Search results for: cluster head
Commenced in January 2007
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Edition: International
Paper Count: 1701

Search results for: cluster head

1401 A New Complex Method for Integrated Warehouse Design in Aspect of Dynamic and Static Capacity

Authors: Tamas Hartvanyi, Zoltan Andras Nagy, Miklos Szabo

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The dynamic and static capacity are two opposing aspect of warehouse design. Static capacity optimization aims to maximize the space-usage for goods storing, while dynamic capacity needs more free place to handling them. They are opposing by the building structure and the area utilization. According to Pareto principle: the 80% of the goods are the 20% of the variety. From the origin of this statement, it worth to store the big amount of same products by fulfill the space with minimal corridors, meanwhile the rest 20% of goods have the 80% variety of the whole range, so there is more important to be fast-reachable instead of the space utilizing, what makes the space fulfillment numbers worse. The warehouse design decisions made in present practice by intuitive and empiric impressions, the planning method is formed to one selected technology, making this way the structure of the warehouse homogeny. Of course the result can’t be optimal for the inhomogeneous demands. A new innovative model based on our research will be introduced in this paper to describe the technic capacities, what makes possible to define optimal cluster of technology. It is able to optimize the space fulfillment and the dynamic operation together with this cluster application.

Keywords: warehouse, warehouse capacity, warehouse design method, warehouse optimization

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1400 Selecting a Material for an Aircraft Diesel Engine Block

Authors: Ksenia Siadkowska, Tytus Tulwin, Rafał Sochaczewski

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Selecting appropriate materials is presently a complex task as material databases cover tens of thousands of different types of materials. Product designing proceeds in numerous stages and in most of them there are open questions with not only one correct solution but better and worse ones. This paper overviews the Diesel engine body construction materials mentioned in the literature and discusses a certain practical method to select materials for a cylinder head and a Diesel engine block as a prototype. The engine body, depending on its purpose, is most frequently iron or aluminum. If it is important to optimize parts to achieve low weight, aluminum alloys are usually applied, especially in the automotive and aviation industries. In the latter case, weight is even more important so new types of magnesium alloys which are even lighter than aluminum ones are developed and used. However, magnesium alloys are, for example, more flammable and not enough strong so, for safety reasons, this type of material is not used solely in engine bodies. Acknowledgement: This work has been realized in the cooperation with The Construction Office of WSK "PZL-KALISZ" S.A." and is part of Grant Agreement No. POIR.01.02.00-00-0002/15 financed by the Polish National Centre for Research and Development.

Keywords: aluminum alloy, cylinder head, Diesel engine, materials selection

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1399 One Year Follow up of Head and Neck Paragangliomas: A Single Center Experience

Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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1398 Formulation and Evaluation of Metformin Hydrochloride Microparticles via BÜCHI Nano-Spray Dryer B-90

Authors: Tamer Shehata

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Recently, nanotechnology acquired a great interest in the field of pharmaceutical production. Several pharmaceutical equipment were introduced into the research field for production of nanoparticles, among them, BÜCHI’ fourth generation nano-spray dryer B-90. B-90 is specialized with single step of production and drying of nano and microparticles. Currently, our research group is investigating several pharmaceutical formulations utilizing BÜCHI Nano-Spray Dryer B-90 technology. One of our projects is the formulation and evaluation of metformin hydrochloride mucoadhesive microparticles for treatment of type 2-diabetis. Several polymers were investigated, among them, gelatin and sodium alginate. The previous polymers are natural polymers with mucoadhesive properties. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension were performed. Postformulation characters such as particle size, flowability, surface scan and dissolution profile were evaluated. Finally, the pharmacological activity of certain selected formula was evaluated in streptozotocin-induced diabetic rats. B-90’spray head was 7 µm hole heated to 120 with air flow rate 3.5 mL/min. The viscosity of the solution was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Successfully, discrete, non-aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and Sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, mucoadhesive metformin hydrochloride microparticles obtained from B-90 could offer a convenient dosage form with enhanced hypoglycemic activity.

Keywords: mucoadhesive, microparticles, metformin hydrochloride, nano-spray dryer

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1397 Association of Maternal Diet Quality Indices and Dietary Patterns during Lactation and the Growth of Exclusive Breastfed Infant

Authors: Leila Azadbakht, Maedeh Moradi, Mohammad Reza Merasi, Farzaneh Jahangir

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Maternal dietary intake during lactation might affect the growth rate of an exclusive breastfed infant. The present study was conducted to evaluate the effect of maternal dietary patterns and quality during lactation on the growth of the exclusive breastfed infant. Methods: 484 healthy lactating mothers with their infant were enrolled in this study. Only exclusive breastfed infants were included in this study which was conducted in Iran. Dietary intake of lactating mothers was assessed using a validated and reliable semi-quantitative food frequency questionnaire. Diet quality indices such as alternative Healthy eating index (HEI), Dietary energy density (DED), and adherence to Mediterranean dietary pattern score, Nordic and dietary approaches to stop hypertension (DASH) eating pattern were created. Anthropometric features of infant (weight, height, and head circumference) were recorded at birth, two and four months. Results: Weight, length, weight for height and head circumference of infants at two months and four months age were mostly in the normal range among those that mothers adhered more to the HEI in lactation period (normal weight: 61%; normal height: 59%). The prevalence of stunting at four months of age among those whose mothers adhered more to the HEI was 31% lower than those with the least adherence to HEI. Mothers in the top tertiles of HEI score had the lowest frequency of having underweight infants (18% vs. 33%; P=0.03). Odds ratio of being overweight or obese at four months age was the lowest among those infants whose mothers adhered more to the HEI (OR: 0.67 vs 0.91; Ptrend=0.03). However, there was not any significant association between adherence of mothers to Mediterranean diet as well as DASH diet and Nordic eating pattern and the growth of infants (none of weight, height or head circumference). Infant weight, length, weight for height and head circumference at two months and four months did not show significant differences among different tertile categories of mothers’ DED. Conclusions: Higher diet quality indices and more adherence of lactating mother to HEI (as an indicator of diet quality) may be associated with better growth indices of the breastfed infant. However, it seems that DED of the lactating mother does not affect the growth of the breastfed infant. Adherence to the different dietary patterns such as Mediterranean, DASH or Nordic among mothers had no different effect on the growth indices of the infants. However, higher diet quality indices and more adherence of lactating mother to HEI may be associated with better growth indices of the breastfed infant. Breastfeeding is a complete way that is not affected much by the dietary patterns of the mother. However, better diet quality might be associated with better growth.

Keywords: breastfeeding, growth, infant, maternal diet

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1396 Phylogenetic Studies of Six Egyptian Sheep Breeds Using Cytochrome B

Authors: Othman Elmahdy Othman, Agnés Germot, Daniel Petit, Muhammad Khodary, Abderrahman Maftah

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Recently, the control (D-loop) and cytochrome b (Cyt b) regions of mtDNA have received more attention due to their role in the genetic diversity and phylogenetic studies in different livestock which give important knowledge towards the genetic resource conservation. Studies based on sequencing of sheep mitochondrial DNA showed that there are five maternal lineages in the world for domestic sheep breeds; A, B, C, D and E. By using cytochrome B sequencing, we aimed to clarify the genetic affinities and phylogeny of six Egyptian sheep breeds. Blood samples were collected from 111 animals belonging to six Egyptian sheep breeds; Barki, Rahmani, Ossimi, Saidi, Sohagi and Fallahi. The total DNA was extracted and the specific primers were used for conventional PCR amplification of the cytochrome B region of mtDNA. PCR amplified products were purified and sequenced. The alignment of sequences was done using BioEdit software and DnaSP 5.00 software was used to identify the sequence variation and polymorphic sites in the aligned sequences. The result showed that the presence of 39 polymorphic sites leading to the formation of 29 haplotypes. The haplotype diversity in six tested breeds ranged from 0.643 in Rahmani breed to 0.871 in Barki breed. The lowest genetic distance was observed between Rahmani and Saidi (D: 1.436 and Dxy: 0.00127) while the highest distance was observed between Ossimi and Sohagi (D: 6.050 and Dxy: 0.00534). Neighbour-joining (Phylogeny) tree was constructed using Mega 5.0 software. The sequences of 111 analyzed samples were aligned with references sequences of different haplogroups; A, B, C, D and E. The phylogeny result showed the presence of four haplogroups; HapA, HapB, HapC and HapE in the examined samples whereas the haplogroup D was not found. The result showed that 88 out of 111 tested animals cluster with haplogroup B (79.28%), whereas 12 tested animals cluster with haplogroup A (10.81%), 10 animals cluster with haplogroup C (9.01%) and one animal belongs to haplogroup E (0.90%).

Keywords: phylogeny, genetic biodiversity, MtDNA, cytochrome B, Egyptian sheep

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1395 Development of Swing Valve for Gasoline Turbocharger Using Hybrid Metal Injection Molding

Authors: B. S. So, Y. H. Yoon, J. O. Jung, K. S. Bae

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Metal Injection Molding (MIM) is a technology that combines powder metallurgy and injection molding. Particularly, it is widely applied to the manufacture of precision mobile parts and automobile turbocharger parts because compact precision parts with complicated three-dimensional shapes that are difficult to machining are formed into a large number of finished products. The swing valve is a valve that adjusts the boost pressure of the turbocharger. Since the head portion is exposed to the harsh temperature condition of about 900 degrees in the gasoline GDI engine, it is necessary to use Inconel material with excellent heat resistance and abrasion resistance, resulting in high manufacturing cost. In this study, we developed a swing valve using a metal powder injection molding based hybrid material (Inconel 713C material with heat resistance is applied to the head part, and HK30 material with low price is applied to the rest of the body part). For this purpose, the process conditions of the metal injection molding were optimized to minimize the internal defects, and the effectiveness was confirmed by the fracture strength and fatigue test.

Keywords: hybrid metal injection molding, swing valve, turbocharger, double injection

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1394 The Algorithm of Semi-Automatic Thai Spoonerism Words for Bi-Syllable

Authors: Nutthapat Kaewrattanapat, Wannarat Bunchongkien

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The purposes of this research are to study and develop the algorithm of Thai spoonerism words by semi-automatic computer programs, that is to say, in part of data input, syllables are already separated and in part of spoonerism, the developed algorithm is utilized, which can establish rules and mechanisms in Thai spoonerism words for bi-syllables by utilizing analysis in elements of the syllables, namely cluster consonant, vowel, intonation mark and final consonant. From the study, it is found that bi-syllable Thai spoonerism has 1 case of spoonerism mechanism, namely transposition in value of vowel, intonation mark and consonant of both 2 syllables but keeping consonant value and cluster word (if any). From the study, the rules and mechanisms in Thai spoonerism word were applied to develop as Thai spoonerism word software, utilizing PHP program. the software was brought to conduct a performance test on software execution; it is found that the program performs bi-syllable Thai spoonerism correctly or 99% of all words used in the test and found faults on the program at 1% as the words obtained from spoonerism may not be spelling in conformity with Thai grammar and the answer in Thai spoonerism could be more than 1 answer.

Keywords: algorithm, spoonerism, computational linguistics, Thai spoonerism

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1393 Accidents Involving Pedestrians Walking along with/against Traffic: An Evaluation of Crash Characteristics and Injuries

Authors: Chih-Wei Pai, Rong-Chang Jou

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Using A1 A2 police-reported accident data for years 2003–2010 in Taiwan, the paper examines anatomic injuries and crash characteristics specific to pedestrians in “facing traffic” and “back to traffic” crashes. There were 2768 and 7558 accidents involving pedestrians walking along with/against traffic respectively. Injuries sustained by pedestrians and crash characteristics in these two crash types were compared with those in other crash types (nearside crash, nearside dart-out crash, offside crash, offside dart-out crash). Main findings include that “back to traffic” crashes resulted in more severe injuries, and pedestrians in “back to traffic” crashes had increased head, neck, and spine injuries than those in other crash types; and there was an elevated risk of head injuries in unlit darkness and NBU (non-built-up) roadways. Several crash features (e.g. unlit darkness, overtaking maneuvers, phone use by pedestrians and drivers, intoxicated drivers) appear to be over-involved in “back to traffic” crashes. The implications of the research findings regarding pedestrian/driver education, enforcement, and remedial engineering design are discussed.

Keywords: pedestrian accident, crash characteristics, injury, facing traffic, back to traffic

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1392 Development of Extruded Prawn Snack Using Prawn Flavor Powder from Prawn Head Waste

Authors: S. K. Sharma, P. Kumar, Pratibha Singh

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Consumption of SNACK is growing its popularity every day in India and a broad range of these items are available in the market. The end user interest in ready-to-eat snack foods is constantly growing mainly due to their ease, ample accessibility, appearance, taste and texture. Food extrusion has been practiced for over fifty years. Its role was initially limited to mixing and forming cereal products. Although thermoplastic extrusion has been successful for starch products, extrusion of proteins has achieved only limited success. In this study, value-added extruded prawn product was prepared with prawn flavor powder and corn flour using a twin-screw extruder. Prawn flavor concentrates prepared from fresh prawn head (Solenocera indica). To prepare flavor concentrate prawn head washed with potable water and blended with 200ml 3% salt solution per 250gm head weight to make the slurry, which was further put in muslin cloth and boiled with salt and starch solution for 10 minutes, cooled to room temperature and filtered, starch added to the filtrate and made into powder in an electrically drier at 43-450c. The mixture was passed through the twin-screw extruder (co-rotating twin screw extruder - basic technology Pvt. Ltd., Kolkata) which was operated at a particular speed of rotation, die diameter, temperature, moisture, and fish powder concentration. Many trial runs were conducted to set up the process variables. The different extrudes produced after each trail were examined for the quality and characteristics. The effect of temperature, moisture, screw speed, protein, fat, ash and thiobarbituric acid (TBA) number and expansion ratio were studied. In all the four trials, moisture, temperature, speed and die diameter used was 20%, 100°C, 350 rpm and 4 mm, respectively. The ratio of prawn powder and cornstarch used in different trials ranged between 2:98 and 10:90. The storage characteristics of the final product were studied using three different types of packaging under nitrogen flushing, i.e. a- 12-pm polyester, 12-pm metalized polyester, 60-11m polyethylene (metalized polyester a), b- 12-11m metalized polyester, 37.5-11m polyethylene (metalized polyester b), c- 12-11m polyethylene, 9-11m aluminium foil, 37.5-11m polyethylene (aluminium foil). The organoleptic analysis was carried out on a 9-point hedonic scale. The study revealed that the fried product packed in aluminum foil under nitrogen flushing would remain acceptable for more than three months.

Keywords: extruded product, prawn flavor, twin-screw extruder, storage characteristics

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1391 An Approach for Estimation in Hierarchical Clustered Data Applicable to Rare Diseases

Authors: Daniel C. Bonzo

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Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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1390 Application of Decline Curve Analysis to Depleted Wells in a Cluster and then Predicting the Performance of Currently Flowing Wells

Authors: Satish Kumar Pappu

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The most common questions which are frequently asked in oil and gas industry are how much is the current production rate from a particular well and what is the approximate predicted life of that well. These questions can be answered through forecasting of important realistic data like flowing tubing hole pressures FTHP, Production decline curves which are used predict the future performance of a well in a reservoir. With the advent of directional drilling, cluster well drilling has gained much importance and in-fact has even revolutionized the whole world of oil and gas industry. An oil or gas reservoir can generally be described as a collection of several overlying, producing and potentially producing sands in to which a number of wells are drilled depending upon the in-place volume and several other important factors both technical and economical in nature, in some sands only one well is drilled and in some, more than one. The aim of this study is to derive important information from the data collected over a period of time at regular intervals on a depleted well in a reservoir sand and apply this information to predict the performance of other wells in that reservoir sand. The depleted wells are the most common observations when an oil or gas field is being visited, w the application of this study more realistic in nature.

Keywords: decline curve analysis, estimation of future gas reserves, reservoir sands, reservoir risk profile

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1389 Barclays Bank Zambia: Considerations for Raft Foundation Design on Dolomite Land

Authors: Yashved Serhun, Kim A. Timm

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Barclays Bank has identified the need for a head office building in Lusaka, Zambia, and construction of a 7200 m2 three-storey reinforced concrete office building with a structural steel roof is currently underway. A unique characteristic of the development is that the building footprint is positioned on dolomitic land. Dolomite rock has the tendency to react with and breakdown in the presence of slightly acidic water, including rainwater. This leads to a potential for subsidence and sinkhole formation. Subsidence and the formation of sinkholes beneath a building can be detrimental during both the construction and operational phases. This paper outlines engineering principles which were considered during the structural design of the raft foundation for the Barclays head office building. In addition, this paper includes multidisciplinary considerations and the impact of these on the structural engineering design of the raft foundation. By ensuring that the design of raft foundations on dolomitic land incorporates the requirements of all disciplines and relevant design codes during the design process, the risk associated with subsidence and sinkhole formation can be effectively mitigated during the operational phase of the building.

Keywords: dolomite, dolomitic land, raft foundation, structural engineering design

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1388 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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1387 A Study on the Relation among Primary Care Professionals Serving Disadvantaged Community, Socioeconomic Status, and Adverse Health Outcome

Authors: Chau-Kuang Chen, Juanita Buford, Colette Davis, Raisha Allen, John Hughes, James Tyus, Dexter Samuels

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During the post-Civil War era, the city of Nashville, Tennessee, had the highest mortality rate in the country. The elevated death and disease among ex-slaves were attributable to the unavailability of healthcare. To address the paucity of healthcare services, the College, an institution with the mission of educating minority professionals and serving the under served population, was established in 1876. This study was designed to assess if the College has accomplished its mission of serving under served communities and contributed to the elimination of health disparities in the United States. The study objective was to quantify the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities, which, in turn, was significantly associated with a health professional shortage score partly designated by the U.S. Department of Health and Human Services. Various statistical methods were used to analyze the alumni data in years 1975 – 2013. K-means cluster analysis was utilized to identify individual medical and dental graduates into the cluster groups of the practice communities (Disadvantaged or Non-disadvantaged Communities). Discriminant analysis was implemented to verify the classification accuracy of cluster analysis. The independent t test was performed to detect the significant mean differences for clustering and criterion variables between Disadvantaged and Non-disadvantaged Communities, which confirms the “content” validity of cluster analysis model. Chi-square test was used to assess if the proportion of cluster groups (Disadvantaged vs Non-disadvantaged Communities) were consistent with that of practicing specialties (primary care vs. non-primary care). Finally, the partial least squares (PLS) path model was constructed to explore the “construct” validity of analytics model by providing the magnitude effects of socioeconomic status and adverse health outcome on primary care professionals serving disadvantaged community. The social ecological theory along with statistical models mentioned was used to establish the relationship between medical and dental graduates (primary care professionals serving disadvantaged communities) and their social environments (socioeconomic status, adverse health outcome, health professional shortage score). Based on social ecological framework, it was hypothesized that the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities could be quantified. Also, primary care professionals serving disadvantaged communities related to a health professional shortage score can be measured. Adverse health outcome (adult obesity rate, age-adjusted premature mortality rate, and percent of people diagnosed with diabetes) could be affected by the latent variable, namely socioeconomic status (unemployment rate, poverty rate, percent of children who were in free lunch programs, and percent of uninsured adults). The study results indicated that approximately 83% (3,192/3,864) of the College’s medical and dental graduates from 1975 to 2013 were practicing in disadvantaged communities. In addition, the PLS path modeling demonstrated that primary care professionals serving disadvantaged community was significantly associated with socioeconomic status and adverse health outcome (p < .001). In summary, the majority of medical and dental graduates from the College provide primary care services to disadvantaged communities with low socioeconomic status and high adverse health outcomes, which demonstrate that the College has fulfilled its mission.

Keywords: disadvantaged community, K-means cluster analysis, PLS path modeling, primary care

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1386 Disclosure on Adherence of the King Code's Audit Committee Guidance: Cluster Analyses to Determine Strengths and Weaknesses

Authors: Philna Coetzee, Clara Msiza

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In modern society, audit committees are seen as the custodians of accountability and the conscience of management and the board. But who holds the audit committee accountable for their actions or non-actions and how do we know what they are supposed to be doing and what they are doing? The purpose of this article is to provide greater insight into the latter part of this problem, namely, determine what best practises for audit committees and the disclosure of what is the realities are. In countries where governance is well established, the roles and responsibilities of the audit committee are mostly clearly guided by legislation and/or guidance documents, with countries increasingly providing guidance on this topic. With high cost involved to adhere to governance guidelines, the public (for public organisations) and shareholders (for private organisations) expect to see the value of their ‘investment’. For audit committees, the dividends on the investment should reflect in less fraudulent activities, less corruption, higher efficiency and effectiveness, improved social and environmental impact, and increased profits, to name a few. If this is not the case (which is reflected in the number of fraudulent activities in both the private and the public sector), stakeholders have the right to ask: where was the audit committee? Therefore, the objective of this article is to contribute to the body of knowledge by comparing the adherence of audit committee to best practices guidelines as stipulated in the King Report across public listed companies, national and provincial government departments, state-owned enterprises and local municipalities. After constructs were formed, based on the literature, factor analyses were conducted to reduce the number of variables in each construct. Thereafter, cluster analyses, which is an explorative analysis technique that classifies a set of objects in such a way that objects that are more similar are grouped into the same group, were conducted. The SPSS TwoStep Clustering Component was used, being capable of handling both continuous and categorical variables. In the first step, a pre-clustering procedure clusters the objects into small sub-clusters, after which it clusters these sub-clusters into the desired number of clusters. The cluster analyses were conducted for each construct and the measure, namely the audit opinion as listed in the external audit report, were included. Analysing 228 organisations' information, the results indicate that there is a clear distinction between the four spheres of business that has been included in the analyses, indicating certain strengths and certain weaknesses within each sphere. The results may provide the overseers of audit committees’ insight into where a specific sector’s strengths and weaknesses lie. Audit committee chairs will be able to improve the areas where their audit committee is lacking behind. The strengthening of audit committees should result in an improvement of the accountability of boards, leading to less fraud and corruption.

Keywords: audit committee disclosure, cluster analyses, governance best practices, strengths and weaknesses

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1385 Issues and Problems of Leadership Competencies among Head of Science Panels in Sarawak

Authors: Adawati Suhaili, Kamisah Osman, Mohd Effendi, Ewan Mohd Matore

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The global education reform has prompted Malaysia to transform the education system in Malaysia through the Malaysian Education Blueprint (MEB) 2013-2025. This transformation is aimed to achieve the top one-third rank in international assessment. The low achievement of student scientific literacy in TIMMS (Trends in International Mathematics and Science Study ) and PISA (Programme for International Student Assessment) has caused concern to the Ministry Of Education (MOE) despite various reform efforts. Therefore, an alternative action by enhancing the role of the Head of Science Panels (HoSPs) as a key change agent in catalyzing the improvement of student performance should be considered. Highlights of previous studies have shown that subject leadership is able to enhance teacher teaching quality in order to increase student learning. To lead the Science department and guide Science teachers more effectively, HoSPs need to strengthen their leadership skills. However, the issue of weaknesses in the leadership competencies of HoSPs in Malaysia has caused them to lack confidence and ability in leading the Science Department. The main objective of this study is to explore the factors that contribute to the problems faced by HoSPs at Sarawak in their leadership roles. This study used a qualitative design framework and using a semi-structured interview method for data collection. There were six informants involved in the interview consisting of lecturers, Senior Administrative Assistant Teacher and HoSPs. The findings of the study had been identified four main factors that contribute to problems in the leadership competencies of HoSPs in Sarawak, namely leadership practices, leadership structure, academic subjects and school change. The results are significant to the MOE in strengthening the leadership competencies of HoSPs in a more focus for improving the achievement of scientific literacy of students in Malaysia. This study can help improve the Hosps' leadership competencies in Malaysia.

Keywords: issues, problems, Malaysia education blueprint, leadership competencies, head of science panels

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1384 Electricity Generation from Renewables and Targets: An Application of Multivariate Statistical Techniques

Authors: Filiz Ersoz, Taner Ersoz, Tugrul Bayraktar

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Renewable energy is referred to as "clean energy" and common popular support for the use of renewable energy (RE) is to provide electricity with zero carbon dioxide emissions. This study provides useful insight into the European Union (EU) RE, especially, into electricity generation obtained from renewables, and their targets. The objective of this study is to identify groups of European countries, using multivariate statistical analysis and selected indicators. The hierarchical clustering method is used to decide the number of clusters for EU countries. The conducted statistical hierarchical cluster analysis is based on the Ward’s clustering method and squared Euclidean distances. Hierarchical cluster analysis identified eight distinct clusters of European countries. Then, non-hierarchical clustering (k-means) method was applied. Discriminant analysis was used to determine the validity of the results with data normalized by Z score transformation. To explore the relationship between the selected indicators, correlation coefficients were computed. The results of the study reveal the current situation of RE in European Union Member States.

Keywords: share of electricity generation, k-means clustering, discriminant, CO2 emission

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1383 Online Consortium of Independent Colleges and Universities (OCICU): Using Cluster Analysis to Grasp Student and Institutional Value of Consolidated Online Offerings in Higher Education

Authors: Alex Rodriguez, Adam Guerrero

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Purpose: This study is designed to examine the institutions that comprise the Online Consortium of Independent Colleges and Universities (OCICU) to understand better the types of higher education institutions that comprise their membership. The literature on this topic is extensive in analyzing the current economic environment around higher education, which is largely considered to be negative for independent, tuition-driven institutions, and is forcing colleges and universities to reexamine how the college-attending population defines value and how institutions can best utilize their existing resources (and those of other institutions) to meet that value expectation. The results from this analysis are intended to give OCICU the ability to target their current customer base better, based on their most notable differences, and other institutions to see how to best approach consolidation within higher education. Design/Methodology: This study utilized k-means cluster analysis in order to explore the possibility that different segments exist within the seventy-one colleges and universities that have comprised OCICU. It analyzed fifty different variables, whose selection was based on the previous literature, collected by the Integrated Postsecondary Education Data System (IPEDS), whose data is self-reported by individual institutions. Findings: OCICU member institutions are partitioned into two clusters: "access institutions" and "conventional institutions” based largely on the student profile they target. Value: The methodology of the study is relatively unique as there are not many studies within the field of higher education marketing that have employed cluster analysis, and this type of analysis has never been conducted on OCICU members, specifically, or that of any higher education consolidated offering. OCICU can use the findings of this study to obtain a better grasp as to the specific needs of the two market segments OCICU currently serves and develop measurable marketing programs around how those segments are defined that communicate the value sought by current and potential OCICU members or those of similar institutions. Other consolidation efforts within higher education can also employ the same methodology to determine their own market segments.

Keywords: Consolidation, Colleges, Enrollment, Higher Education, Marketing, Strategy, Universities

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1382 Classification of Traffic Complex Acoustic Space

Authors: Bin Wang, Jian Kang

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After years of development, the study of soundscape has been refined to the types of urban space and building. Traffic complex takes traffic function as the core, with obvious design features of architectural space combination and traffic streamline. The acoustic environment is strongly characterized by function, space, material, user and other factors. Traffic complex integrates various functions of business, accommodation, entertainment and so on. It has various forms, complex and varied experiences, and its acoustic environment is turned rich and interesting with distribution and coordination of various functions, division and unification of the mass, separation and organization of different space and the cross and the integration of multiple traffic flow. In this study, it made field recordings of each space of various traffic complex, and extracted and analyzed different acoustic elements, including changes in sound pressure, frequency distribution, steady sound source, sound source information and other aspects, to make cluster analysis of each independent traffic complex buildings. It divided complicated traffic complex building space into several typical sound space from acoustic environment perspective, mainly including stable sound space, high-pressure sound space, rhythm sound space and upheaval sound space. This classification can further deepen the study of subjective evaluation and control of the acoustic environment of traffic complex.

Keywords: soundscape, traffic complex, cluster analysis, classification

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1381 The Potential of Kepulauan Seribu as Marine-Based Eco-Geotourism Site: The Study of Carbonate Platform as Geotourism Object in Kepulauan Seribu, Jakarta

Authors: Barry Majeed, Eka Febriana, Seto Julianto

Abstract:

Kepulauan Seribu National Parks is a marine preservation region in Indonesia. It is located in 5°23' - 5°40' LS, 106°25' - 106°37' BT North of Jakarta City. Covered with area 107,489 ha, Kepulauan Seribu has a lot of tourism spots such as cluster islands, fringing reef and many more. Kepulauan Seribu is also nominated as Strategic Tourism Region In Indonesia (KSPN). So, these islands have a lot of potential sides more than preservation function as a national park, hence the development of sustainable geotourism. The aim of this study is for enhancing the development of eco-geotourism in Kepulauan Seribu. This study concern for three main aspect of eco-geotourism such as tourism, form and process. Study for the tourism aspect includes attractions, accommodations, tours, activities, interpretation, and planning & management in Kepulauan Seribu. Study for the form aspect focused on the carbonate platform situated between two islands. Primarily in carbonate reef such as head coral, branchy coral, platy coral that created the carbonate sequence in Kepulauan Seribu. Study for the process aspect primarily discussed the process of forming of carbonate from carbonate factory later becomes Kepulauan Seribu. Study for the regional geology of Kepulauan Seribu has been conducted and suggested that Kepulauan Seribu lithologies are mainly quarternary limestone. In this study, primary data was taken from an observation of quarternary carbonate platform between two islands from Hati Island, Macan Island, Bulat Island, Ubi Island and Kelapa Island. From this observation, the best routes for tourist have been made from Island to Island. Qualitative methods such as depth interview to the local people in purposive sampling also have been made. Finally, this study also giving education about geological site – carbonate sequence - in Kepulauan Seribu for the local wisdom so that this study can support the development of sustainable eco-geotourism in Kepulauan Seribu.

Keywords: carbonate factory, carbonate platform, geotourism, Kepulauan Seribu

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1380 Using Closed Frequent Itemsets for Hierarchical Document Clustering

Authors: Cheng-Jhe Lee, Chiun-Chieh Hsu

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Due to the rapid development of the Internet and the increased availability of digital documents, the excessive information on the Internet has led to information overflow problem. In order to solve these problems for effective information retrieval, document clustering in text mining becomes a popular research topic. Clustering is the unsupervised classification of data items into groups without the need of training data. Many conventional document clustering methods perform inefficiently for large document collections because they were originally designed for relational database. Therefore they are impractical in real-world document clustering and require special handling for high dimensionality and high volume. We propose the FIHC (Frequent Itemset-based Hierarchical Clustering) method, which is a hierarchical clustering method developed for document clustering, where the intuition of FIHC is that there exist some common words for each cluster. FIHC uses such words to cluster documents and builds hierarchical topic tree. In this paper, we combine FIHC algorithm with ontology to solve the semantic problem and mine the meaning behind the words in documents. Furthermore, we use the closed frequent itemsets instead of only use frequent itemsets, which increases efficiency and scalability. The experimental results show that our method is more accurate than those of well-known document clustering algorithms.

Keywords: FIHC, documents clustering, ontology, closed frequent itemset

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1379 Principal Component Analysis in Drug-Excipient Interactions

Authors: Farzad Khajavi

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Studies about the interaction between active pharmaceutical ingredients (API) and excipients are so important in the pre-formulation stage of development of all dosage forms. Analytical techniques such as differential scanning calorimetry (DSC), Thermal gravimetry (TG), and Furrier transform infrared spectroscopy (FTIR) are commonly used tools for investigating regarding compatibility and incompatibility of APIs with excipients. Sometimes the interpretation of data obtained from these techniques is difficult because of severe overlapping of API spectrum with excipients in their mixtures. Principal component analysis (PCA) as a powerful factor analytical method is used in these situations to resolve data matrices acquired from these analytical techniques. Binary mixtures of API and interested excipients are considered and produced. Peaks of FTIR, DSC, or TG of pure API and excipient and their mixtures at different mole ratios will construct the rows of the data matrix. By applying PCA on the data matrix, the number of principal components (PCs) is determined so that it contains the total variance of the data matrix. By plotting PCs or factors obtained from the score of the matrix in two-dimensional spaces if the pure API and its mixture with the excipient at the high amount of API and the 1:1mixture form a separate cluster and the other cluster comprise of the pure excipient and its blend with the API at the high amount of excipient. This confirms the existence of compatibility between API and the interested excipient. Otherwise, the incompatibility will overcome a mixture of API and excipient.

Keywords: API, compatibility, DSC, TG, interactions

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1378 Implementation of a Photo-Curable 3D Additive Manufacturing Technology with Grey Capability by Using Piezo Ink-jets

Authors: Ming-Jong Tsai, Y. L. Cheng, Y. L. Kuo, S. Y. Hsiao, J. W. Chen, P. H. Liu, D. H. Chen

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The 3D printing is a combination of digital technology, material science, intelligent manufacturing and control of opto-mechatronics systems. It is called the third industrial revolution from the view of the Economist Journal. A color 3D printing machine may provide the necessary support for high value-added industrial and commercial design, architectural design, personal boutique, and 3D artist’s creation. The main goal of this paper is to develop photo-curable color 3D manufacturing technology and system implementation. The key technologies include (1) Photo-curable color 3D additive manufacturing processes development and materials research (2) Piezo type ink-jet head control and Opto-mechatronics integration technique of the photo-curable color 3D laminated manufacturing system. The proposed system is integrated with single Piezo type ink-jet head with two individual channels for two primary UV light curable color resins which can provide for future colorful 3D printing solutions. The main research results are 16 grey levels and grey resolution of 75 dpi.

Keywords: 3D printing, additive manufacturing, color, photo-curable, Piezo type ink-jet, UV Resin

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1377 Transcriptional Evidence for the Involvement of MyD88 in Flagellin Recognition: Genomic Identification of Rock Bream MyD88 and Comparative Analysis

Authors: N. Umasuthan, S. D. N. K. Bathige, W. S. Thulasitha, I. Whang, J. Lee

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The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure. In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution. A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.

Keywords: MyD88, innate immunity, flagellin, genomic analysis

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1376 Unpleasant Symptom Clusters Influencing Quality of Life among Patients with Chronic Kidney Disease

Authors: Anucha Taiwong, Nirobol Kanogsunthornrat

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This predictive research aimed to investigate the symptom clusters that influence the quality of life among patients with chronic kidney disease, as indicated in the Theory of Unpleasant Symptoms. The purposive sample consisted of 150 patients with stage 3-4 chronic kidney disease who received care at an outpatient chronic kidney disease clinic of a tertiary hospital in Roi-Et province. Data were collected from January to March 2016 by using a patient general information form, unpleasant symptom form, and quality of life (SF-36) and were analyzed by using descriptive statistics, factor analysis, and multiple regression analysis. Findings revealed six core symptom clusters including symptom cluster of the mental and emotional conditions, peripheral nerves abnormality, fatigue, gastro-intestinal tract, pain and, waste congestion. Significant predictors for quality of life were the two symptom clusters of pain (Beta = -.220; p < .05) and the mental and emotional conditions (Beta=-.204; p<.05) which had predictive value of 19.10% (R2=.191, p<.05). This study indicated that the symptom cluster of pain and the mental and emotional conditions would worsen the patients’ quality of life. Nurses should be attentive in managing the two symptom clusters to facilitate the quality of life among patients with chronic kidney disease.

Keywords: chronic kidney disease, symptom clusters, predictors of quality of life, pre-dialysis

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1375 Genome-Wide Significant SNPs Proximal to Nicotinic Receptor Genes Impact Cognition in Schizophrenia

Authors: Mohammad Ahangari

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Schizophrenia is a psychiatric disorder with symptoms that include cognitive deficits and nicotine has been suggested to have an effect on cognition. In recent years, the advents of Genome-Wide Association Studies(GWAS) has evolved our understanding about the genetic causes of complex disorders such as schizophrenia and studying the role of genome-wide significant genes could potentially lead to the development of new therapeutic agents for treatment of cognitive deficits in schizophrenia. The current study identified six Single Nucleotide Polymorphisms (SNP) from schizophrenia and smoking GWAS that are located on or in close proximity to the nicotinic receptor gene cluster (CHRN) and studied their association with cognition in an Irish sample of 1297 cases and controls using linear regression analysis. Further on, the interaction between CHRN gene cluster and Dopamine receptor D2 gene (DRD2) during working memory was investigated. The effect of these polymorphisms on nicotinic and dopaminergic neurotransmission, which is disrupted in schizophrenia, have been characterized in terms of their effects on memory, attention, social cognition and IQ as measured by a neuropsychological test battery and significant effects in two polymorphisms were found across global IQ domain of the test battery.

Keywords: cognition, dopamine, GWAS, nicotine, schizophrenia, SNPs

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1374 Aboriginal Head and Neck Cancer Patients Have Different Patterns of Metastatic Involvement, and Have More Advanced Disease at Diagnosis

Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.

Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease

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1373 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

Abstract:

The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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1372 Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

Procedia PDF Downloads 135