treatment observance and patients’ quality of life.

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Olivia A. Wilson, Hannah E. Power, Murray Kendall

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Sydney Harbour is an iconic location with a dense population and low-lying development. On the east coast of Australia, facing the Pacific Ocean, it is exposed to several tsunamigenic trenches. This paper presents a component of the most detailed assessment of the potential for earthquake-generated tsunami impact on Sydney Harbour to date. Models in this study use dynamic tides to account for tide-tsunami interaction. Sydney Harbour’s tidal range is 1.5 m, and the spring tides from January 2015 that are used in the modelling for this study are close to the full tidal range. The tsunami wave trains modelled include hypothetical tsunami generated from earthquakes of magnitude 7.5, 8.0, 8.5, and 9.0 M_W from the Puysegur and New Hebrides trenches as well as representations of the historical 1960 Chilean and 2011 Tohoku events. All wave trains are modelled for the peak wave to coincide with both a low tide and a high tide. A single wave train, representing a 9.0 M_W earthquake at the Puysegur trench, is modelled for peak waves to coincide with every hour across a 12-hour tidal phase. Using the hydrodynamic model ANUGA, results are compared according to the impact parameters of inundation area, depth variation and current speeds. Results show that both maximum inundation area and depth variation are tide dependent. Maximum inundation area increases when coincident with a higher tide, however, hazardous inundation is only observed for the larger waves modelled: NH90high and P90high. The maximum and minimum depths are deeper on higher tides and shallower on lower tides. The difference between maximum and minimum depths varies across different tidal phases although the differences are slight. Maximum current speeds are shown to be a significant hazard for Sydney Harbour; however, they do not show consistent patterns according to tide-tsunami phasing. The maximum current speed hazard is shown to be greater in specific locations such as Spit Bridge, a narrow channel with extensive marine infrastructure. The results presented for Sydney Harbour are novel, and the conclusions are consistent with previous modelling efforts in the greater area. It is shown that tide must be a consideration for both tsunami modelling and emergency management planning. Modelling with peak tsunami waves coinciding with a high tide would be a conservative approach; however, it must be considered that maximum current speeds may be higher on other tides.

Keywords: emergency management, sydney, tide-tsunami interaction, tsunami impact

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Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: DCIS accounts for 20% of malignancies diagnosed by the breast screening programme and is primarily managed by surgical excision. There is variable guidance on defining excision margins, and adjuvant treatments vary widely. This study aimed to investigate the clinical outcomes for patients following surgical excision of small volume DCIS. Methods: This single-centreretrospective cohort study of 101 consecutive breast screened patients diagnosed with DCIS who underwent surgical excision. All patients diagnosed with DCIS had radiological abnormalities <15mm. Clinical, radiological, and histological data were collected from patients who had been diagnosed within a 5 year period, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Outcomes included re-excision rates, radiotherapy usage, and the presence of invasive cancer. Results: Breast conservation surgery was performed in 94.1% (n=95). Following surgical excision, 74(73.27%)patients had complete DCIS excision (>2mm margin), 4(4.0%) had margins 1-2mm, and 17(16.84%)had margins <1mm. The median size of DCIS in the specimen sample was 4mm. In 86% of patients with involved margins (n=18), the mammogram underestimated the DCIS size by a median of 12.5mm (range: 1-42mm). Of the patients with involved margins, 11(10.9%)had a re-excision, and 6 of these (50%) required two re-excisions to completely excise the DCIS. Post-operative radiotherapy was provided to 53(52.48%)patients. Four (3.97%) patients were found to have invasive ductal carcinoma on surgical excision, which was not present on core biopsy – all had high-grade DCIS. Recurrence of DCIS was seen in the same site during follow-up in 1 patient (1%), 1 year after their first DCIS diagnosis. Conclusion: Breast conservation surgery is safe in patients with DCIS, with low rates of re-excision, recurrence, and upstaging to invasive cancer. Furthermore, the median size of DCIS found in the specimens of patients who had DCIS fully removed in surgery was low, suggesting it may be possible that total removal through VAE was possible for these patients.

Keywords: surgical excision, breast conservation surgery, DCIS, Re-excision, radiotherapy, invasive cancer

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Eric Dede, Marcus Tindall, John W. Cherrie, Steve Hankin, Christopher Collins

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Current exposure models used in contaminated land risk assessment are highly conservative. Use of these models may lead to over-estimation of actual exposures, possibly resulting in negative financial implications due to un-necessary remediation. Thus, we are carrying out a study seeking to improve our understanding of human exposure to selected toxic elements in soil: arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) resulting from allotment land-use. The study employs biomonitoring and physiologically-based pharmacokinetic (PBPK) modelling to quantify human exposure to these elements. We recruited 37 allotment users (adults > 18 years old) in Scotland, UK, to participate in the study. Concentrations of the elements (and their bioaccessibility) were measured in allotment samples (soil and allotment produce). Amount of produce consumed by the participants and participants’ biological samples (urine and blood) were collected for up to 12 consecutive months. Ethical approval was granted by the University of Reading Research Ethics Committee. PBPK models (coded in MATLAB) were used to estimate the distribution and accumulation of the elements in key body compartments, thus indicating the internal body burden. Simulating low element intake (based on estimated ‘doses’ from produce consumption records), predictive models suggested that detection of these elements in urine and blood was possible within a given period of time following exposure. This information was used in planning biomonitoring, and is currently being used in the interpretation of test results from biological samples. Evaluation of the models is being carried out using biomonitoring data, by comparing model predicted concentrations and measured biomarker concentrations. The PBPK models will be used to generate bioavailability values, which could be incorporated in contaminated land exposure models. Thus, the findings from this study will promote a more sustainable approach to contaminated land management.

Keywords: biomonitoring, exposure, PBPK modelling, toxic elements

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Authors: Aishik Deb, Rituparna Sinha

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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.

Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing

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Authors: Donghee Kang

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Background: Cancer pain is very difficult to control as the mechanism of pain is varied, and the patient has several co-morbidities. The use of Intravenous Patient-Controlled Analgesia (IV-PCA) can effectively control underlying pain and breakthrough pain. Ketamine is used in many pain patients due to its unique analgesic effect. In this study, it was checked whether there was a difference in the amount of analgesic usage, pain control degree, and side effects between patients who controlled pain with fentanyl-based IV-PCA and those who added Ketamine for pain control. Methods: Among the patients referred to this department for cancer pain, IV-PCA was applied to patients who were taking sufficient oral analgesics but could not control them or had blood clotting disorders that made the procedure difficult, and this patient group was targeted. In IV-PCA, 3000 mcg of Fentanyl, 160 mg of Nefopam, and 0.3 mg of Ramosetrone were mixed with normal saline to make a total volume of 100 ml. Group F used this IV-PCA as it is, and group K mixed 250 mg of Ketamine with normal saline to make a total volume of 100 ml. For IV-PCA, the basal rate was 0.5ml/h, the bolus was set to 1ml when pressed once, and the lockout time was set to 15 minutes. If pain was not controlled after IV-PCA application, 500 mcg of Fentanyl was added, and if excessive sedation or breathing difficulties occurred, the use was stopped for one hour. After that, the degree of daily pain control, analgesic usage, and side effects were investigated for seven days using this IV-PCA. Results: There was no difference between the two groups in the demographic data. Both groups had adequate pain control. Initial morphine milligram equivalents did not differ between the two groups, but the total amount of Fentanyl used for seven days was significantly different between the two groups [p=0.014], and group F used more Fentanyl through IV-PCA. In addition, the amount of sleeping pills used during the seven days was higher in Group F [p<0.01]. Overall, there was no difference in the frequency of side effects between the two groups, but the nausea was more frequent in Group F [p=0.031]. Discussion: When the two groups were compared, pain control was good in both groups. This seems to be because Fentanyl-based IV-PCA showed an adequate pain control effect. However, there was a significant difference in the total amount of opioid (Fentanyl) used, which is thought to be the opioid-sparing effect of Ketamine. Also, among the side effects, nausea was significantly less, which is thought to be possible because the amount of opioids used in the Ketamine group was small. The frequency of requesting sleeping pills was significantly less in the group using Ketamine, and it seems that Ketamine also helped improve sleep quality. In conclusion, using Ketamine with an opioid to control pain seems to have advantages. IV-PCA, which can be used effectively when other procedures are difficult, is more effective and safer when used together with Ketamine than opioids alone.

Keywords: cancer pain, intravenous patient-controlled analgesia, Ketamine, opioid

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Authors: Arpit Gite

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Purpose: We have evaluated the role of Total Neoadjuvant Therapy in patients with Locally Advanced Rectal cancer by giving Chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and, after that, the strategy of wait and watch. Methods: In this prospective case series, we evaluated the results of three locally advanced Rectal cancers, two cases Stage II (cT3N0) and one case Stage III ( cT4aN2). All three patients' growth was 4-6 cm from the anal verge. We have treated with Chemoradiotherapy to dose of 45Gy/25 Fractions to elective nodal regions (Inguinal node in anal canal Involvement)and Primary and mesorectum (Phase I) followed by 14.4Gy/8 Fractions to Primary and Mesorectum(Phase II) to a total dose of 59.4Gy/33 Fractions with concurrent chemotherapy Tab Capecitabine 825mg/m2 PO BD with Radiation therapy. After 6 weeks of completion of Chemoradiotherapy, advised six cycles of consolidative chemotherapy, CAPEOX regimen, Oxaliplatin 130mg/m2 on day 1 and Capecitabine 1000mg/m2 PO BD on days 1-14 repeated on a 21-day cycle for a total of six cycles. The primary endpoint is Disease-free survival (DFS); the secondary endpoint is adverse events related to chemoradiotherapy. Radiation toxicity is assessed by RTOG criteria, and chemotherapy toxicity is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: After 6 weeks of completion of Chemoradiotherapy, we did PET-CT of all three patients; all three patients had a clinically complete response and we advised 6 cycles of consolidative chemotherapy. After completion of consolidative chemotherapy, again PET-CT and sigmoidoscopy, all three patients had complete response on PET-CT and no lesions on sigmoidoscopy and kept all three patients on wait and watch.2 patients had Grade 2 skin toxicities,1 patient had Grade 1 skin toxicity, .2 patients had Grade 2 lower GI toxicities, and 1 patient had Grade lower GI toxicity, both according to RTOG criteria. 3 patients had Grade 2 diarrhea due to capecitabine, and 1 patient had Grade 1 thrombocytopenia due to oxaliplatin assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Conclusion: Sphincter Preservation is possible with this regimen in those who don’t want to opt for surgery or in case of low-lying rectal cancer.

Keywords: locally advanced rectal cancer, sphincter preservation, chemoradiotherapy, consolidative chemotherapy

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Authors: Mohammed Seyam, Faridah Othman, Ahmed El-Shafie

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The early warning of high stream flow events (HSF) and floods is an important aspect in the management of surface water and rivers systems. This process can be performed using either process-based models or data driven-based models such as artificial intelligence (AI) techniques. The main goal of this study is to develop efficient AI-based model for predicting the real-time hourly stream flow (Q) and apply it as early warning tool of HSF and floods in the downstream area of the Selangor River basin, taken here as a paradigm of humid tropical rivers in Southeast Asia. The performance of AI-based models has been improved through the integration of the lag time (Lt) estimation in the modelling process. A total of 8753 patterns of Q, water level, and rainfall hourly records representing one-year period (2011) were utilized in the modelling process. Six hydrological scenarios have been arranged through hypothetical cases of input variables to investigate how the changes in RF intensity in upstream stations can lead formation of floods. The initial SF was changed for each scenario in order to include wide range of hydrological situations in this study. The performance evaluation of the developed AI-based model shows that high correlation coefficient (R) between the observed and predicted Q is achieved. The AI-based model has been successfully employed in early warning throughout the advance detection of the hydrological conditions that could lead to formations of floods and HSF, where represented by three levels of severity (i.e., alert, warning, and danger). Based on the results of the scenarios, reaching the danger level in the downstream area required high RF intensity in at least two upstream areas. According to results of applications, it can be concluded that AI-based models are beneficial tools to the local authorities for flood control and awareness.

Keywords: floods, stream flow, hydrological modelling, hydrology, artificial intelligence

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Eun Ho Kim

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Innovations have conjured up a mode of treating GBM cancer cells in the newly diagnosed patients in a period of 4.9 months at an improved median OS, which brings along only a few minor side effects in the phase III of the clinical trial. This mode has been termed the Alternating Electric Fields (AEF). The study at hand is aimed at determining whether the AEF treatment is beneficial in sensitizing the GBM cancer cells through the process of increasing the AEF –induced senescence. The methodology to obtain the findings for this research ranged across various components, such as obtaining and testing SA-β-gal staining, flow cytometry, Western blotting, morphology, and Positron Emission Tomography (PET) / Computed Tomography (CT), immunohistochemical staining and microarray. The number of cells that displayed a senescence-specific morphology and positive SA-ß-Gal activity gradually increased up to 5 days. These results suggest that p16, p21 and p27 are essential regulators of AEF -induced senescence via NF-κB activation. The results showed that the AEF treatment is functional in enhancing the AEF –induced senescence in the GBM cells via an apoptosis- independent mechanism. This research concludes that this mode of treatment is a trustworthy protocol that can be effectively employed to overcome the limitations of the conventional mode of treatment on GBM.

Keywords: alternating electric fields, senescence, glioblastoma, cell death

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Tofigh Hamidavi, Sepehr Abrishami, Pasquale Ponterosso, David Begg

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Structural design and analysis is an important and time-consuming process, particularly at the conceptual design stage. Decisions made at this stage can have an enormous effect on the entire project, as it becomes ever costlier and more difficult to alter the choices made early on in the construction process. Hence, optimisation of the early stages of structural design can provide important efficiencies in terms of cost and time. This paper suggests a structural design optimisation (SDO) framework in which Genetic Algorithms (GAs) may be used to semi-automate the production and optimisation of early structural design alternatives. This framework has the potential to leverage conceptual structural design innovation in Architecture, Engineering and Construction (AEC) projects. Moreover, this framework improves the collaboration between the architectural stage and the structural stage. It will be shown that this SDO framework can make this achievable by generating the structural model based on the extracted data from the architectural model. At the moment, the proposed SDO framework is in the process of validation, involving the distribution of an online questionnaire among structural engineers in the UK.

Keywords: building information, modelling, BIM, genetic algorithm, GA, architecture-engineering-construction, AEC, optimisation, structure, design, population, generation, selection, mutation, crossover, offspring

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Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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Authors: Bojana Horvat, Barbara Karleusa, Goran Volf, Nevenka Ozanic, Ivica Kisic

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Forest fire is a major threat in many regions in Croatia, especially in coastal areas. Although they are often caused by natural processes, the most common cause is the human factor, intentional or unintentional. Forest fires drastically transform landscapes and influence natural processes. The main goal of the presented research is to analyse and quantify the impact of the forest fire on hydrological processes and propose the model that best describes changes in hydrological patterns in the analysed catchments. Keeping in mind the spatial component of the processes, geospatial analysis is performed to gain better insight into the spatial variability of the hydrological response to disastrous events. In that respect, two catchments that experienced severe forest fire were delineated, and various hydrological and meteorological data were collected both attribute and spatial. The major drawback is certainly the lack of hydrological data, common in small torrential karstic streams; hence modelling results should be validated with the data collected in the catchment that has similar characteristics and established hydrological monitoring. The event chosen for the modelling is the forest fire that occurred in July 2019 and burned nearly 10% of the analysed area. Surface (land use/land cover) conditions before and after the event were derived from the two Sentinel-2 images. The mapping of the burnt area is based on a comparison of the Normalized Burn Index (NBR) computed from both images. To estimate and compare hydrological behaviour before and after the event, curve number (CN) values are assigned to the land use/land cover classes derived from the satellite images. Hydrological modelling resulted in surface runoff generation and hence prediction of hydrological responses in the catchments to a forest fire event. The research was supported by the Croatian Science Foundation through the project 'Influence of Open Fires on Water and Soil Quality' (IP-2018-01-1645).

Keywords: Croatia, forest fire, geospatial analysis, hydrological response

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Omar Qaftan

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Earthquakes can cause tremendous loss of human life and can result in severe damage to a several of civil engineering structures especially the tall buildings. The response of a multistory structure subjected to earthquake loading is a complex task, and it requires to be studied by physical and numerical modelling. For many circumstances, the scale models on shaking table may be a more economical option than the similar full-scale tests. A shaking table apparatus is a powerful tool that offers a possibility of understanding the actual behaviour of structural systems under earthquake loading. It is required to use a set of scaling relations to predict the behaviour of the full-scale structure. Selecting the scale factors is the most important steps in the simulation of the prototype into the scaled model. In this paper, the principles of scaling modelling procedure are explained in details, and the simulation of scaled multi-storey concrete structure for dynamic studies is investigated. A procedure for a complete dynamic simulation analysis is investigated experimentally and numerically with a scale factor of 1/50. The frequency domain accounting and lateral displacement for both numerical and experimental scaled models are determined. The procedure allows accounting for the actual dynamic behave of actual size porotype structure and scaled model. The procedure is adapted to determine the effects of the tall multi-storey structure on a raft foundation. Four generated accelerograms were used as inputs for the time history motions which are in complying with EC8. The output results of experimental works expressed regarding displacements and accelerations are compared with those obtained from a conventional fixed-base numerical model. Four-time history was applied in both experimental and numerical models, and they concluded that the experimental has an acceptable output accuracy in compare with the numerical model output. Therefore this modelling methodology is valid and qualified for different shaking table experiments tests.

Keywords: structure, raft, soil, interaction

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Authors: Victoria Goodall, Paul Fatti, Norman Owen-Smith

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Hidden Markov Models have become popular for the analysis of animal tracking data. These models are being used to model the movements of a variety of species in many areas around the world. A common assumption of the model is that the observations need to have regular time steps. In many ecological studies, this will not be the case. The objective of the research is to modify the movement model to allow for irregularly spaced locations and investigate the effect on the inferences which can be made about the latent states. A modification of the likelihood function to allow for these irregular spaced locations is investigated, without using interpolation or averaging the movement rate. The suitability of the modification is investigated using GPS tracking data for lion (Panthera leo) in South Africa, with many observations obtained during the night, and few observations during the day. Many nocturnal predator tracking studies are set up in this way, to obtain many locations at night when the animal is most active and is difficult to observe. Few observations are obtained during the day, when the animal is expected to rest and is potentially easier to observe. Modifying the likelihood function allows the popular Hidden Markov Model framework to be used to model these irregular spaced locations, making use of all the observed data.

Keywords: hidden Markov Models, irregular observations, animal movement modelling, nocturnal predator

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Authors: Jiun-Horng Tsai, Shi-Jie, Nieh

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Fine particulate matter (PM₂.₅) has become an important issue all over the world over the last decade. Annual mean PM₂.₅ concentration has been over the ambient air quality standard of PM₂.₅ (annual average concentration as 15μg/m³) which adapted by Taiwan Environmental Protection Administration (TEPA). TEPA, therefore, has developed a number of air pollution control measures to improve the ambient concentration by reducing the emissions of primary fine particulate matter and the precursors of secondary PM₂.₅. This study investigated the potential improvement of ambient PM₂.₅ concentration by the TEPA program and the other scenario for further emission reduction on various sources. Four scenarios had been evaluated in this study, including a basic case and three reduction scenarios (A to C). The ambient PM₂.₅ concentration was evaluated by Community Multi-scale Air Quality modelling system (CMAQ) ver. 4.7.1 along with the Weather Research and Forecasting Model (WRF) ver. 3.4.1. The grid resolutions in the modelling work are 81 km × 81 km for domain 1 (covers East Asia), 27 km × 27 km for domain 2 (covers Southeast China and Taiwan), and 9 km × 9 km for domain 3 (covers Taiwan). The result of PM₂.₅ concentration simulation in different regions of Taiwan shows that the annual average concentration of basic case is 24.9 μg/m³, and are 22.6, 18.8, and 11.3 μg/m³, respectively, for scenarios A to C. The annual average concentration of PM₂.₅ would be reduced by 9-55 % for those control scenarios. The result of scenario C (the emissions of precursors reduce to allowance levels) could improve effectively the airborne PM₂.₅ concentration to attain the air quality standard. According to the results of unit precursor reduction contribution, the allowance emissions of PM₂.₅, SOₓ, and NOₓ are 16.8, 39, and 62 thousand tons per year, respectively. In the Kao-Ping air basin, the priority for reducing precursor emissions is PM₂.₅ > NOₓ > SOₓ, whereas the priority for reducing precursor emissions is PM₂.₅ > SOₓ > NOₓ in others area. The result indicates that the target pollutants that need to be reduced in different air basin are different, and the control measures need to be adapted to local conditions.

Keywords: airborne PM₂.₅, community multi-scale air quality modelling system, control measures, weather research and forecasting model

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Authors: Amenah Dhannoon, Ciaran Martin Hurley, Laura Wrafter, Podraic J. Regan

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Introduction: The COVID-19 pandemic continues to present unprecedented challenges for healthcare systems. This has resulted in the pragmatic shift in the practice of plastic surgery units worldwide. During this period, many units reported a significant fall in urgent melanoma referrals, leading to patients presenting with advanced disease requiring more extensive surgery and inferior outcomes. Our objective was to evaluate our unit's experience with both non-invasive and invasive melanoma during the COVID-19 pandemic and characterize our experience and contrast it to that experienced by our neighbors in the UK, mainland Europe and North America. Methods: a retrospective chart review was performed on all patients diagnosed with invasive and non-invasive cutaneous melanoma between March to December of 2019 (control) compared to 2020 (COVID-19 pandemic) in a single plastic surgery unit in Ireland. Patient demographics, referral source, surgical procedures, tumour characteristics, radiological findings, oncological therapies and follow-up were recorded. All data were anonymized and stored in Microsoft Excel. Results: A total of 589 patients were included in the study. Of these, 314 (53%) with invasive melanoma, compared to 275 (47%) with the non-invasive disease. Overall, more patients were diagnosed with both invasive and non-invasive melanoma in 2020 than in 2019 (p<0.05). However, significantly longer waiting times in 2020 (64 days) compared to 2019 (28 days) (p<0.05), with the majority of the referral being from GP in 2019 (83%) compared to 61% in 2020. Positive sentinel lymph node were higher in 2019 at 56% (n=28) compared to 24% (n=22) in 2020. There was no statistically significant difference in the tutor characteristics or metastasis status. Discussion: While other countries have noticed a fall in the melanoma diagnosis. Our units experienced a higher number of disease diagnoses. This can be due to multiple reasons. In Ireland, the government reached an early agreement with the private sector to continue elective surgery on an urgent basis in private hospitals. This allowed access to local anesthetic procedures and local skin cancer cases were triaged to non-COVID-19 provider centers. Our unit also adapted a fast, effective and minimal patient contact strategy for triaging skin cancer based on telemedicine. Thirdly, a skin cancer nurse specialist maintained patient follow-ups and triaging a dedicated email service. Finally, our plastic surgery service continued to maintain a virtual complex skin cancer multidisciplinary team meeting during the pandemic, ensuring local clinical governance has adhered to each clinical case. Conclusion: Our study highlights that with the prompt efficient restructuring of services, we could reserve successful management of skin cancer even in the most devastating times. It is important to reflect on the success during the pandemic and emphasize the importance of preparation for a potentially difficult future

Keywords: malignant melanoma, skin cancer, COVID-19, triage

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Wassana Naiyapo, Atichat Sangtong

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The processes in software development by Object Oriented methodology have many stages those take time and high cost. The inconceivable error in system analysis process will affect to the design and the implementation process. The unexpected output causes the reason why we need to revise the previous process. The more rollback of each process takes more expense and delayed time. Therefore, the good test process from the early phase, the implemented software is efficient, reliable and also meet the user’s requirement. Unified Modelling Language (UML) is the tool which uses symbols to describe the work process in Object Oriented Analysis (OOA). This paper presents the approach for automatically generated UML use case diagram and test cases. UML use case diagram is generated from the event table and test cases are generated from use case specifications and Graphic User Interfaces (GUI). Test cases are derived from the Classification Tree Method (CTM) that classify data to a node present in the hierarchy structure. Moreover, this paper refers to the program that generates use case diagram and test cases. As the result, it can reduce work time and increase efficiency work.

Keywords: classification tree method, test case, UML use case diagram, use case specification

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Authors: Mohammed Salahat, Steve Wade

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This paper presents and compares the SSDDD “Systematic Soft Domain Driven Design Framework” to DDD “Domain Driven Design Framework” as a soft system approach of information systems development. The framework use SSM as a guiding methodology within which we have embedded a sequence of design tasks based on the UML leading to the implementation of a software system using the Naked Objects framework. This framework has been used in action research projects that have involved the investigation and modelling of business processes using object-oriented domain models and the implementation of software systems based on those domain models. Within this framework, Soft Systems Methodology (SSM) is used as a guiding methodology to explore the problem situation and to develop the domain model using UML for the given business domain. The framework is proposed and evaluated in our previous works, a comparison between SSDDD and DDD is presented in this paper, to show how SSDDD improved DDD as an approach to modelling and implementing business domain perspectives for Information Systems Development. The comparison process, the results, and the improvements are presented in the following sections of this paper.

Keywords: domain-driven design, soft domain-driven design, naked objects, soft language

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Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat

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Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.

Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma

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Authors: Cheng Zhang, James Marco, Walid Allafi, Truong Q. Dinh, W. D. Widanage

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Equivalent circuit models (ECMs) are widely used in battery management systems in electric vehicles and other battery energy storage systems. The battery dynamics and the model parameters vary under different working conditions, such as different temperature and state of charge (SOC) levels, and therefore online parameter identification can improve the modelling accuracy. This paper presents a way of online ECM parameter identification using a continuous time (CT) estimation method. The CT estimation method has several advantages over discrete time (DT) estimation methods for ECM parameter identification due to the widely separated battery dynamic modes and fast sampling. The presented method can be used for online SOC estimation. Test data are collected using a lithium ion cell, and the experimental results show that the presented CT method achieves better modelling accuracy compared with the conventional DT recursive least square method. The effectiveness of the presented method for online SOC estimation is also verified on test data.

Keywords: electric circuit model, continuous time domain estimation, linear integral filter method, parameter and SOC estimation, recursive least square

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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Authors: Nor Mazlin Zahari, Lian Gan, Xuerui Mao

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The power production in wind farms and the mechanical loads on the turbines are strongly impacted by the wake of the wind turbine. Thus, there is a need for understanding and modelling the turbine wake dynamic in the wind farm and the layout optimization. Having a good wake model is important in predicting plant performance and understanding fatigue loads. In this paper, the Dynamic Mode Decomposition (DMD) was applied to the simulation data generated by a Direct Numerical Simulation (DNS) of flow around a turbine, perturbed by upstream inflow noise. This technique is useful in analyzing the wake flow, to predict its future states and to reflect flow dynamics associated with the coherent structures behind wind turbine wake flow. DMD was employed to describe the dynamic of the flow around turbine from the DNS data. Since the DNS data comes with the unstructured meshes and non-uniform grid, the interpolation of each occurring within each element in the data to obtain an evenly spaced mesh was performed before the DMD was applied. DMD analyses were able to tell us characteristics of the travelling waves behind the turbine, e.g. the dominant helical flow structures and the corresponding frequencies. As the result, the dominant frequency will be detected, and the associated spatial structure will be identified. The dynamic mode which represented the coherent structure will be presented.

Keywords: coherent structure, Direct Numerical Simulation (DNS), dominant frequency, Dynamic Mode Decomposition (DMD)

Procedia PDF Downloads 335