Search results for: spectrum database
Commenced in January 2007
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Edition: International
Paper Count: 3045

Search results for: spectrum database

195 Gender Gap in Returns to Social Entrepreneurship

Authors: Saul Estrin, Ute Stephan, Suncica Vujic

Abstract:

Background and research question: Gender differences in pay are present at all organisational levels, including at the very top. One possible way for women to circumvent organizational norms and discrimination is to engage in entrepreneurship because, as CEOs of their own organizations, entrepreneurs largely determine their own pay. While commercial entrepreneurship plays an important role in job creation and economic growth, social entrepreneurship has come to prominence because of its promise of addressing societal challenges such as poverty, social exclusion, or environmental degradation through market-based rather than state-sponsored activities. This opens the research question whether social entrepreneurship might be a form of entrepreneurship in which the pay of men and women is the same, or at least more similar; that is to say there is little or no gender pay gap. If the gender gap in pay persists also at the top of social enterprises, what are the factors, which might explain these differences? Methodology: The Oaxaca-Blinder Decomposition (OBD) is the standard approach of decomposing the gender pay gap based on the linear regression model. The OBD divides the gender pay gap into the ‘explained’ part due to differences in labour market characteristics (education, work experience, tenure, etc.), and the ‘unexplained’ part due to differences in the returns to those characteristics. The latter part is often interpreted as ‘discrimination’. There are two issues with this approach. (i) In many countries there is a notable convergence in labour market characteristics across genders; hence the OBD method is no longer revealing, since the largest portion of the gap remains ‘unexplained’. (ii) Adding covariates to a base model sequentially either to test a particular coefficient’s ‘robustness’ or to account for the ‘effects’ on this coefficient of adding covariates might be problematic, due to sequence-sensitivity when added covariates are correlated. Gelbach’s decomposition (GD) addresses latter by using the omitted variables bias formula, which constructs a conditional decomposition thus accounting for sequence-sensitivity when added covariates are correlated. We use GD to decompose the differences in gaps of pay (annual and hourly salary), size of the organisation (revenues), effort (weekly hours of work), and sources of finances (fees and sales, grants and donations, microfinance and loans, and investors’ capital) between men and women leading social enterprises. Database: Our empirical work is made possible by our collection of a unique dataset using respondent driven sampling (RDS) methods to address the problem that there is as yet no information on the underlying population of social entrepreneurs. The countries that we focus on are the United Kingdom, Spain, Romania and Hungary. Findings and recommendations: We confirm the existence of a gender pay gap between men and women leading social enterprises. This gap can be explained by differences in the accumulation of human capital, psychological and social factors, as well as cross-country differences. The results of this study contribute to a more rounded perspective, highlighting that although social entrepreneurship may be a highly satisfying occupation, it also perpetuates gender pay inequalities.

Keywords: Gelbach’s decomposition, gender gap, returns to social entrepreneurship, values and preferences

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194 The Effect of Metabolites of Fusarium solani on the Activity of the PR-Proteins (Chitinase, β-1,3-Glucanase and Peroxidases) of Potato Tubers

Authors: A. K. Tursunova, O. V. Chebonenko, A. Zh. Amirkulova, A. O. Abaildayev, O. A. Sapko, Y. M. Dyo, A. Sh. Utarbaeva

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Fusarium solani and its variants cause root and stem rot of plants. Dry rot is the most common disease of potato tubers during storage. The causative agents of fusariosis in contact with plants behave as antagonists, growth stimulants or parasites. The diversity of host-parasite relationships is explained by the parasite’s ability to produce a wide spectrum of biologically active compounds including toxins, enzymes, oligosaccharides, antibiotic substances, enniatins and gibberellins. Many of these metabolites contribute to the creation of compatible relations; others behave as elicitors, inducing various protective responses in plants. An important part of the strategy for developing plant resistance against pathogens is the activation of protein synthesis to produce protective ‘pathogenesis-related’ proteins. The family of PR-proteins known to confer the most protective response is chitinases (EC 3.2.1.14, Cht) and β-1,3-glucanases (EC 3.2.1.39, Glu). PR-proteins also include a large multigene family of peroxidases (EC 1.11.1.7, Pod), and increased activity of Pod and expression of the Pod genes leads to the development of resistance to a broad class of pathogens. Despite intensive research on the role of PR-proteins, the question of their participation in the mechanisms of formation of the F.solani–S.tuberosum pathosуstem is not sufficiently studied. Our aim was to investigate the effect of different classes of F. solani metabolites on the activity of chitinase, β-1,3-glucanases and peroxidases in tubers of Solanum tuberosum. Metabolite culture filtrate (CF) and cytoplasmic components were fractionated by extraction of the mycelium with organic solvents, salting out techniques, dialysis, column chromatography and ultrafiltration. Protein, lipid, carbohydrate and polyphenolic fractions of fungal metabolites were derived. Using enzymatic hydrolysis we obtained oligo glycans from fungal cell walls with different molecular weights. The activity of the metabolites was tested using potato tuber discs (d = 16mm, h = 5mm). The activity of PR-proteins of tubers was analyzed in a time course of 2–24 hours. The involvement of the analysed metabolites in the modulation of both early non-specific and late related to pathogenesis reactions was demonstrated. The most effective inducer was isolated from the CF (fraction of total phenolic compounds including naphtazarins). Induction of PR-activity by this fraction was: chitinase - 340-360%, glucanase - 435-450%, soluble forms of peroxidase - 400-560%, related forms of peroxidase - 215-237%. High-inducing activity was observed by the chloroform and acetonitrile extracts of the mycelium (induction of chitinase and glucanase activity was 176-240%, of soluble and bound forms of peroxidase - 190-400%). The fraction of oligo glycans mycelium cell walls of 1.2 kDa induced chitinase and β-1,3-glucanase to 239-320%; soluble forms and related peroxidase to 198-426%. Oligo glycans cell walls of 5-10 kDa had a weak suppressor effect - chitinase (21-25%) and glucanase (25-28%) activity; had no effect on soluble forms of peroxidase, but induced to 250-270% activity related forms. The CF polysaccharides of 8.5 kDa and 3.1 kDa inhibited synchronously the glucanase and chitinase specific response in step (after 24 hours at 42-50%) and the step response induced nonspecific peroxidase activity: soluble forms 4.8 -5.2 times, associated forms 1.4-1.6 times.

Keywords: fusarium solani, PR-proteins, peroxidase, solanum tuberosum

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193 Comparison of GIS-Based Soil Erosion Susceptibility Models Using Support Vector Machine, Binary Logistic Regression and Artificial Neural Network in the Southwest Amazon Region

Authors: Elaine Lima Da Fonseca, Eliomar Pereira Da Silva Filho

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The modeling of areas susceptible to soil loss by hydro erosive processes consists of a simplified instrument of reality with the purpose of predicting future behaviors from the observation and interaction of a set of geoenvironmental factors. The models of potential areas for soil loss will be obtained through binary logistic regression, artificial neural networks, and support vector machines. The choice of the municipality of Colorado do Oeste in the south of the western Amazon is due to soil degradation due to anthropogenic activities, such as agriculture, road construction, overgrazing, deforestation, and environmental and socioeconomic configurations. Initially, a soil erosion inventory map constructed through various field investigations will be designed, including the use of remotely piloted aircraft, orbital imagery, and the PLANAFLORO/RO database. 100 sampling units with the presence of erosion will be selected based on the assumptions indicated in the literature, and, to complement the dichotomous analysis, 100 units with no erosion will be randomly designated. The next step will be the selection of the predictive parameters that exert, jointly, directly, or indirectly, some influence on the mechanism of occurrence of soil erosion events. The chosen predictors are altitude, declivity, aspect or orientation of the slope, curvature of the slope, composite topographic index, flow power index, lineament density, normalized difference vegetation index, drainage density, lithology, soil type, erosivity, and ground surface temperature. After evaluating the relative contribution of each predictor variable, the erosion susceptibility model will be applied to the municipality of Colorado do Oeste - Rondônia through the SPSS Statistic 26 software. Evaluation of the model will occur through the determination of the values of the R² of Cox & Snell and the R² of Nagelkerke, Hosmer and Lemeshow Test, Log Likelihood Value, and Wald Test, in addition to analysis of the Confounding Matrix, ROC Curve and Accumulated Gain according to the model specification. The validation of the synthesis map resulting from both models of the potential risk of soil erosion will occur by means of Kappa indices, accuracy, and sensitivity, as well as by field verification of the classes of susceptibility to erosion using drone photogrammetry. Thus, it is expected to obtain the mapping of the following classes of susceptibility to erosion very low, low, moderate, very high, and high, which may constitute a screening tool to identify areas where more detailed investigations need to be carried out, applying more efficient social resources.

Keywords: modeling, susceptibility to erosion, artificial intelligence, Amazon

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192 A Geographical Information System Supported Method for Determining Urban Transformation Areas in the Scope of Disaster Risks in Kocaeli

Authors: Tayfun Salihoğlu

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Following the Law No: 6306 on Transformation of Disaster Risk Areas, urban transformation in Turkey found its legal basis. In the best practices all over the World, the urban transformation was shaped as part of comprehensive social programs through the discourses of renewing the economic, social and physical degraded parts of the city, producing spaces resistant to earthquakes and other possible disasters and creating a livable environment. In Turkish practice, a contradictory process is observed. In this study, it is aimed to develop a method for better understanding of the urban space in terms of disaster risks in order to constitute a basis for decisions in Kocaeli Urban Transformation Master Plan, which is being prepared by Kocaeli Metropolitan Municipality. The spatial unit used in the study is the 50x50 meter grids. In order to reflect the multidimensionality of urban transformation, three basic components that have spatial data in Kocaeli were identified. These components were named as 'Problems in Built-up Areas', 'Disaster Risks arising from Geological Conditions of the Ground and Problems of Buildings', and 'Inadequacy of Urban Services'. Each component was weighted and scored for each grid. In order to delimitate urban transformation zones Optimized Outlier Analysis (Local Moran I) in the ArcGIS 10.6.1 was conducted to test the type of distribution (clustered or scattered) and its significance on the grids by assuming the weighted total score of the grid as Input Features. As a result of this analysis, it was found that the weighted total scores were not significantly clustering at all grids in urban space. The grids which the input feature is clustered significantly were exported as the new database to use in further mappings. Total Score Map reflects the significant clusters in terms of weighted total scores of 'Problems in Built-up Areas', 'Disaster Risks arising from Geological Conditions of the Ground and Problems of Buildings' and 'Inadequacy of Urban Services'. Resulting grids with the highest scores are the most likely candidates for urban transformation in this citywide study. To categorize urban space in terms of urban transformation, Grouping Analysis in ArcGIS 10.6.1 was conducted to data that includes each component scores in significantly clustered grids. Due to Pseudo Statistics and Box Plots, 6 groups with the highest F stats were extracted. As a result of the mapping of the groups, it can be said that 6 groups can be interpreted in a more meaningful manner in relation to the urban space. The method presented in this study can be magnified due to the availability of more spatial data. By integrating with other data to be obtained during the planning process, this method can contribute to the continuation of research and decision-making processes of urban transformation master plans on a more consistent basis.

Keywords: urban transformation, GIS, disaster risk assessment, Kocaeli

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191 A Sustainability Benchmarking Framework Based on the Life Cycle Sustainability Assessment: The Case of the Italian Ceramic District

Authors: A. M. Ferrari, L. Volpi, M. Pini, C. Siligardi, F. E. Garcia Muina, D. Settembre Blundo

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A long tradition in the ceramic manufacturing since the 18th century, primarily due to the availability of raw materials and an efficient transport system, let to the birth and development of the Italian ceramic tiles district that nowadays represents a reference point for this sector even at global level. This economic growth has been coupled to attention towards environmental sustainability issues throughout various initiatives undertaken over the years at the level of the production sector, such as certification activities and sustainability policies. In this way, starting from an evaluation of the sustainability in all its aspects, the present work aims to develop a benchmarking helping both producers and consumers. In the present study, throughout the Life Cycle Sustainability Assessment (LCSA) framework, the sustainability has been assessed in all its dimensions: environmental with the Life Cycle Assessment (LCA), economic with the Life Cycle Costing (LCC) and social with the Social Life Cycle Assessment (S-LCA). The annual district production of stoneware tiles during the 2016 reference year has been taken as reference flow for all the three assessments, and the system boundaries cover the entire life cycle of the tiles, except for the LCC for which only the production costs have been considered at the moment. In addition, a preliminary method for the evaluation of local and indoor emissions has been introduced in order to assess the impact due to atmospheric emissions on both people living in the area surrounding the factories and workers. The Life Cycle Assessment results, obtained from IMPACT 2002+ modified assessment method, highlight that the manufacturing process is responsible for the main impact, especially because of atmospheric emissions at a local scale, followed by the distribution to end users, the installation and the ordinary maintenance of the tiles. With regard to the economic evaluation, both the internal and external costs have been considered. For the LCC, primary data from the analysis of the financial statements of Italian ceramic companies show that the higher cost items refer to expenses for goods and services and costs of human resources. The analysis of externalities with the EPS 2015dx method attributes the main damages to the distribution and installation of the tiles. The social dimension has been investigated with a preliminary approach by using the Social Hotspots Database, and the results indicate that the most affected damage categories are health and safety and labor rights and decent work. This study shows the potential of the LCSA framework applied to an industrial sector; in particular, it can be a useful tool for building a comprehensive benchmark for the sustainability of the ceramic industry, and it can help companies to actively integrate sustainability principles into their business models.

Keywords: benchmarking, Italian ceramic industry, life cycle sustainability assessment, porcelain stoneware tiles

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190 Readout Development of a LGAD-based Hybrid Detector for Microdosimetry (HDM)

Authors: Pierobon Enrico, Missiaggia Marta, Castelluzzo Michele, Tommasino Francesco, Ricci Leonardo, Scifoni Emanuele, Vincezo Monaco, Boscardin Maurizio, La Tessa Chiara

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Clinical outcomes collected over the past three decades have suggested that ion therapy has the potential to be a treatment modality superior to conventional radiation for several types of cancer, including recurrences, as well as for other diseases. Although the results have been encouraging, numerous treatment uncertainties remain a major obstacle to the full exploitation of particle radiotherapy. To overcome therapy uncertainties optimizing treatment outcome, the best possible radiation quality description is of paramount importance linking radiation physical dose to biological effects. Microdosimetry was developed as a tool to improve the description of radiation quality. By recording the energy deposition at the micrometric scale (the typical size of a cell nucleus), this approach takes into account the non-deterministic nature of atomic and nuclear processes and creates a direct link between the dose deposited by radiation and the biological effect induced. Microdosimeters measure the spectrum of lineal energy y, defined as the energy deposition in the detector divided by most probable track length travelled by radiation. The latter is provided by the so-called “Mean Chord Length” (MCL) approximation, and it is related to the detector geometry. To improve the characterization of the radiation field quality, we define a new quantity replacing the MCL with the actual particle track length inside the microdosimeter. In order to measure this new quantity, we propose a two-stage detector consisting of a commercial Tissue Equivalent Proportional Counter (TEPC) and 4 layers of Low Gain Avalanche Detectors (LGADs) strips. The TEPC detector records the energy deposition in a region equivalent to 2 um of tissue, while the LGADs are very suitable for particle tracking because of the thickness thinnable down to tens of micrometers and fast response to ionizing radiation. The concept of HDM has been investigated and validated with Monte Carlo simulations. Currently, a dedicated readout is under development. This two stages detector will require two different systems to join complementary information for each event: energy deposition in the TEPC and respective track length recorded by LGADs tracker. This challenge is being addressed by implementing SoC (System on Chip) technology, relying on Field Programmable Gated Arrays (FPGAs) based on the Zynq architecture. TEPC readout consists of three different signal amplification legs and is carried out thanks to 3 ADCs mounted on a FPGA board. LGADs activated strip signal is processed thanks to dedicated chips, and finally, the activated strip is stored relying again on FPGA-based solutions. In this work, we will provide a detailed description of HDM geometry and the SoC solutions that we are implementing for the readout.

Keywords: particle tracking, ion therapy, low gain avalanche diode, tissue equivalent proportional counter, microdosimetry

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189 Validating Chronic Kidney Disease-Specific Risk Factors for Cardiovascular Events Using National Data: A Retrospective Cohort Study of the Nationwide Inpatient Sample

Authors: Fidelis E. Uwumiro, Chimaobi O. Nwevo, Favour O. Osemwota, Victory O. Okpujie, Emeka S. Obi, Omamuyovbi F. Nwoagbe, Ejiroghene Tejere, Joycelyn Adjei-Mensah, Christopher N. Ekeh, Charles T. Ogbodo

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Several risk factors associated with cardiovascular events have been identified as specific to Chronic Kidney Disease (CKD). This study endeavors to validate these CKD-specific risk factors using up-to-date national-level data, thereby highlighting the crucial significance of confirming the validity and generalizability of findings obtained from previous studies conducted on smaller patient populations. The study utilized the nationwide inpatient sample database to identify adult hospitalizations for CKD from 2016 to 2020, employing validated ICD-10-CM/PCS codes. A comprehensive literature review was conducted to identify both traditional and CKD-specific risk factors associated with cardiovascular events. Risk factors and cardiovascular events were defined using a combination of ICD-10-CM/PCS codes and statistical commands. Only risk factors with specific ICD-10 codes and hospitalizations with complete data were included in the study. Cardiovascular events of interest included cardiac arrhythmias, sudden cardiac death, acute heart failure, and acute coronary syndromes. Univariate and multivariate regression models were employed to evaluate the association between chronic kidney disease-specific risk factors and cardiovascular events while adjusting for the impact of traditional CV risk factors such as old age, hypertension, diabetes, hypercholesterolemia, inactivity, and smoking. A total of 690,375 hospitalizations for CKD were included in the analysis. The study population was predominantly male (375,564, 54.4%) and primarily received care at urban teaching hospitals (512,258, 74.2%). The mean age of the study population was 61 years (SD 0.1), and 86.7% (598,555) had a CCI of 3 or more. At least one traditional risk factor for CV events was present in 84.1% of all hospitalizations (580,605), while 65.4% (451,505) included at least one CKD-specific risk factor for CV events. The incidence of CV events in the study was as follows: acute coronary syndromes (41,422; 6%), sudden cardiac death (13,807; 2%), heart failure (404,560; 58.6%), and cardiac arrhythmias (124,267; 18%). 91.7% (113,912) of all cardiac arrhythmias were atrial fibrillations. Significant odds of cardiovascular events on multivariate analyses included: malnutrition (aOR: 1.09; 95% CI: 1.06–1.13; p<0.001), post-dialytic hypotension (aOR: 1.34; 95% CI: 1.26–1.42; p<0.001), thrombophilia (aOR: 1.46; 95% CI: 1.29–1.65; p<0.001), sleep disorder (aOR: 1.17; 95% CI: 1.09–1.25; p<0.001), and post-renal transplant immunosuppressive therapy (aOR: 1.39; 95% CI: 1.26–1.53; p<0.001). The study validated malnutrition, post-dialytic hypotension, thrombophilia, sleep disorders, and post-renal transplant immunosuppressive therapy, highlighting their association with increased risk for cardiovascular events in CKD patients. No significant association was observed between uremic syndrome, hyperhomocysteinemia, hyperuricemia, hypertriglyceridemia, leptin levels, carnitine deficiency, anemia, and the odds of experiencing cardiovascular events.

Keywords: cardiovascular events, cardiovascular risk factors in CKD, chronic kidney disease, nationwide inpatient sample

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188 Dys-Regulation of Immune and Inflammatory Response in in vitro Fertilization Implantation Failure Patients under Ovarian Stimulation

Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

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187 Electrical Transport through a Large-Area Self-Assembled Monolayer of Molecules Coupled with Graphene for Scalable Electronic Applications

Authors: Chunyang Miao, Bingxin Li, Shanglong Ning, Christopher J. B. Ford

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While it is challenging to fabricate electronic devices close to atomic dimensions in conventional top-down lithography, molecular electronics is promising to help maintain the exponential increase in component densities via using molecular building blocks to fabricate electronic components from the bottom up. It offers smaller, faster, and more energy-efficient electronic and photonic systems. A self-assembled monolayer (SAM) of molecules is a layer of molecules that self-assembles on a substrate. They are mechanically flexible, optically transparent, low-cost, and easy to fabricate. A large-area multi-layer structure has been designed and investigated by the team, where a SAM of designed molecules is sandwiched between graphene and gold electrodes. Each molecule can act as a quantum dot, with all molecules conducting in parallel. When a source-drain bias is applied, significant current flows only if a molecular orbital (HOMO or LUMO) lies within the source-drain energy window. If electrons tunnel sequentially on and off the molecule, the charge on the molecule is well-defined and the finite charging energy causes Coulomb blockade of transport until the molecular orbital comes within the energy window. This produces ‘Coulomb diamonds’ in the conductance vs source-drain and gate voltages. For different tunnel barriers at either end of the molecule, it is harder for electrons to tunnel out of the dot than in (or vice versa), resulting in the accumulation of two or more charges and a ‘Coulomb staircase’ in the current vs voltage. This nanostructure exhibits highly reproducible Coulomb-staircase patterns, together with additional oscillations, which are believed to be attributed to molecular vibrations. Molecules are more isolated than semiconductor dots, and so have a discrete phonon spectrum. When tunnelling into or out of a molecule, one or more vibronic states can be excited in the molecule, providing additional transport channels and resulting in additional peaks in the conductance. For useful molecular electronic devices, achieving the optimum orbital alignment of molecules to the Fermi energy in the leads is essential. To explore it, a drop of ionic liquid is employed on top of the graphene to establish an electric field at the graphene, which screens poorly, gating the molecules underneath. Results for various molecules with different alignments of Fermi energy to HOMO have shown highly reproducible Coulomb-diamond patterns, which agree reasonably with DFT calculations. In summary, this large-area SAM molecular junction is a promising candidate for future electronic circuits. (1) The small size (1-10nm) of the molecules and good flexibility of the SAM lead to the scalable assembly of ultra-high densities of functional molecules, with advantages in cost, efficiency, and power dissipation. (2) The contacting technique using graphene enables mass fabrication. (3) Its well-observed Coulomb blockade behaviour, narrow molecular resonances, and well-resolved vibronic states offer good tuneability for various functionalities, such as switches, thermoelectric generators, and memristors, etc.

Keywords: molecular electronics, Coulomb blokade, electron-phonon coupling, self-assembled monolayer

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186 Ventilator Associated Pneumonia in a Medical Intensive Care Unit, Incidence and Risk Factors: A Case Control Study

Authors: Ammar Asma, Bouafia Nabiha, Ben Cheikh Asma, Ezzi Olfa, Mahjoub Mohamed, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Ventilator-associated pneumonia (VAP) is currently recognized as one of the most relevant causes of morbidity and mortality among intensive care unit (ICU) patients worldwide. Identifying modifiable risk factors for VAP could be helpful for future controlled interventional studies aiming at improving prevention of VAP. The purposes of this study were to determine the incidence and risk factors for VAP in in a Tunisian medical ICU. Materials / Methods: A retrospective case-control study design based on the prospective database collected over a 14-month period from September 15th, 2015 through November 15th, 2016 in an 8-bed medical ICU. Patients under ventilation for over 48 h were included. The number of cases was estimated by Epi-info Software with the power of statistical test equal to 90 %. Each case patient was successfully matched to two controls according to the length of mechanical ventilation (MV) before VAP for cases and the total length of MV in controls. VAP in the ICU was defined according to American Thoracic Society; Infectious Diseases Society of America guidelines. Early onset or late-onset VAP were defined whether the infectious process occurred within or after 96 h of ICU admission. Patients’ risk factors, causes of admission, comorbidities and respiratory specimens collected were reviewed. Univariate and multivariate analyses were performed to determine variables associated with VAP with a p-value < 0.05. Results: During the period study, a total of 169 patients under mechanical ventilation were considered, 34 patients (20.11%) developed at least one episode of VAP in the ICU. The incidence rate for VAP was 14.88/1000 ventilation days. Among these cases, 9 (26.5 %) were early-onset VAP and 25 (73.5 %) were late-onset VAP. It was a certain diagnosis in 66.7% of cases. Tracheal aspiration was positive in 80% of cases. Multi-drug resistant Acinerobacter baumanii was the most common species detected in cases; 67.64% (n=23). The rate of mortality out of cases was 88.23% (n= 30). In univariate analysis, the patients with VAP were statistically more likely to suffer from cardiovascular diseases (p=0.035) and prolonged duration of sedation (p=0.009) and tracheostomy (p=0.001), they also had a higher number of re-intubation (p=0.017) and a longer total time of intubation (p=0.012). Multivariate analysis showed that cardiovascular diseases (OR= 4.44; 95% IC= [1.3 - 14]; p=0.016), tracheostomy (OR= 4.2; 95% IC= [1.16 -15.12]; p= 0.028) and prolonged duration of sedation (OR=1.21; 95% IC= [1.07, 1.36]; p=0.002) were independent risk factors for the development of VAP. Conclusion: VAP constitutes a therapeutic challenge in an ICU setting, therefore; strategies that effectively prevent VAP are needed. An infection control-training program intended to all professional heath care in this unit insisting on bundles and elaboration of procedures are planned to reduce effectively incidence rate of VAP.

Keywords: case control study, intensive care unit, risk factors, ventilator associated pneumonia

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185 Analysis of Mutation Associated with Male Infertility in Patients and Healthy Males in the Russian Population

Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

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Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

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184 Integration of Rapid Generation Technology in Pulse Crop Breeding

Authors: Saeid H. Mobini, Monika Lulsdorf, Thomas D. Warkentin

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The length of the breeding cycle from seed to seed is a limiting factor in the development of improved homozygous lines for breeding or recombinant inbred lines (RILs) for genetic analysis. The objective of this research was to accelerate the production of field pea RILs through application of rapid generation technology (RGT). RGT is based on the principle of growing miniature plants in an artificial medium under controlled conditions, and allowing them to produce a few flowers which develop seeds that are harvested prior to normal seed maturity. We aimed to maintain population size and genetic diversity in regeneration cycles. The effects of flurprimidol (a gibberellin synthesis inhibitor), plant density, hydroponic system, scheduled fertilizer applications, artificial light spectrum, photoperiod, and light/dark temperature were evaluated in the development of RILs from a cross between cultivars CDC Dakota and CDC Amarillo. The main goal was to accelerate flowering while reducing maintenance and space costs. In addition, embryo rescue of immature seeds was tested for shortening the seed fill period. Data collected over seven generations included plant height, the percentage of plant survival, flowering rate, seed setting rate, the number of seeds per plant, and time from seed to seed. Applying 0.6 µM flurprimidol reduced the internode length. Plant height was decreased to approximately 32 cm allowing for higher plant density without a delay in flowering and seed setting rate. The three light systems (T5 fluorescent bulbs, LEDs, and High Pressure Sodium +Metal-halide lamp) evaluated did not differ significantly in terms of flowering time in field pea. Collectively, the combination of 0.6 µM flurprimidol, 217 plant. m-2, 20 h photoperiod, 21/16 oC light/dark temperature in a hydroponic system with vermiculite substrate, applying scheduled fertilizer application based on growth stage, and 500 µmole.m-2.s-1 light intensity using T5 bulbs resulted in 100% of plants flowering within 34 ± 3 days and 96.5% of plants completed seed setting in 68.2 ± 3.6 days, i.e., 30-45 days/generation faster than conventional single seed descent (SSD) methods. These regeneration cycles were reproducible consistently. Hence, RGT could double (5.3) generations per year, using 3% occupying space, compared to SSD (2-3 generation/year). Embryo rescue of immature seeds at 7-8 mm stage, using commercial fertilizer solutions (Holland’s Secret™) showed seed setting rate of 95%, while younger embryos had lower germination rate. Mature embryos had a seed setting rate of 96.5% without either hormones or sugar added. So, considering the higher cost of embryo rescue using a procedure which requires skill, additional materials, and expenses, it could be removed from RGT with a further cost saving, and the process could be stopped between generations if required.

Keywords: field pea, flowering, rapid regeneration, recombinant inbred lines, single seed descent

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183 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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182 Use of a Business Intelligence Software for Interactive Visualization of Data on the Swiss Elite Sports System

Authors: Corinne Zurmuehle, Andreas Christoph Weber

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In 2019, the Swiss Federal Institute of Sport Magglingen (SFISM) conducted a mixed-methods study on the Swiss elite sports system, which yielded a large quantity of research data. In a quantitative online survey, 1151 elite sports athletes, 542 coaches, and 102 Performance Directors of national sports federations (NF) have submitted their perceptions of the national support measures of the Swiss elite sports system. These data provide an essential database for the further development of the Swiss elite sports system. The results were published in a report presenting the results divided into 40 Olympic summer and 14 winter sports (Olympic classification). The authors of this paper assume that, in practice, this division is too unspecific to assess where further measures would be needed. The aim of this paper is to find appropriate parameters for data visualization in order to identify disparities in sports promotion that allow an assessment of where further interventions by Swiss Olympic (NF umbrella organization) are required. Method: First, the variable 'salary earned from sport' was defined as a variable to measure the impact of elite sports promotion. This variable was chosen as a measure as it represents an important indicator for the professionalization of elite athletes and therefore reflects national level sports promotion measures applied by Swiss Olympic. Afterwards, the variable salary was tested with regard to the correlation between Olympic classification [a], calculating the Eta coefficient. To estimate the appropriate parameters for data visualization, the correlation between salary and four further parameters was analyzed by calculating the Eta coefficient: [a] sport; [b] prioritization (from 1 to 5) of the sports by Swiss Olympic; [c] gender; [d] employment level in sports. Results & Discussion: The analyses reveal a very small correlation between salary and Olympic classification (ɳ² = .011, p = .005). Gender demonstrates an even small correlation (ɳ² = .006, p = .014). The parameter prioritization was correlating with small effect (ɳ² = .017, p = .001) as did employment level (ɳ² = .028, p < .001). The highest correlation was identified by the parameter sport with a moderate effect (ɳ² = .075, p = .047). The analyses show that the disparities in sports promotion cannot be determined by a particular parameter but presumably explained by a combination of several parameters. We argue that the possibility of combining parameters for data visualization should be enabled when the analysis is provided to Swiss Olympic for further strategic decision-making. However, the inclusion of multiple parameters massively multiplies the number of graphs and is therefore not suitable for practical use. Therefore, we suggest to apply interactive dashboards for data visualization using Business Intelligence Software. Practical & Theoretical Contribution: This contribution provides the first attempt to use Business Intelligence Software for strategic decision-making in national level sports regarding the prioritization of national resources for sports and athletes. This allows to set specific parameters with a significant effect as filters. By using filters, parameters can be combined and compared against each other and set individually for each strategic decision.

Keywords: data visualization, business intelligence, Swiss elite sports system, strategic decision-making

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181 Neurodiversity in Post Graduate Medical Education: A Rapid Solution to Faculty Development

Authors: Sana Fatima, Paul Sadler, Jon Cooper, David Mendel, Ayesha Jameel

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Background: Neurodiversity refers to intrinsic differences between human minds and encompasses dyspraxia, dyslexia, attention deficit hyperactivity disorder, dyscalculia, autism spectrum disorder, and Tourette syndrome. There is increasing recognition of neurodiversity in relation to disability/diversity in medical education and the associated impact on training, career progression, and personal and professional wellbeing. In addition, documented and anecdotal evidence suggests that medical educators and training providers in all four nations (UK) are increasingly concerned about understanding neurodiversity and identifying and providing support for neurodivergent trainees. Summary of Work: A national Neurodiversity Task and Finish group were established to survey Health Education England local office Professional Support teams about insights into infrastructure, training for educators, triggers for assessment, resources, and intervention protocols. This group drew from educational leadership, professional and personal neurodiverse expertise, occupational medicine, employer human resource, and trainees. An online, exploratory survey was conducted to gather insights from supervisors and trainers across England using the Professional Support Units' platform. Summary of Results: This survey highlighted marked heterogeneity in the identification, assessment, and approaches to support and management of neurodivergent trainees and highlighted a 'deficit' approach to neurodiversity. It also demonstrated a paucity of educational and protocol resources for educators and supervisors in supporting neurodivergent trainees. Discussions and Conclusions: In phase one, we focused on faculty development. An educational repository for all supervising trainees using a thematic approach was formalised. This was guided by our survey findings specific for neurodiversity and took a triple 'A' approach: awareness, assessment, and action. This is further supported by video material incorporating stories in training as well as mobile workshops for trainers for more immersive learning. The subtle theme from both the survey and Task and finish group suggested a move away from deficit-focused methods toward a positive holistic, interdisciplinary approach within a biopsychosocial framework. Contributions: 1. Faculty Knowledge and basic understanding of neurodiversity are key to supporting trainees with known or underlying Neurodiverse conditions. This is further complicated by challenges around non-disclosure, varied presentations, stigma, and intersectionality. 2. There is national (and international) inconsistency in the approach to how trainees are managed once a neurodiverse condition is suspected or diagnosed. 3. A carefully constituted and focussed Task and Finish group can rapidly identify national inconsistencies in neurodiversity and implement rapid educational interventions. 4. Nuanced findings from surveys and discussion can reframe the approach to neurodiversity; from a medical model to a more comprehensive, asset-based, biopsychosocial model of support, fostering a cultural shift, accepting 'diversity' in all its manifestations, visible and hidden.

Keywords: neurodiversity, professional support, human considerations, workplace wellbeing

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180 Verification of the Supercavitation Phenomena: Investigation of the Cavity Parameters and Drag Coefficients for Different Types of Cavitator

Authors: Sezer Kefeli, Sertaç Arslan

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Supercavitation is a pressure dependent process which gives opportunity to eliminate the wetted surface effects on the underwater vehicle due to the differences of viscosity and velocity effects between liquid (freestream) and gas phase. Cavitation process occurs depending on rapid pressure drop or temperature rising in liquid phase. In this paper, pressure based cavitation is investigated due to the fact that is encountered in the underwater world, generally. Basically, this vapor-filled pressure based cavities are unstable and harmful for any underwater vehicle because these cavities (bubbles or voids) lead to intense shock waves while collapsing. On the other hand, supercavitation is a desired and stabilized phenomena than general pressure based cavitation. Supercavitation phenomena offers the idea of minimizing form drag, and thus supercavitating vehicles are revived. When proper circumstances are set up, which are either increasing the operating speed of the underwater vehicle or decreasing the pressure difference between free stream and artificial pressure, the continuity of the supercavitation is obtainable. There are 2 types of supercavitation to obtain stable and continuous supercavitation, and these are called as natural and artificial supercavitation. In order to generate natural supercavitation, various mechanical structures are discovered, which are called as cavitators. In literature, a lot of cavitator types are studied either experimentally or numerically on a CFD platforms with intent to observe natural supercavitation since the 1900s. In this paper, firstly, experimental results are obtained, and trend lines are generated based on supercavitation parameters in terms of cavitation number (), form drag coefficientC_D, dimensionless cavity diameter (d_m/d_c), and length (L_c/d_c). After that, natural cavitation verification studies are carried out for disk and cone shape cavitators. In addition, supercavitation parameters are numerically analyzed at different operating conditions, and CFD results are fitted into trend lines of experimental results. The aims of this paper are to generate one generally accepted drag coefficient equation for disk and cone cavitators at different cavitator half angle and investigation of the supercavitation parameters with respect to cavitation number. Moreover, 165 CFD analysis are performed at different cavitation numbers on FLUENT version 21R2. Five different cavitator types are modeled on SCDM with respect tocavitator’s half angles. After that, CFD database is generated depending on numerical results, and new trend lines are generated based on supercavitation parameters. These trend lines are compared with experimental results. Finally, the generally accepted drag coefficient equation and equations of supercavitation parameters are generated.

Keywords: cavity envelope, CFD, high speed underwater vehicles, supercavitation, supercavitating flows, supercavitation parameters, drag reduction, viscous force elimination, natural cavitation verification

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179 Genetically Engineered Crops: Solution for Biotic and Abiotic Stresses in Crop Production

Authors: Deepak Loura

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Production and productivity of several crops in the country continue to be adversely affected by biotic (e.g., Insect-pests and diseases) and abiotic (e.g., water temperature and salinity) stresses. Over-dependence on pesticides and other chemicals is economically non-viable for the resource-poor farmers of our country. Further, pesticides can potentially affect human and environmental safety. While traditional breeding techniques and proper- management strategies continue to play a vital role in crop improvement, we need to judiciously use biotechnology approaches for the development of genetically modified crops addressing critical problems in the improvement of crop plants for sustainable agriculture. Modern biotechnology can help to increase crop production, reduce farming costs, and improve food quality and the safety of the environment. Genetic engineering is a new technology which allows plant breeders to produce plants with new gene combinations by genetic transformation of crop plants for improvement of agronomic traits. Advances in recombinant DNA technology have made it possible to have genes between widely divergent species to develop genetically modified or genetically engineered plants. Plant genetic engineering provides the strength to harness useful genes and alleles from indigenous microorganisms to enrich the gene pool for developing genetically modified (GM) crops that will have inbuilt (inherent) resistance to insect pests, diseases, and abiotic stresses. Plant biotechnology has made significant contributions in the past 20 years in the development of genetically engineered or genetically modified crops with multiple benefits. A variety of traits have been introduced in genetically engineered crops which include (i) herbicide resistance. (ii) pest resistance, (iii) viral resistance, (iv) slow ripening of fruits and vegetables, (v) fungal and bacterial resistance, (vi) abiotic stress tolerance (drought, salinity, temperature, flooding, etc.). (vii) quality improvement (starch, protein, and oil), (viii) value addition (vitamins, micro, and macro elements), (ix) pharmaceutical and therapeutic proteins, and (x) edible vaccines, etc. Multiple genes in transgenic crops can be useful in developing durable disease resistance and a broad insect-control spectrum and could lead to potential cost-saving advantages for farmers. The development of transgenic to produce high-value pharmaceuticals and the edible vaccine is also under progress, which requires much more research and development work before commercially viable products will be available. In addition, molecular-aided selection (MAS) is now routinely used to enhance the speed and precision of plant breeding. Newer technologies need to be developed and deployed for enhancing and sustaining agricultural productivity. There is a need to optimize the use of biotechnology in conjunction with conventional technologies to achieve higher productivity with fewer resources. Therefore, genetic modification/ engineering of crop plants assumes greater importance, which demands the development and adoption of newer technology for the genetic improvement of crops for increasing crop productivity.

Keywords: biotechnology, plant genetic engineering, genetically modified, biotic, abiotic, disease resistance

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178 Improvement of Autism Diagnostic Observation Schedule Scores after Comprehensive Intensive Early Interventions in a Clinical Setting

Authors: Nils Haglund, Svenolof Dahlgren, Maria Rastam, Peik Gustafsson, Karin Kalien

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In Sweden, like in most developed countries, there is a substantial increase of children diagnosed with autism and other conditions within the autism spectrum (ASD). The rapid increase of ASD rates stresses the importance of developing care programs to provide support and comprehensive interventions for affected families. The current observational study was conducted in order to evaluate an ongoing Comprehensive Intensive Early Intervention (CIEI) program for children with autism in southern Sweden. The change in autism symptoms among children participating in CIEI (intervention group, n=67) was compared with children who received traditional habilitation services only (comparison group, n=27). Children of parents who accepted the offered CIEI-program, constituted the intervention group, whereas children, whose parents (for some reason) were not interested in the offered CIEI-program, constituted the comparison group. The CIEI-program was individualized to each child by experienced applied behavior analysis (ABA) specialists with different backgrounds as psychologists, speech pathologists or special education teachers, in cooperation with parents and preschool staff. Due to the individualization, the intervention could vary in intensity and techniques. The intensity was calculated to 15-25 hours each week at home and the preschool altogether. Each child was assigned one 'trainer', who was often employed as a preschool teacher but could have another educational background. An agreement between supervisor- parents and preschool staff was reached to confirm the intensity and content of the CIEI- program over an approximately two-year intervention period. Symptom changes were measured as evaluation-ADOS-2-scores, total- and severity-scores, minus the corresponding baseline-scores, divided by the time between baseline and evaluation. The difference between the study-groups regarding change of ADOS-2-scores was estimated using ANCOVA. In the current study, children in the CIEI-group improved their ADOS-2-total scores between baseline and evaluation (-0.8 scores per year; 95%CI: -1.2 to -0.4), whereas no such improvement was detected in the comparison group (+0.1 scores per year; 95%CI: -0.7 to +0.9). The change difference (change in the CIEI-group vs. change in the comparison group) was statistically significant, both crude and after adjusting for possible confounders (-1.1; 95%CI -1.9 to -0.4). Children in the CIEI-group also significantly improved their ADOS-calibrated severity scores, but not significantly differently so from the comparison group. The results from the current study indicate that the CIEI program significantly improves social and communicative skills among children with autism and that children with developmental delay could benefit to a similar degree as other children. The results support earlier studies reporting on the improvement of autism symptoms after early intensive interventions. The results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. Such results may be of immediate importance to healthcare organizations when allocating the already strained resources to different patient groups. Albeit the obvious limitation of the current naturalistic study, the results support previous positive studies and indicate that children with autism benefit from participating in early comprehensive, intensive programs and that investments in these programs may be highly justifiable.

Keywords: autism symptoms, ADOS-scores, evaluation, intervention program

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177 Exploring Valproic Acid (VPA) Analogues Interactions with HDAC8 Involved in VPA Mediated Teratogenicity: A Toxicoinformatics Analysis

Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

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176 Thai Cane Farmers' Responses to Sugar Policy Reforms: An Intentions Survey

Authors: Savita Tangwongkit, Chittur S Srinivasan, Philip J. Jones

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Thailand has become the world’s fourth largest sugarcane producer and second largest sugar exporter. While there have been a number of drivers of this growth, the primary driver has been wide-ranging government support measures. Recently, the Thai government has emphasized the need for policy reform as part of a broader industry restructuring to bring the sector up-to-date with the current and future developments in the international sugar market. Because of the sectors historical dependence on government support, any such reform is likely to have a very significant impact on the fortunes of Thai cane farmers. This study explores the impact of three policy scenarios, representing a spectrum of policy approaches, on Thai cane producers. These reform scenarios were designed in consultation with policy makers and academics working in the cane sector. Scenario 1 captures the current ‘government proposal’ for policy reform. This scenario removes certain domestic production subsidies but seeks to maintain as much support as is permissible under current WTO rules. The second scenario, ‘protectionism’, maintains the current internal market producer supports, but otherwise complies with international (WTO) commitments. Third, the ‘libertarian scenario’ removes all production support and market interventions, trade and domestic consumption distortions. Most important driver of producer behaviour in all of the scenarios is the producer price of cane. Cane price is obviously highest under the protectionism scenario, followed by government proposal and libertarian scenarios, respectively. Likely producer responses to these three policy scenarios was determined by means of a large-scale survey of cane farmers. The sample was stratified by size group and quotas filled by size group and region. One scenario was presented to each of three sub-samples, consisting of approx.150 farmers. Total sample size was 462 farms. Data was collected by face-to-face interview between June and August 2019. There was a marked difference in farmer response to the three scenarios. Farmers in the ‘Protectionism’ scenario, which maintains the highest cane price and those who farm larger cane areas are more likely to continue cane farming. The libertarian scenario is likely to result in the greatest losses in terms of cane production volume broadly double that of the ‘protectionism’ scenario, primarily due to farmers quitting cane production altogether. Over half of loss cane production volume comes from medium-size farm, i.e. the largest and smallest producers are the most resilient. This result is likely due to the fact that the medium size group are large enough to require hired labour but lack the economies of scale of the largest farms. Over all size groups the farms most heavily specialized in cane production, i.e. those devoting 26-50% of arable land to cane, are also the most vulnerable, with 70% of all farmers quitting cane production coming from this group. This investigation suggests that cane price is the most significant determinant of farmer behaviour. Also, that where scenarios drive significantly lower cane price, policy makers should target support towards mid-sized producers, with policies that encourage efficiency gains and diversification into alternative agricultural crops.

Keywords: farmer intentions, farm survey, policy reform, Thai cane production

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175 From Scalpel to Leadership: The Landscape for Female Neurosurgeons in the UK

Authors: Anda-veronica Gherman, Dimitrios Varthalitis

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Neurosurgery, like many surgical specialties, undoubtedly exhibits a significant gender gap, particularly in leadership positions. While increasing women representation in neurosurgery is important, it is crucial to increase their presence in leadership positions. Across the globe and Europe there are concerning trends of only 4% of all neurosurgical departments being chaired by women. This study aims to explore the situation regarding gender disparities in leadership in the United Kingdom and to identify possible contributing factors as well as discussing future strategies to bridge this gap. Methods: A literature review was conducted utilising PubMed as main database with search keywords including ‘female neurosurgeon’, ‘women neurosurgeon’, ‘gender disparity’, ‘leadership’ and ‘UK’. Additionally, a manual search of all neurosurgical departments in the UK was performed to identify the current female department leads and training director leads. Results: The literature search identified a paucity of literature addressing specifically leadership in female neurosurgeons within the UK, with very few published papers specifically on this topic. Despite more than half of medical students in the UK being female, only a small proportion pursue a surgical career, with neurosurgery being one of the least represented specialties. Only 27% of trainee neurosurgeons are female, and numbers are even lower at a consultant level, where women represent just 8%.Findings from published studies indicated that only 6.6% of leadership positions in neurosurgery are occupied by women in the UK. Furthermore, our manual searches across UK neurosurgical departments revealed that around 5% of department lead positions are currently held by women. While this figure is slightly higher than the European average of 4%, it remains lower compared to figures of 10% in other North-West European countries. The situation is slightly more positive looking at the training directors, with 15% being female. Discussion: The findings of this study highlight a significant gender disparity in leadership positions within neurosurgery in the UK, which may have important implications, perpetuating the lack of diversity on the decision-making process, limiting the career advancement opportunities of women and depriving the neurosurgical field from the voices, opinions and talents of women. With women representing half of the population, there is an undeniable need for more female leaders at the policy-making level. There are many barriers that can contribute to these numbers, including bias, stereotypes, lack of mentorship and work-like balance. A few solutions to overcome these barriers can be training programs addressing bias and impostor syndrome, leadership workshops tailored for female needs, better workplace policies, increased in formal mentorship and increasing the visibility of women in neurosurgery leadership positions through media, speaking opportunities, conferences, awards etc. And lastly, more research efforts should focus on the leadership and mentorship of women in neurosurgery, with an increased number of published papers discussing these issues.

Keywords: female neurosurgeons, female leadership, female mentorship, gender disparities

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174 Lentiviral-Based Novel Bicistronic Therapeutic Vaccine against Chronic Hepatitis B Induces Robust Immune Response

Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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173 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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172 A High-Throughput Enzyme Screening Method Using Broadband Coherent Anti-stokes Raman Spectroscopy

Authors: Ruolan Zhang, Ryo Imai, Naoko Senda, Tomoyuki Sakai

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Enzymes have attracted increasing attentions in industrial manufacturing for their applicability in catalyzing complex chemical reactions under mild conditions. Directed evolution has become a powerful approach to optimize enzymes and exploit their full potentials under the circumstance of insufficient structure-function knowledge. With the incorporation of cell-free synthetic biotechnology, rapid enzyme synthesis can be realized because no cloning procedure such as transfection is needed. Its open environment also enables direct enzyme measurement. These properties of cell-free biotechnology lead to excellent throughput of enzymes generation. However, the capabilities of current screening methods have limitations. Fluorescence-based assay needs applicable fluorescent label, and the reliability of acquired enzymatic activity is influenced by fluorescent label’s binding affinity and photostability. To acquire the natural activity of an enzyme, another method is to combine pre-screening step and high-performance liquid chromatography (HPLC) measurement. But its throughput is limited by necessary time investment. Hundreds of variants are selected from libraries, and their enzymatic activities are then identified one by one by HPLC. The turn-around-time is 30 minutes for one sample by HPLC, which limits the acquirable enzyme improvement within reasonable time. To achieve the real high-throughput enzyme screening, i.e., obtain reliable enzyme improvement within reasonable time, a widely applicable high-throughput measurement of enzymatic reactions is highly demanded. Here, a high-throughput screening method using broadband coherent anti-Stokes Raman spectroscopy (CARS) was proposed. CARS is one of coherent Raman spectroscopy, which can identify label-free chemical components specifically from their inherent molecular vibration. These characteristic vibrational signals are generated from different vibrational modes of chemical bonds. With the broadband CARS, chemicals in one sample can be identified from their signals in one broadband CARS spectrum. Moreover, it can magnify the signal levels to several orders of magnitude greater than spontaneous Raman systems, and therefore has the potential to evaluate chemical's concentration rapidly. As a demonstration of screening with CARS, alcohol dehydrogenase, which converts ethanol and nicotinamide adenine dinucleotide oxidized form (NAD+) to acetaldehyde and nicotinamide adenine dinucleotide reduced form (NADH), was used. The signal of NADH at 1660 cm⁻¹, which is generated from nicotinamide in NADH, was utilized to measure the concentration of it. The evaluation time for CARS signal of NADH was determined to be as short as 0.33 seconds while having a system sensitivity of 2.5 mM. The time course of alcohol dehydrogenase reaction was successfully measured from increasing signal intensity of NADH. This measurement result of CARS was consistent with the result of a conventional method, UV-Vis. CARS is expected to have application in high-throughput enzyme screening and realize more reliable enzyme improvement within reasonable time.

Keywords: Coherent Anti-Stokes Raman Spectroscopy, CARS, directed evolution, enzyme screening, Raman spectroscopy

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171 Sickle Cell Disease: Review of Managements in Pregnancy and the Outcome in Ampang Hospital, Selangor

Authors: Z. Nurzaireena, K. Azalea, T. Azirawaty, S. Jameela, G. Muralitharan

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The aim of this study is the review of the management practices of sickle cell disease patients during pregnancy, as well as the maternal and neonatal outcome at Ampang Hospital, Selangor. The study consisted of a review of pregnant patients with sickle cell disease under follow up at the Hematology Clinic, Ampang Hospital over the last seven years to assess their management and maternal-fetal outcome. The results of the review show that Ampang Hospital is considered the public hematology centre for sickle cell disease and had successfully managed three pregnancies throughout the last seven years. Patients’ presentations, managements and maternal-fetal outcome were compared and reviewed for academic improvements. All three patients were seen very early in their pregnancy and had been given a regime of folic acid, antibiotics and thrombo-prophylactic drugs. Close monitoring of maternal and fetal well being was done by the hematologists and obstetricians. Among the patients, there were multiple admissions during the pregnancy for either a painful sickle cell bone crisis, haemolysis following an infection and anemia requiring phenotype- matched blood and exchange transfusions. Broad spectrum antibiotics coverage during and infection, hydration, pain management and venous-thrombolism prophylaxis were mandatory. The pregnancies managed to reach near term in the third trimester but all required emergency caesarean section for obstetric indications. All pregnancies resulted in live births with good fetal outcome. During post partum all were nursed closely in the high dependency units for further complications and were discharged well. Post partum follow up and contraception counseling was comprehensively given for future pregnancies. Sickle cell disease is uncommonly seen in the East, especially in the South East Asian region, yet more cases are seen in the current decade due to improved medical expertise and advance medical laboratory technologies. Pregnancy itself is a risk factor for sickle cell patients as increased thrombosis event and risk of infections can lead to multiple crisis, haemolysis, anemia and vaso-occlusive complications including eclampsia, cerebrovasular accidents and acute bone pain. Patients mostly require multiple blood product transfusions thus phenotype-matched blood is required to reduce the risk of alloimmunozation. Emphasizing the risks and complications in preconception counseling and establishing an ultimate pregnancy plan would probably reduce the risk of morbidity and mortality to the mother and unborn child. Early management for risk of infection, thromboembolic events and adequate hydration is mandatory. A holistic approach involving multidisciplinary team care between the hematologist, obstetricians, anesthetist, neonatologist and close nursing care for both mother and baby would ensure the best outcome. In conclusion, sickle cell disease by itself is a high risk medical condition and pregnancy would further amplify the risk. Thus, close monitoring with combine multidisciplinary care, counseling and educating the patients are crucial in achieving the safe outcome.

Keywords: anaemia, haemoglobinopathies, pregnancy, sickle cell disease

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170 Bariatric Surgery Referral as an Alternative to Fundoplication in Obese Patients Presenting with GORD: A Retrospective Hospital-Based Cohort Study

Authors: T. Arkle, D. Pournaras, S. Lam, B. Kumar

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Introduction: Fundoplication is widely recognised as the best surgical option for gastro-oesophageal reflux disease (GORD) in the general population. However, there is controversy surrounding the use of conventional fundoplication in obese patients. Whilst the intra-operative failure of fundoplication, including wrap disruption, is reportedly higher in obese individuals, the more significant issue surrounds symptom recurrence post-surgery. Could a bariatric procedure be considered in obese patients for weight management, to treat the GORD, and to also reduce the risk of recurrence? Roux-en-Y gastric bypass, a widely performed bariatric procedure, has been shown to be highly successful both in controlling GORD symptoms and in weight management in obese patients. Furthermore, NICE has published clear guidelines on eligibility for bariatric surgery, with the main criteria being type 3 obesity or type 2 obesity with the presence of significant co-morbidities that would improve with weight loss. This study aims to identify the proportion of patients who undergo conventional fundoplication for GORD and/or hiatus hernia, which would have been eligible for bariatric surgery referral according to NICE guidelines. Methods: All patients who underwent fundoplication procedures for GORD and/or hiatus hernia repair at a single NHS foundation trust over a 10-year period will be identified using the Trust’s health records database. Pre-operative patient records will be used to find BMI and the presence of significant co-morbidities at the time of consideration for surgery. This information will be compared to NICE guidelines to determine potential eligibility for the bariatric surgical referral at the time of initial surgical intervention. Results: A total of 321 patients underwent fundoplication procedures between January 2011 and December 2020; 133 (41.4%) had available data for BMI or to allow BMI to be estimated. Of those 133, 40 patients (30%) had a BMI greater than 30kg/m², and 7 (5.3%) had BMI >35kg/m². One patient (0.75%) had a BMI >40 and would therefore be automatically eligible according to NICE guidelines. 4 further patients had significant co-morbidities, such as hypertension and osteoarthritis, which likely be improved by weight management surgery and therefore also indicated eligibility for referral. Overall, 3.75% (5/133) of patients undergoing conventional fundoplication procedures would have been eligible for bariatric surgical referral, these patients were all female, and the average age was 60.4 years. Conclusions: Based on this Trust’s experience, around 4% of obese patients undergoing fundoplication would have been eligible for bariatric surgical intervention. Based on current evidence, in class 2/3 obese patients, there is likely to have been a notable proportion with recurrent disease, potentially requiring further intervention. These patient’s may have benefitted more through undergoing bariatric surgery, for example a Roux-en-Y gastric bypass, addressing both their obesity and GORD. Use of patient written notes to obtain BMI data for the 188 patients with missing BMI data and further analysis to determine outcomes following fundoplication in all patients, assessing for incidence of recurrent disease, will be undertaken to strengthen conclusions.

Keywords: bariatric surgery, GORD, Nissen fundoplication, nice guidelines

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169 The Incidence of Inferior Alveolar Nerve Dysfunction Following Bilateral Sagittal Split Osteotomies: A Single Centre Retrospective Audit in the United Kingdom

Authors: Krupali Mukeshkumar, Jinesh Shah

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Background: Bilateral Sagittal Split Osteotomy (BSSO), used for the correction of mandibular deformities, is a common oral and maxillofacial surgical procedure. Inferior alveolar nerve dysfunction is commonly reported post-operatively by patients as paresthesia or anesthesia. The current literature lacks a consensus on the incidence of inferior alveolar nerve dysfunction as patients are not routinely assessed pre and post-operatively with an objective assessment. The range of incidence varies from 9% to 85% of patients, with some authors arguing that 100% of patients experience nerve dysfunction immediately post-surgery. Systematic reviews have shown a difference between incidence rates at different follow-up periods using objective and subjective methods. Aim: To identify the incidence of inferior alveolar nerve dysfunction following BSSO. Gold standard: Nerve dysfunction incidence rates similar or lower than current literature of 83% day one post-operatively and 18.4% at one year follow up. Setting: A retrospective cross-sectional audit of patients treated between 2017-2019 at the Royal Stoke University Hospital, Maxillofacial and Orthodontic departments. Sample: All patients who underwent a BSSO (with or without le fort one osteotomy) between 2017–2019 were identified from the database. Patients with pre-existing neurosensory disturbance, those who had a genioplasty at the same time and those with no follow-up were excluded. The sample consisted of 121 patients, 37 males and 84 females between the ages of 17-50 years at the time of surgery. Methods: Clinical records of 121 cases were reviewed to assess the age, sex, type of mandibular osteotomy, status of the nerve during the surgical procedure, type of bony split and incidence of nerve dysfunction at follow-up appointments. The surgical procedure was carried out by three Maxillo-facial surgeons and follow-up appointments were carried out in the Orthodontic and Oral and Maxillo-facial departments. Results: 120 patients were treated to correct the mandibular facial deformity and 1 patient was treated for sleep apnoea. Seventeen patients had a mandibular setback and 104 patients had mandibular advancement. 68 patients reported inferior alveolar nerve dysfunction at one week following their surgery. Seventy-six patients had temporary paresthesia present between 2 weeks and 12 months post-surgery. 13 patients had persistent nerve dysfunction at 12 months, of which 1 had a bad bony split during the BSSO. The incidence of nerve dysfunction postoperatively was 6.6% after 1 day, 56.1% at 1 week, 62.8% at 2 weeks, 59.5% between 3-6 weeks, 43.0% between 8-16 weeks and 10.7% at 1 year. Conclusions: The results of this audit show a similar incidence rate to the research gold standard at the one-year follow-up. Future Recommendations: No changes to surgical procedure or technique are indicated, but a need for improved documentation and a standardized approach for assessment of post-operative nerve dysfunction would be beneficial.

Keywords: bilateral sagittal split osteotomy, inferior alveolar nerve, mandible, nerve dysfunction

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168 Computer Aide Discrimination of Benign and Malignant Thyroid Nodules by Ultrasound Imaging

Authors: Akbar Gharbali, Ali Abbasian Ardekani, Afshin Mohammadi

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Introduction: Thyroid nodules have an incidence of 33-68% in the general population. More than 5-15% of these nodules are malignant. Early detection and treatment of thyroid nodules increase the cure rate and provide optimal treatment. Between the medical imaging methods, Ultrasound is the chosen imaging technique for assessment of thyroid nodules. The confirming of the diagnosis usually demands repeated fine-needle aspiration biopsy (FNAB). So, current management has morbidity and non-zero mortality. Objective: To explore diagnostic potential of automatic texture analysis (TA) methods in differentiation benign and malignant thyroid nodules by ultrasound imaging in order to help for reliable diagnosis and monitoring of the thyroid nodules in their early stages with no need biopsy. Material and Methods: The thyroid US image database consists of 70 patients (26 benign and 44 malignant) which were reported by Radiologist and proven by the biopsy. Two slices per patient were loaded in Mazda Software version 4.6 for automatic texture analysis. Regions of interests (ROIs) were defined within the abnormal part of the thyroid nodules ultrasound images. Gray levels within an ROI normalized according to three normalization schemes: N1: default or original gray levels, N2: +/- 3 Sigma or dynamic intensity limited to µ+/- 3σ, and N3: present intensity limited to 1% - 99%. Up to 270 multiscale texture features parameters per ROIs per each normalization schemes were computed from well-known statistical methods employed in Mazda software. From the statistical point of view, all calculated texture features parameters are not useful for texture analysis. So, the features based on maximum Fisher coefficient and the minimum probability of classification error and average correlation coefficients (POE+ACC) eliminated to 10 best and most effective features per normalization schemes. We analyze this feature under two standardization states (standard (S) and non-standard (NS)) with Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA) and Non-Linear Discriminant Analysis (NDA). The 1NN classifier was performed to distinguish between benign and malignant tumors. The confusion matrix and Receiver operating characteristic (ROC) curve analysis were used for the formulation of more reliable criteria of the performance of employed texture analysis methods. Results: The results demonstrated the influence of the normalization schemes and reduction methods on the effectiveness of the obtained features as a descriptor on discrimination power and classification results. The selected subset features under 1%-99% normalization, POE+ACC reduction and NDA texture analysis yielded a high discrimination performance with the area under the ROC curve (Az) of 0.9722, in distinguishing Benign from Malignant Thyroid Nodules which correspond to sensitivity of 94.45%, specificity of 100%, and accuracy of 97.14%. Conclusions: Our results indicate computer-aided diagnosis is a reliable method, and can provide useful information to help radiologists in the detection and classification of benign and malignant thyroid nodules.

Keywords: ultrasound imaging, thyroid nodules, computer aided diagnosis, texture analysis, PCA, LDA, NDA

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167 Threats to the Business Value: The Case of Mechanical Engineering Companies in the Czech Republic

Authors: Maria Reznakova, Michala Strnadova, Lukas Reznak

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Successful achievement of strategic goals requires an effective performance management system, i.e. determining the appropriate indicators measuring the rate of goal achievement. Assuming that the goal of the owners is to grow the assets they invested in, it is vital to identify the key performance indicators, which contribute to value creation. These indicators are known as value drivers. Based on the undertaken literature search, a value driver is defined as any factor that affects the value of an enterprise. The important factors are then monitored by both financial and non-financial indicators. Financial performance indicators are most useful in strategic management, since they indicate whether a company's strategy implementation and execution are contributing to bottom line improvement. Non-financial indicators are mainly used for short-term decisions. The identification of value drivers, however, is problematic for companies which are not publicly traded. Therefore financial ratios continue to be used to measure the performance of companies, despite their considerable criticism. The main drawback of such indicators is the fact that they are calculated based on accounting data, while accounting rules may differ considerably across different environments. For successful enterprise performance management it is vital to avoid factors that may reduce (or even destroy) its value. Among the known factors reducing the enterprise value are the lack of capital, lack of strategic management system and poor quality of production. In order to gain further insight into the topic, the paper presents results of the research identifying factors that adversely affect the performance of mechanical engineering enterprises in the Czech Republic. The research methodology focuses on both the qualitative and the quantitative aspect of the topic. The qualitative data were obtained from a questionnaire survey of the enterprises senior management, while the quantitative financial data were obtained from the Analysis Major Database for European Sources (AMADEUS). The questionnaire prompted managers to list factors which negatively affect business performance of their enterprises. The range of potential factors was based on a secondary research – analysis of previously undertaken questionnaire surveys and research of studies published in the scientific literature. The results of the survey were evaluated both in general, by average scores, and by detailed sub-analyses of additional criteria. These include the company specific characteristics, such as its size and ownership structure. The evaluation also included a comparison of the managers’ opinions and the performance of their enterprises – measured by return on equity and return on assets ratios. The comparisons were tested by a series of non-parametric tests of statistical significance. The results of the analyses show that the factors most detrimental to the enterprise performance include the incompetence of responsible employees and the disregard to the customers‘ requirements.

Keywords: business value, financial ratios, performance measurement, value drivers

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166 A Hardware-in-the-loop Simulation for the Development of Advanced Control System Design for a Spinal Joint Wear Simulator

Authors: Kaushikk Iyer, Richard M Hall, David Keeling

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Hardware-in-the-loop (HIL) simulation is an advanced technique for developing and testing complex real-time control systems. This paper presents the benefits of HIL simulation and how it can be implemented and used effectively to develop, test, and validate advanced control algorithms used in a spinal joint Wear simulator for the Tribological testing of spinal disc prostheses. spinal wear simulator is technologically the most advanced machine currently employed For the in-vitro testing of newly developed spinal Discimplants. However, the existing control techniques, such as a simple position control Does not allow the simulator to test non-sinusoidal waveforms. Thus, there is a need for better and advanced control methods that can be developed and tested Rigorouslybut safely before deploying it into the real simulator. A benchtop HILsetupis was created for experimentation, controller verification, and validation purposes, allowing different control strategies to be tested rapidly in a safe environment. The HIL simulation aspect in this setup attempts to replicate similar spinal motion and loading conditions. The spinal joint wear simulator containsa four-Barlinkpowered by electromechanical actuators. LabVIEW software is used to design a kinematic model of the spinal wear Simulator to Validatehow each link contributes towards the final motion of the implant under test. As a result, the implant articulates with an angular motion specified in the international standards, ISO-18192-1, that define fixed, simplified, and sinusoid motion and load profiles for wear testing of cervical disc implants. Using a PID controller, a velocity-based position control algorithm was developed to interface with the benchtop setup that performs HIL simulation. In addition to PID, a fuzzy logic controller (FLC) was also developed that acts as a supervisory controller. FLC provides intelligence to the PID controller by By automatically tuning the controller for profiles that vary in amplitude, shape, and frequency. This combination of the fuzzy-PID controller is novel to the wear testing application for spinal simulators and demonstrated superior performance against PIDwhen tested for a spectrum of frequency. Kaushikk Iyer is a Ph.D. Student at the University of Leeds and an employee at Key Engineering Solutions, Leeds, United Kingdom, (e-mail: [email protected], phone: +44 740 541 5502). Richard M Hall is with the University of Leeds, the United Kingdom as a professor in the Mechanical Engineering Department (e-mail: [email protected]). David Keeling is the managing director of Key Engineering Solutions, Leeds, United Kingdom (e-mail: [email protected]). Results obtained are successfully validated against the load and motion tolerances specified by the ISO18192-1 standard and fall within limits, that is, ±0.5° at the maxima and minima of the motion and ±2 % of the complete cycle for phasing. The simulation results prove the efficacy of the test setup using HIL simulation to verify and validate the accuracy and robustness of the prospective controller before its deployment into the spinal wear simulator. This method of testing controllers enables a wide range of possibilities to test advanced control algorithms that can potentially test even profiles of patients performing various dailyliving activities.

Keywords: Fuzzy-PID controller, hardware-in-the-loop (HIL), real-time simulation, spinal wear simulator

Procedia PDF Downloads 174