Search results for: ordinal response models

Authors: Fadi Al Khatib, Raouf Mbarki, Malek Adouni

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In various sport and recreational activities, the patellofemoral joint undergoes large forces and moments while accommodating the significant knee joint movement. In doing so, this joint is commonly the source of anterior knee pain related to instability in normal patellar tracking and excessive pressure syndrome. One well-observed explanation of the instability of the normal patellar tracking is the patellofemoral ligaments and patellar tendon damage. Improved knowledge of the damage mechanism mediating ligaments and tendon injuries can be a great help not only in rehabilitation and prevention procedures but also in the design of better reconstruction systems in the management of knee joint disorders. This damage mechanism, specifically due to excessive mechanical loading, has been linked to the micro level of the fibred structure precisely to the tropocollagen molecules and their connection density. We argue defining a clear frame starting from the bottom (micro level) to up (macro level) in the hierarchies of the soft tissue may elucidate the essential underpinning on the state of the ligaments damage. To do so, in this study a multiscale fibril reinforced hyper elastoplastic Finite Element model that accounts for the synergy between molecular and continuum syntheses was developed to determine the short-term stresses/strains patellofemoral ligaments and tendon response. The plasticity of the proposed model is associated only with the uniaxial deformation of the collagen fibril. The yield strength of the fibril is a function of the cross-link density between tropocollagen molecules, defined here by a density function. This function obtained through a Coarse-graining procedure linking nanoscale collagen features and the tissue level materials properties using molecular dynamics simulations. The hierarchies of the soft tissues were implemented using the rule of mixtures. Thereafter, the model was calibrated using a statistical calibration procedure. The model then implemented into a real structure of patellofemoral ligaments and patellar tendon (OpenKnee) and simulated under realistic loading conditions. With the calibrated material parameters the calculated axial stress lies well with the experimental measurement with a coefficient of determination (R2) equal to 0.91 and 0.92 for the patellofemoral ligaments and the patellar tendon respectively. The ‘best’ prediction of the yielding strength and strain as compared with the reported experimental data yielded when the cross-link density between the tropocollagen molecule of the fibril equal to 5.5 ± 0.5 (patellofemoral ligaments) and 12 (patellar tendon). Damage initiation of the patellofemoral ligaments was located at the femoral insertions while the damage of the patellar tendon happened in the middle of the structure. These predicted finding showed a meaningful correlation between the cross-link density of the tropocollagen molecules and the stiffness of the connective tissues of the extensor mechanism. Also, damage initiation and propagation were documented with this model, which were in satisfactory agreement with earlier observation. To the best of our knowledge, this is the first attempt to model ligaments from the bottom up, predicted depending to the tropocollagen cross-link density. This approach appears more meaningful towards a realistic simulation of a damaging process or repair attempt compared with certain published studies.

Keywords: tropocollagen, multiscale model, fibrils, knee ligaments

Procedia PDF Downloads 112

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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Authors: Sofie Verstraete, Stijn Debruyne, Frederik Desplentere

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Considering environmental issues, the interest to apply sustainable materials in industry increases. Specifically for composites, there is an emerging need for suitable materials and bonding techniques. As an alternative to traditional composites, short bio-fiber (cellulose-based flax) reinforced Polylactic Acid (PLA) is gaining popularity. However, these thermoplastic based composites show issues in adhesive bonding. This research focusses on analyzing the effects of the fibers near the bonding interphase. The research applies injection molded plate structures. A first important parameter concerns the fiber volume fraction, which directly affects adhesion characteristics of the surface. This parameter is varied between 0 (pure PLA) and 30%. Next to fiber volume fraction, the orientation of fibers near the bonding surface governs the adhesion characteristics of the injection molded parts. This parameter is not directly controlled in this work, but its effects are analyzed. Surface roughness also greatly determines surface wettability, thus adhesion. Therefore, this research work considers three different roughness conditions. Different mechanical treatments yield values up to 0.5 mm. In this preliminary research, only one adhesive type is considered. This is a two-part epoxy which is cured at 23 °C for 48 hours. In order to assure a dedicated parametric study, simple and reproduceable adhesive bonds are manufactured. Both single lap (substrate width 25 mm, thickness 3 mm, overlap length 10 mm) and double lap tests are considered since these are well documented and quite straightforward to conduct. These tests are conducted for the different substrate and surface conditions. Dog bone tensile testing is applied to retrieve the stiffness and strength characteristics of the substrates (with different fiber volume fractions). Numerical modelling (non-linear FEA) relates the effects of the considered parameters on the stiffness and strength of the different joints, obtained through the abovementioned tests. Ongoing work deals with developing dedicated numerical models, incorporating the different considered adhesion parameters. Although this work is the start of an extensive research project on the bonding characteristics of thermoplastic bio-fiber reinforced composites, some interesting results are already prominent. Firstly, a clear correlation between the surface roughness and the wettability of the substrates is observed. Given the adhesive type (and viscosity), it is noticed that an increase in surface energy is proportional to the surface roughness, to some extent. This becomes more pronounced when fiber volume fraction increases. Secondly, ultimate bond strength (single lap) also increases with increasing fiber volume fraction. On a macroscopic level, this confirms the positive effect of fibers near the adhesive bond line.

Keywords: adhesive bonding, bio-fiber reinforced composite, flax fibers, lap joint

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Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: Bill D. Geis

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Suicide wrongful death forensic cases are the fastest rising tort in mental health law. It is estimated that suicide-related cases have accounted for 15% of U.S. malpractice claims since 2006. Most suicide-related personal injury claims fall into the legal category of “wrongful death.” Though mental health experts may be called on to address a range of forensic questions in wrongful death cases, the central consultation that most experts provide is about the negligence element—specifically, the issue of whether the clinician met the clinical standard of care in assessing, treating, and managing the deceased person’s mental health care. Standards of care, varying from U.S. state to state, are broad and address what a reasonable clinician might do in a similar circumstance. This fact leaves the issue of the suicide standard of care, in each case, up to forensic experts to put forth a reasoned estimate of what the standard of care should have been in the specific case under litigation. Because the general state guidelines for standard of care are broad, forensic experts are readily retained to provide scientific and clinical opinions about whether or not a clinician met the standard of care in their suicide assessment, treatment, and management of the case. In the past and in much of current practice, the assessment of suicide has centered on the elicitation of verbalized suicide ideation. Research in recent years, however, has indicated that the majority of persons who end their lives do not say they are suicidal at their last medical or psychiatric contact. Near-term risk assessment—that goes beyond verbalized suicide ideation—is needed. Our previous research employed structural equation modeling to predict lethal suicide risk--eight negative thought patterns (feeling like a burden on others, hopelessness, self-hatred, etc.) mediated by nine transdiagnostic clinical factors (mental torment, insomnia, substance abuse, PTSD intrusions, etc.) were combined to predict acute lethal suicide risk. This structural equation model, the Lethal Suicide Risk Pattern (LSRP), Acute model, had excellent goodness-of-fit [χ2(df) = 94.25(47)***, CFI = .98, RMSEA = .05, .90CI = .03-.06, p(RMSEA = .05) = .63. AIC = 340.25, ***p < .001.]. A further SEQ analysis was completed for this paper, adding a measure of Acute Suicide Ideation to the previous SEQ. Acceptable prediction model fit was no longer achieved [χ2(df) = 3.571, CFI > .953, RMSEA = .075, .90% CI = .065-.085, AIC = 529.550].This finding suggests that, in this additional study, immediate verbalized suicide ideation information was unhelpful in the assessment of lethal risk. The LSRP and other dynamic, near-term risk models (such as the Acute Suicide Affective Disorder Model and the Suicide Crisis Syndrome Model)—going beyond elicited suicide ideation—need to be incorporated into current clinical suicide assessment training. Without this training, the standard of care for suicide assessment is out of sync with current research—an emerging dilemma for the forensic evaluation of suicide wrongful death cases.

Keywords: forensic evaluation, standard of care, suicide, suicide assessment, wrongful death

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Authors: Fabrizio Ascione, Martina Borrelli, Rosa Francesca De Masi, Silvia Ruggiero, Giuseppe Peter Vanoli

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The refurbishment of public buildings is one of the key factors of energy efficiency policy of European States. Educational buildings account for the largest share of the oldest edifice with interesting potentialities for demonstrating best practice with regards to high performance and low and zero-carbon design and for becoming exemplar cases within the community. In this context, this paper discusses the critical issue of dealing the energy refurbishment of a university building in heating dominated climate of South Italy. More in detail, the importance of using validated models will be examined exhaustively by proposing an analysis on uncertainties due to modelling assumptions mainly referring to the adoption of stochastic schedules for occupant behavior and equipment or lighting usage. Indeed, today, the great part of commercial tools provides to designers a library of possible schedules with which thermal zones can be described. Very often, the users do not pay close attention to diversify thermal zones and to modify or to adapt predefined profiles, and results of designing are affected positively or negatively without any alarm about it. Data such as occupancy schedules, internal loads and the interaction between people and windows or plant systems, represent some of the largest variables during the energy modelling and to understand calibration results. This is mainly due to the adoption of discrete standardized and conventional schedules with important consequences on the prevision of the energy consumptions. The problem is surely difficult to examine and to solve. In this paper, a sensitivity analysis is presented, to understand what is the order of magnitude of error that is committed by varying the deterministic schedules used for occupation, internal load, and lighting system. This could be a typical uncertainty for a case study as the presented one where there is not a regulation system for the HVAC system thus the occupant cannot interact with it. More in detail, starting from adopted schedules, created according to questioner’ s responses and that has allowed a good calibration of energy simulation model, several different scenarios are tested. Two type of analysis are presented: the reference building is compared with these scenarios in term of percentage difference on the projected total electric energy need and natural gas request. Then the different entries of consumption are analyzed and for more interesting cases also the comparison between calibration indexes. Moreover, for the optimal refurbishment solution, the same simulations are done. The variation on the provision of energy saving and global cost reduction is evidenced. This parametric study wants to underline the effect on performance indexes evaluation of the modelling assumptions during the description of thermal zones.

Keywords: energy simulation, modelling calibration, occupant behavior, university building

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Authors: Mai Sirhan, Arieh Sidess

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Asphaltic mixture is a heterogeneous material composed of three main components: aggregates; bitumen and air voids. The professional experience and scientific literature categorize asphaltic mixture as a viscoelastic material, whose behavior is determined by temperature and loading rate. Properties characterization of the asphaltic mixture used under the service conditions is done by compacting and testing cylindric asphalt samples in the laboratory. These samples must resemble in a high degree internal structure of the mixture achieved in service, and the mechanical characteristics of the compacted asphalt layer in the pavement. The laboratory samples are usually compacted in temperatures between 140 and 160 degrees Celsius. In this temperature range, the asphalt has a low degree of strength. The laboratory samples are compacted using the dynamic or vibrational compaction methods. In the compaction process, the aggregates tend to align themselves in certain directions that lead to anisotropic behavior of the asphaltic mixture. This issue has been studied in the Strategic Highway Research Program (SHRP) research, that recommended using the gyratory compactor based on the assumption that this method is the best in mimicking the compaction in the service. In Israel, the Netivei Israel company is considering adopting the Gyratory Method as a replacement for the Marshall method used today. Therefore, the compatibility of the Gyratory Method for the use with Israeli asphaltic mixtures should be investigated. In this research, we aimed to examine the impact of the compaction method used on the mechanical characteristics of the asphaltic mixtures and to evaluate the degree of anisotropy in relation to the compaction method. In order to carry out this research, samples have been compacted in the vibratory and gyratory compactors. These samples were cylindrically cored both vertically (compaction wise) and horizontally (perpendicular to compaction direction). These models were tested under dynamic modulus and permanent deformation tests. The comparable results of the tests proved that: (1) specimens compacted by the vibratory compactor had higher dynamic modulus values than the specimens compacted by the gyratory compactor (2) both vibratory and gyratory compacted specimens had anisotropic behavior, especially in high temperatures. Also, the degree of anisotropy is higher in specimens compacted by the gyratory method. (3) Specimens compacted by the vibratory method that were cored vertically had the highest resistance to rutting. On the other hand, specimens compacted by the vibratory method that were cored horizontally had the lowest resistance to rutting. Additionally (4) these differences between the different types of specimens rise mainly due to the different internal arrangement of aggregates resulting from the compaction method. (5) Based on the initial prediction of the performance of the flexible pavement containing an asphalt layer having characteristics based on the results achieved in this research. It can be concluded that there is a significant impact of the compaction method and the degree of anisotropy on the strains that develop in the pavement, and the resistance of the pavement to fatigue and rutting defects.

Keywords: anisotropy, asphalt compaction, dynamic modulus, gyratory compactor, mechanical properties, permanent deformation, vibratory compactor

Procedia PDF Downloads 101

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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Authors: Magdalena Suárez-Ortega, M. Fe. Sánchez-García

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This paper focuses on the analysis of the motivations that lead people to undertake and consolidate their business. It is addressed from the framework of planned behavior theory, which recognizes the importance of the social environment and cultural values, both in the decision to undertake business and in business consolidation. Similarly, it is also based on theories of career development, which emphasize the importance of career management competencies and their connections to other vital aspects of people, including their roles within their families and other personal activities. This connects directly with the impact of entrepreneurship on the career and the professional-personal project of each individual. This study is part of the project titled Career Design and Talent Management (Ministry of Economy and Competitiveness of Spain, State Plan 2013-2016 Excellence Ref. EDU2013-45704-P). The aim of the study is to identify and describe entrepreneurial competencies and motivational profiles in a sample of 248 Spanish entrepreneurs, considering the consolidated profile and the profile in transition (n = 248).In order to obtain the information, the Questionnaire of Motivation and conditioners of the entrepreneurial career (MCEC) has been applied. This consists of 67 items and includes four scales (E1-Conflicts in conciliation, E2-Satisfaction in the career path, E3-Motivations to undertake, E4-Guidance Needs). Cluster analysis (mixed method, combining k-means clustering with a hierarchical method) was carried out, characterizing the groups profiles according to the categorical variables (chi square, p = 0.05), and the quantitative variables (ANOVA). The results have allowed us to characterize three motivational profiles relevant to the motivation, the degree of conciliation between personal and professional life, and the degree of conflict in conciliation, levels of career satisfaction and orientation needs (in the entrepreneurial project and life-career). The first profile is formed by extrinsically motivated entrepreneurs, professionally satisfied and without conflict of vital roles. The second profile acts with intrinsic motivation and also associated with family models, and although it shows satisfaction with their professional career, it finds a high conflict in their family and professional life. The third is composed of entrepreneurs with high extrinsic motivation, professional dissatisfaction and at the same time, feel the conflict in their professional life by the effect of personal roles. Ultimately, the analysis has allowed us to line the kinds of entrepreneurs to different levels of motivation, satisfaction, needs and articulation in professional and personal life, showing characterizations associated with the use of time for leisure, and the care of the family. Associations related to gender, age, activity sector, environment (rural, urban, virtual), and the use of time for domestic tasks are not identified. The model obtained and its implications for the design of training actions and orientation to entrepreneurs is also discussed.

Keywords: motivation, entrepreneurial career, guidance needs, life-work balance, job satisfaction, assessment

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Authors: George R. Puno, Eric N. Bruno

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The natural landscape of the Philippine archipelago plus the current realities of climate change make the country vulnerable to flood hazards. Flooding becomes the recurring natural disaster in the country resulting to lose of lives and properties. Musimusi is among the rivers which exhibited inundation particularly at the inhabited floodplain portion of its watershed. During the event, rescue operations and distribution of relief goods become a problem due to lack of high resolution flood maps to aid local government unit identify the most affected areas. In the attempt of minimizing impact of flooding, hydrologic modelling with high resolution mapping is becoming more challenging and important. This study focused on the analysis of flood extent as a function of different geomorphologic characteristics of Musimusi watershed. The methods include the delineation of morphometric parameters in the Musimusi watershed using Geographic Information System (GIS) and geometric calculations tools. Digital Terrain Model (DTM) as one of the derivatives of Light Detection and Ranging (LiDAR) technology was used to determine the extent of river inundation involving the application of Hydrologic Engineering Center-River Analysis System (HEC-RAS) and Hydrology Modelling System (HEC-HMS) models. The digital elevation model (DEM) from synthetic Aperture Radar (SAR) was used to delineate watershed boundary and river network. Datasets like mean sea level, river cross section, river stage, discharge and rainfall were also used as input parameters. Curve number (CN), vegetation, and soil properties were calibrated based on the existing condition of the site. Results showed that the drainage density value of the watershed is low which indicates that the basin is highly permeable subsoil and thick vegetative cover. The watershed’s elongation ratio value of 0.9 implies that the floodplain portion of the watershed is susceptible to flooding. The bifurcation ratio value of 2.1 indicates higher risk of flooding in localized areas of the watershed. The circularity ratio value (1.20) indicates that the basin is circular in shape, high discharge of runoff and low permeability of the subsoil condition. The heavy rainfall of 167 mm brought by Typhoon Seniang last December 29, 2014 was characterized as high intensity and long duration, with a return period of 100 years produced 316 m3s-1 outflows. Portion of the floodplain zone (1.52%) suffered inundation with 2.76 m depth at the maximum. The information generated in this study is helpful to the local disaster risk reduction management council in monitoring the affected sites for more appropriate decisions so that cost of rescue operations and relief goods distribution is minimized.

Keywords: flooding, geomorphology, mapping, watershed

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Authors: Faith Abdul Rasak Asharaf

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Every city has a threshold known as urban carrying capacity based on which it can withstand a particular density of people, above which the city might need to resort to measures like expanding its boundaries or growing vertically. As a result of this circumstance, the number of squatter communities is growing, as is the claustrophobic feeling of being confined inside a "concrete jungle." The expansion of suburbs, commercial areas, and industrial real estate in the areas surrounding medium-sized cities has resulted in changes to their landscapes and urban forms, as well as a systematic shift in their role in the urban hierarchy when functional endowment and connections to other territories are considered. The urban carrying capacity idea provides crucial guidance for city administrators and planners in better managing, designing, planning, constructing, and distributing urban resources to satisfy the huge demands of an evergrowing urban population. An ecological footprint is a criterion of urban carrying capacity, which is the amount of land required to provide humanity with renewable resources and absorb its trash. However, as each piece of land has its unique carrying capacity, including ecological, social, and economic considerations, these metropolitan areas begin to reach a saturation point over time. Various city models have been tried throughout the years to meet the increasing urban population density by moving the zones of work, life, and leisure to achieve maximum sustainable growth. The current scenario is that of a vertical city and compact city concept, in which the maximum density of people is attempted to fit into a definite area using efficient land use and a variety of other strategies, but this has proven to be a very unsustainable method of growth, as evidenced by the COVID-19 period. Due to a shortage of housing and basic infrastructure, densely populated cities gave rise to massive squatter communities, unable to accommodate the overflowing migrants. To achieve optimum carrying capacity, planning measures such as polycentric city and diffuse city concepts can be implemented, which will help to relieve the congested city core by relocating certain sectors of the town to the city periphery, which will help to create newer spaces for design in terms of public space, transportation, and housing, which is a major concern in the current scenario. The study's goal is focused on suggesting design options and solutions in terms of placemaking for better urban quality and urban life for the citizens once city centres have been de-densified based on urban carrying capacity and ecological footprint, taking the case of Kochi as an apt example of a highly densified city core, focusing on Edappally, which is an agglomeration of many urban factors.

Keywords: urban carrying capacity, urbanization, urban sprawl, ecological footprint

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Authors: Carina Emminger, Umut D. Cakmak, Evrim Burkut, Rene Preuer, Ingrid Graz, Zoltan Major

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Damping accompanies us daily in everyday life and is used to protect (e.g., in shoes) and make our life more comfortable (damping of unwanted motion) and calm (noise reduction). In general, damping is the absorption of energy which is either stored in the material (vibration isolation systems) or changed into heat (vibration absorbers). In case of the last, the damping mechanism can be split in active, passive, as well as semi-active (a combination of active and passive). Active damping is required to enable an almost perfect damping over the whole application range and is used, for instance, in sport cars. In contrast, passive damping is a response of the material due to external loading. Consequently, the material composition has a huge influence on the damping behavior. For elastomers, the material behavior is inherent viscoelastic, temperature, and frequency dependent. However, passive damping is not adjustable during application. Therefore, it is of importance to understand the fundamental viscoelastic behavior and the dissipation capability due to external loading. The objective of this work is to assess the limitation and applicability of viscoelastic material damping for applications in which currently coil-over shock absorbers are utilized. Coil-over shock absorbers are usually made of various mechanical parts and incorporate fluids within the damper. These shock absorbers are well-known and studied in the industry, and when needed, they can be easily adjusted during their product lifetime. In contrary, dampers made of – ideally – a single material are more resource efficient, have an easier serviceability, and are easier manufactured. However, they lack of adaptability and adjustability in service. Therefore, a case study with a remote-controlled sport car was conducted. The original shock absorbers were redesigned, and the spring-dashpot system was replaced by both an elastomer and a thermoplastic-elastomer, respectively. Here, five different formulations of elastomers were used, including a pure and an iron-particle filled thermoplastic poly(urethan) (TPU) and blends of two different poly(dimethyl siloxane) (PDMS). In addition, the TPUs were investigated as full and hollow dampers to investigate the difference between solid and structured material. To get comparative results each material formulation was comprehensively characterized, by monotonic uniaxial compression tests, dynamic thermomechanical analysis (DTMA), and rebound resilience. Moreover, the new material-based shock absorbers were compared with spring-dashpot shock absorbers. The shock absorbers were analyzed under monotonic and cyclic loading. In addition, an impact loading was applied on the remote-controlled car to measure the damping properties in operation. A servo-hydraulic high-speed linear actuator was utilized to apply the loads. The acceleration of the car and the displacement of specific measurement points were recorded while testing by a sensor and high-speed camera, respectively. The results prove that elastomers are suitable in damping applications, but they are temperature and frequency dependent. This is a limitation in applicability of viscous material damper. Feasible fields of application may be in the case of micromobility, like bicycles, e-scooters, and e-skateboards. Furthermore, the viscous material damping could be used to increase the inherent damping of a whole structure, e.g., in bicycle-frames.

Keywords: damper structures, material damping, PDMS, TPU

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Paul Flynn, Luke O’Donnell

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There is a pressing societal need for educators in formal and non-formal settings to develop pedagogical frameworks, programmes, and interventions that support the development of transversal skills for life beyond the classroom. These skills include communication, collaboration, interpersonal relationship building, problem-solving, and planning, and organizational skills; or lifeworld literacies encountered first hand. This is particularly true for young people aged between 15-18. This demographic represents both the future of society and those best positioned to take advantage of well-designed, structured educational supports within and across formal and non-formal settings. Secondary school history has been identified as an appropriate area of study which deftly develops many of those transversal skills so crucial to positive societal engagement. However, in the formal context, students often challenge history’s relevance to their own lived experience and dismiss it as a study option. In response to such challenges, teachers will often design stimulating lessons which are often well-received. That said, some students continue to question modern-day connections, presenting a persistent and pervasive classroom distraction. The continuing decline in numbers opting to study second-level history indicates an erosion of what should be a critical opportunity to develop all-important lifeworld literacies within formal education. In contrast, students readily acknowledge relevance in non-formal settings where many participants meaningfully engage with history by way of student-focused activities. Furthermore, many do so without predesigned pedagogical aids which support transversal skills development as embodied learning outcomes. As this paper will present, there is a dearth of work pertaining to the circular subject of history and its embodied learning outcomes, including lifeworld literacies, in formal and non-formal settings. While frequently challenging to reconcile formal (often defined by strict curricula and examination processes), and non-formal engagement with history, opportunities do exist. In the Irish context, this is exemplified by a popular university outreach programme: breaking the SEAL. This programme supports second-level history students as they fulfill curriculum requirements in completing a research study report. This report is a student-led research project pulling on communication skills, collaboration with peers and teachers, interpersonal relationships, problem-solving, and planning and organizational skills. Completion of this process has been widely recognized as excellent preparation not only for higher education (third level) but work-life demands as well. Within a formal education setting, the RSR harnesses non-formal learning virtues and exposes students to limited aspects of independent learning that relate to a professional work setting –a lifeworld literacy. Breaking the SEAL provides opportunities for students to enhance their lifeworld literacy by engaging in an independent research and learning process within the protective security of the classroom and its teacher. This paper will highlight the critical role this programme plays in preparing participating students (n=315) for life after compulsory education and presents examples of how lifeworld literacies may be developed through a scaffolded process of historical research and reporting anchored in non-formal contexts.

Keywords: history, education, literacy, transversal skills

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Authors: Neeti Nayak, Khalid Duri

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Despite the many advances made in transportation planning, the number of injuries and fatalities in the United States which involve motorized vehicles near intersections remain largely unchanged year over year. Data from the National Highway Traffic Safety Administration for 2018 indicates accidents involving motorized vehicles at traffic intersections accounted for 8,245 deaths and 914,811 injuries. Furthermore, collisions involving pedal cyclists killed 861 people (38% at intersections) and injured 46,295 (68% at intersections), while accidents involving pedestrians claimed 6,247 lives (25% at intersections) and injured 71,887 (56% at intersections)- the highest tallies registered in nearly 20 years. Some of the causes attributed to the rising number of accidents relate to increasing populations and the associated changes in land and traffic usage patterns, insufficient visibility conditions, and inadequate applications of traffic controls. Intersections that were initially designed with a particular land use pattern in mind may be rendered obsolete by subsequent developments. Many accidents involving pedestrians are accounted for by locations which should have been designed for safe crosswalks. Conventional solutions for evaluating intersection safety often require costly deployment of engineering surveys and analysis, which limit the capacity of resource-constrained administrations to satisfy their community’s needs for safe roadways adequately, effectively relegating mitigation efforts for high-risk areas to post-incident responses. This paper demonstrates how geospatial technology can identify high-risk locations and evaluate the viability of specific intersection management techniques. GIS is used to simulate relevant real-world conditions- the presence of traffic controls, zoning records, locations of interest for human activity, design speed of roadways, topographic details and immovable structures. The proposed methodology provides a low-cost mechanism for empowering urban planners to reduce the risks of accidents using 2-dimensional data representing multi-modal street networks, parcels, crosswalks and demographic information alongside 3-dimensional models of buildings, elevation, slope and aspect surfaces to evaluate visibility and lighting conditions and estimate probabilities for jaywalking and risks posed by blind or uncontrolled intersections. The proposed tools were developed using sample areas of Southern California, but the model will scale to other cities which conform to similar transportation standards given the availability of relevant GIS data.

Keywords: crosswalks, cyclist safety, geotechnology, GIS, intersection safety, pedestrian safety, roadway safety, transportation planning, urban design

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Authors: John Lachapelle

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Introduction: Neural stimulation is increasingly targeted toward treatment of back pain, PTSD, Parkinson’s disease, and for sensory perception. Sensory recording during stimulation is important in order to examine neural response to stimulation. Most neural amplifiers (headstages) focus on noise efficiency factor (NEF). Conversely, neural headstages need to handle artifacts from several sources including power lines, movement (EMG), and neural stimulation itself. In this work a layered approach to artifact rejection is used to reduce corruption of the neural ENG signal by 60dBv, resulting in recovery of sensory signals in rats and primates that would previously not be possible. Methods: The approach combines analog techniques to reduce and handle unwanted signal amplitudes. The methods include optimized (1) sensory electrode placement, (2) amplifier configuration, and (3) artifact blanking when necessary. The techniques together are like concentric moats protecting a castle; only the wanted neural signal can penetrate. There are two conditions in which the headstage operates: unwanted artifact < 50mV, linear operation, and artifact > 50mV, fast-settle gain reduction signal limiting (covered in more detail in a separate paper). Unwanted Signals at the headstage input: Consider: (a) EMG signals are by nature < 10mV. (b) 60 Hz power line signals may be > 50mV with poor electrode cable conditions; with careful routing much of the signal is common to both reference and active electrode and rejected in the differential amplifier with <50mV remaining. (c) An unwanted (to the neural recorder) stimulation signal is attenuated from stimulation to sensory electrode. The voltage seen at the sensory electrode can be modeled Φ_m=I_o/4πσr. For a 1 mA stimulation signal, with 1 cm spacing between electrodes, the signal is <20mV at the headstage. Headstage ASIC design: The front end ASIC design is designed to produce < 1% THD at 50mV input; 50 times higher than typical headstage ASICs, with no increase in noise floor. This requires careful balance of amplifier stages in the headstage ASIC, as well as consideration of the electrodes effect on noise. The ASIC is designed to allow extremely small signal extraction on low impedance (< 10kohm) electrodes with configuration of the headstage ASIC noise floor to < 700nV/rt-Hz. Smaller high impedance electrodes (> 100kohm) are typically located closer to neural sources and transduce higher amplitude signals (> 10uV); the ASIC low-power mode conserves power with 2uV/rt-Hz noise. Findings: The enhanced neural processing ASIC has been compared with a commercial neural recording amplifier IC. Chronically implanted primates at MGH demonstrated the presence of commercial neural amplifier saturation as a result of large environmental artifacts. The enhanced artifact suppression headstage ASIC, in the same setup, was able to recover and process the wanted neural signal separately from the suppressed unwanted artifacts. Separately, the enhanced artifact suppression headstage ASIC was able to separate sensory neural signals from unwanted artifacts in mouse-implanted peripheral intrafascicular electrodes. Conclusion: Optimizing headstage ASICs allow observation of neural signals in the presence of large artifacts that will be present in real-life implanted applications, and are targeted toward human implantation in the DARPA HAPTIX program.

Keywords: ASIC, biosensors, biomedical signal processing, biomedical sensors

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

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Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

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Authors: Pulkeria Pascoe, Hawa P. Tundui, Marcia Dutra de Barcellos, Hans de Steur, Xavier Gellynck

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A majority of Micro and Small Enterprises (MSEs) experience low or no growth. Understanding their performance remains unfinished and disjointed as there is no consensus on the factors influencing it, especially in developing countries. Using a Resource-Based View (RBV) as the theoretical background, this cross-sectional study employed four regression models to examine the influence of firm-level factors (firm-specific characteristics, firm resources, manager socio-demographic characteristics, and selected management practices) on the overall performance variations among 442 Tanzanian micro and small agri-food processing firms. Study results confirmed the RBV argument that intangible resources make a larger contribution to overall performance variations among firms than that tangible resources. Firms' tangible and intangible resources explained 34.5% of overall performance variations (intangible resources explained the overall performance variability by 19.4% compared to tangible resources, which accounted for 15.1%), ranking first in explaining the overall performance variance. Firm-specific characteristics ranked second by influencing variations in overall performance by 29.0%. Selected management practices ranked third (6.3%), while the manager's socio-demographic factors were last on the list, as they influenced the overall performance variability among firms by only 5.1%. The study also found that firms that focus on proper utilization of tangible resources (financial and physical), set targets, and undertake better working capital management practices performed higher than their counterparts (low and average performers). Furthermore, accumulation and proper utilization of intangible resources (relational, organizational, and reputational), undertaking performance monitoring practices, age of the manager, and the choice of the firm location and activity were the dominant significant factors influencing the variations among average and high performers, relative to low performers. The entrepreneurial background was a significant factor influencing variations in average and low-performing firms, indicating that entrepreneurial skills are crucial to achieving average levels of performance. Firm age, size, legal status, source of start-up capital, gender, education level, and total business experience of the manager were not statistically significant variables influencing the overall performance variations among the agri-food processors under the study. The study has identified both significant and non-significant factors influencing performance variations among low, average, and high-performing micro and small agri-food processing firms in Tanzania. Therefore, results from this study will help managers, policymakers and researchers to identify areas where more attention should be placed in order to improve overall performance of MSEs in agri-food industry.

Keywords: firm-level factors, micro and small enterprises, performance, regression analysis, resource-based-view

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Authors: Elisa Santana-Monagas, Juan L. Núñez, Jaime León, Samuel Falcón, Celia Fernández, Rocío P. Solís

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Students’ emotional experiences have been a widely discussed theme among researchers, proving a central role on students’ outcomes. Yet, up to now, far too little attention has been paid to teaching practices that negatively relate with students’ negative emotions in the higher education. The present work aims to examine the relationship between teachers’ teaching practices (i.e., students’ evaluations of teaching and autonomy support), the students’ feelings of boredom and agentic engagement and motivation in the higher education context. To do so, the present study incorporates one of the most popular tools in natural processing language to address students’ evaluations of teaching: sentiment analysis. Whereas most research has focused on the creation of SA models and assessing students’ satisfaction regarding teachers and courses to the author’s best knowledge, no research before has included results from SA into an explanatory model. A total of 225 university students (Mean age = 26.16, SD = 7.4, 78.7 % women) participated in the study. Students were enrolled in degree and masters’ studies at the faculty of Education of a public university of Spain. Data was collected using an online questionnaire students could access through a QR code they completed during a teaching period where the assessed teacher was not present. To assess students’ sentiments towards their teachers’ teaching, we asked them the following open-ended question: “If you had to explain a peer who doesn't know your teacher how he or she communicates in class, what would you tell them?”. Sentiment analysis was performed with Microsoft's pre-trained model. For this study, we relied on the probability of the students answer belonging to the negative category. To assess the reliability of the measure, inter-rater agreement between this NLP tool and one of the researchers, who independently coded all answers, was examined. The average pairwise percent agreement and the Cohen’s kappa were calculated with ReCal2. The agreement reached was of 90.8% and Cohen’s kappa .68, both considered satisfactory. To test the hypothesis relations a structural equation model (SEM) was estimated. Results showed that the model fit indices displayed a good fit to the data; χ² (134) = 351.129, p < .001, RMSEA = .07, SRMR = .09, TLI = .91, CFI = .92. Specifically, results show that boredom was negatively predicted by autonomy support practices (β = -.47[-.61, -.33]), whereas for the negative sentiment extracted from SET, this relation was positive (β = .23[.16, .30]). In other words, when students’ opinion towards their instructors’ teaching practices was negative, it was more likely for them to feel bored. Regarding the relations among boredom and student outcomes, results showed a negative predictive value of boredom on students’ motivation to study (β = -.46[-.63, -.29]) and agentic engagement (β = -.24[-.33, -.15]). Altogether, results show a promising future for sentiment analysis techniques in the field of education as they proved the usefulness of this tool when evaluating relations among teaching practices and student outcomes.

Keywords: sentiment analysis, boredom, motivation, agentic engagement

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Authors: Ayodele James Akinola

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This study investigated the use of English in doctor-patient interaction in a university teaching hospital from a southwestern state in Nigeria with the aim of identifying the role of communication in an L2, patterns of communication, discourse strategies, pragmatic acts, and contexts that shape the interaction. Jacob Mey’s Pragmatic Acts notion complemented with Emanuel and Emanuel’s model of doctor-patient relationship provided the theoretical standpoint. Data comprising 7 audio-recorded doctors-patient interactions were collected from a University Hospital in Oyo state, Nigeria. Interactions involving the use of English language were purposefully selected. These were supplemented with patients’ case notes and interviews conducted with doctors. Transcription was patterned alongside modified Arminen’s notations of conversation analysis. In the study, interaction in English between doctor and patients has the preponderance of direct-translation, code-mixing and switching, Nigerianism and use of cultural worldviews to express medical experience. Irrespective of these, three patterns communication, namely the paternalistic, interpretive, and deliberative were identified. These were exhibited through varying discourse strategies. The paternalistic model reflected slightly casual conversational conventions and registers. These were achieved through the pragmemic activities of situated speech acts, psychological and physical acts, via patients’ quarrel-induced acts, controlled and managed through doctors’ shared situation knowledge. All these produced empathising, pacifying, promising and instructing practs. The patients’ practs were explaining, provoking, associating and greeting in the paternalistic model. The informative model reveals the use of adjacency pairs, formal turn-taking, precise detailing, institutional talks and dialogic strategies. Through the activities of the speech, prosody and physical acts, the practs of declaring, alerting and informing were utilised by doctors, while the patients exploited adapting, requesting and selecting practs. The negotiating conversational strategy of the deliberative model featured in the speech, prosody and physical acts. In this model, practs of suggesting, teaching, persuading and convincing were utilised by the doctors. The patients deployed the practs of questioning, demanding, considering and deciding. The contextual variables revealed that other patterns (such as phatic and informative) are also used and they coalesced in the hospital within the situational and psychological contexts. However, the paternalistic model was predominantly employed by doctors with over six years in practice, while the interpretive, informative and deliberative models were found among registrar and others below six years of medical practice. Doctors’ experience, patients’ peculiarities and shared cultural knowledge influenced doctor-patient communication in the study.

Keywords: pragmatics, communication pattern, doctor-patient interaction, Nigerian hospital situation

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Authors: Calorine Twebaze, Jesca Balinga

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Field X is located on the Eastern shores of L. Albert, Uganda, on the rift flank where the gross sedimentary fill is typically less than 2,000m. The field was discovered in 2006 and encountered about 20.4m of net pay across three (3) stratigraphic intervals within the discovery well. The field covers an area of 3 km2, with the structural configuration comprising a 3-way dip-closed hanging wall anticline that seals against the basement to the southeast along the bounding fault. Field X had been mapped on reprocessed 3D seismic data, which was originally acquired in 2007 and reprocessed in 2013. The seismic data quality is good across the field, and reprocessing work reduced the uncertainty in the location of the bounding fault and enhanced the lateral continuity of reservoir reflectors. The current study was a re-evaluation of Field X to refine fault interpretation and understand the structural uncertainties associated with the field. The seismic data, and three (3) wells datasets were used during the study. The evaluation followed standard workflows using Petrel software and structural attribute analysis. The process spanned from seismic- -well tie, structural interpretation, and structural uncertainty analysis. Analysis of three (3) well ties generated for the 3 wells provided a geophysical interpretation that was consistent with geological picks. The generated time-depth curves showed a general increase in velocity with burial depth. However, separation in curve trends observed below 1100m was mainly attributed to minimal lateral variation in velocity between the wells. In addition to Attribute analysis, three velocity modeling approaches were evaluated, including the Time-Depth Curve, Vo+ kZ, and Average Velocity Method. The generated models were calibrated at well locations using well tops to obtain the best velocity model for Field X. The Time-depth method resulted in more reliable depth surfaces with good structural coherence between the TWT and depth maps with minimal error at well locations of 2 to 5m. Both the NNE-SSW rift border fault and minor faults in the existing interpretation were reevaluated. However, the new interpretation delineated an E-W trending fault in the northern part of the field that had not been interpreted before. The fault was interpreted at all stratigraphic levels and thus propagates from the basement to the surface and is an active fault today. It was also noted that the entire field is less faulted with more faults in the deeper part of the field. The major structural uncertainties defined included 1) The time horizons due to reduced data quality, especially in the deeper parts of the structure, an error equal to one-third of the reflection time thickness was assumed, 2) Check shot analysis showed varying velocities within the wells thus varying depth values for each well, and 3) Very few average velocity points due to limited wells produced a pessimistic average Velocity model.

Keywords: 3D seismic data interpretation, structural uncertainties, attribute analysis, velocity modelling approaches

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Authors: Vadim Allheily, Rudiger Schmitt, Lionel Merlat, Gildas L'Hostis

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Inflight devices are nowadays major actors in both military and civilian landscapes. Among others, missiles, mortars, rockets or even drones this last decade are increasingly sophisticated, and it is today of prior manner to develop always more efficient defensive systems from all these potential threats. In this frame, recent High Energy Laser weapon prototypes (HEL) have demonstrated some extremely good operational abilities to shot down within seconds flying targets several kilometers off. Whereas test outcomes are promising from both experimental and cost-related perspectives, the deterioration process still needs to be explored to be able to closely predict the effects of a high-energy laser irradiation on typical structures, heading finally to an effective design of laser sources and protective countermeasures. Laser matter interaction researches have a long history of more than 40 years at the French-German Research Institute (ISL). Those studies were tied with laser sources development in the mid-60s, mainly for specific metrology of fast phenomena. Nowadays, laser matter interaction can be viewed as the terminal ballistics of conventional weapons, with the unique capability of laser beams to carry energy at light velocity over large ranges. In the last years, a strong focus was made at ISL on the interaction process of laser radiation with metal targets such as artillery shells. Due to the absorbed laser radiation and the resulting heating process, an encased explosive charge can be initiated resulting in deflagration or even detonation of the projectile in flight. Drones and Unmanned Air Vehicles (UAVs) are of outmost interests in modern warfare. Those aerial systems are usually made up of polymer-based composite materials, whose complexity involves new scientific challenges. Aside this main laser-matter interaction activity, a lot of experimental and numerical knowledge has been gathered at ISL within domains like spectrometry, thermodynamics or mechanics. Techniques and devices were developed to study separately each aspect concerned by this topic; optical characterization, thermal investigations, chemical reactions analysis or mechanical examinations are beyond carried out to neatly estimate essential key values. Results from these diverse tasks are then incorporated into analytic or FE numerical models that were elaborated, for example, to predict thermal repercussion on explosive charges or mechanical failures of structures. These simulations highlight the influence of each phenomenon during the laser irradiation and forecast experimental observations with good accuracy.

Keywords: composite materials, countermeasure, experimental work, high-energy laser, laser-matter interaction, modeling

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Authors: Luciano Tarantino

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Gas gangrene is a rare, severe infection with a very high mortality rate caused by Clostridium species. The infection causes a non-suppurative localized producing gas lesion from which harmful toxins that impair the inflammatory response cause vessel damage and multiple organ failure. Gas gangrene of the liver is very rare and develops suddenly, often as a complication of abdominal surgery and liver transplantation. The present paper deals with a case of gas gangrene of the liver that occurred after percutaneous MW ablation of hepatocellular carcinoma, resulting in progressive liver necrosis and multi-organ failure in spite of specific antibiotics administration. The patient was successfully treated with percutaneous Radiofrequency ablation. Case report: Female, 76 years old, Child A class cirrhosis, treated with synchronous insertion of 3 MW antennae for large HCC (5.5 cm) in the VIII segment. 24 hours after treatment, the patient was asymptomatic and left the hospital . 2 days later, she complained of fever, weakness, abdominal swelling, and pain. Abdominal US detected a 2.3 cm in size gas-containing area, eccentric within the large (7 cm) ablated area. The patient was promptly hospitalized with the diagnosis of anaerobic liver abscess and started antibiotic therapy with Imipenem/cilastatine+metronidazole+teicoplanine. On the fourth day, the patient was moved to the ICU because of dyspnea, congestive heart failure, atrial fibrillation, right pleural effusion, ascites, and renal failure. Blood tests demonstrated severe leukopenia and neutropenia, anemia, increased creatinine and blood nitrogen, high-level FDP, and high INR. Blood cultures were negative. At US, unenhanced CT, and CEUS, a progressive enlargement of the infected liver lesion was observed. Percutaneous drainage was attempted, but only drops of non-suppurative brownish material could be obtained. Pleural and peritoneal drainages gave serosanguineous muddy fluid. The Surgeon and the Anesthesiologist excluded any indication of surgical resection because of the high perioperative mortality risk. Therefore, we asked for the informed consent of the patient and her relatives to treat the gangrenous liver lesion by percutaneous Ablation. Under conscious sedation, percutaneous RFA of GG was performed by double insertion of 3 cool-tip needles (Covidien LDT, USA ) into the infected area. The procedure was well tolerated by the patient. A dramatic improvement in the patient's condition was observed in the subsequent 24 hours and thereafter. Fever and dyspnea disappeared. Normalization of blood tests, including creatinine, was observed within 4 days. Heart performance improved, 10 days after the RFA the patient left the hospital and was followed-up with weekly as an outpatient for 2 months and every two months thereafter. At 18 months follow-up, the patient is well compensated (Child-Pugh class B7), without any peritoneal or pleural effusion and without any HCC recurrence at imaging (US every 3 months, CT every 6 months). Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients non-responder to antibiotics and when surgery and liver transplantation are not feasible. A fast and early indication is needed in case of rapid worsening of patient's conditions.

Keywords: liver tumor ablation, interventional ultrasound, liver infection, gas gangrene, radiofrequency ablation

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin

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The Argentine stem weevil (ASW; L. bonariensis) is an economically important pasture pest in New Zealand, which causes about $200 million of damage per annum. Microctonus hyperodae (Mh), a parasite of the ASW in its natural range in South America, was introduced into New Zealand to curb the pasture damage caused by the ASW. Mh is an endoparasitic wasp that lays its eggs in the ASW halting its reproduction. Mh was initially successful at preventing ASW proliferation and reducing pasture damage. The effectiveness of Mh has since declined due to decreased parasitism rates and has resulted in increased pasture damage. Although the mechanism through which ASW has developed resistance to Mh has not been discovered, it has been proposed to be due to the different reproductive modes used by Mh and the ASW in New Zealand. The ASW reproduces sexually, whereas Mh reproduces asexually, which has been hypothesised to have allowed the ASW to ‘out evolve’ Mh. Other species within the Microctonus genus reproduce both sexually and asexually. Strains of Microctonus aethiopoides (Ma), a species closely related to Mh, reproduce either by sexual or asexual reproduction. Comparing the genomes of sexual and asexual Microctonus may allow for the identification of the mechanism of asexual reproduction and other characteristics that may improve Mh as a biocontrol agent. The genomes of Mh and three strains of Ma, two of which reproduce sexually and one reproduces asexually, have been sequenced and annotated. The French (MaFR) and Moroccan (MaMO) reproduce sexually, whereas the Irish strain (MaIR) reproduces asexually. Like Mh, The Ma strains are also used as biocontrol agents, but for different weevil species. The genomes of Mh and MaIR were subsequently upgraded using Hi-C, resulting in a set of high quality, highly contiguous genomes. A subset of the genes involved in mitosis and meiosis, which have been identified though the use of Hidden Markov Models generated from genes involved in these processes in other Hymenoptera, have been catalogued in Mh and the strains of Ma. Meiosis and mitosis genes were broadly conserved in both sexual and asexual Microctonus species. This implies that either the asexual species have retained a subset of the molecular components required for sexual reproduction or that the molecular mechanisms of mitosis and meiosis are different or differently regulated in Microctonus to other insect species in which these mechanisms are more broadly characterised. Bioinformatic analysis of the chemoreceptor compliment in Microctonus has revealed some variation in the number of olfactory receptors, which may be related to host preference. Phylogenetic analysis of olfactory receptors highlights variation, which may be able to explain different host range preferences in the Microctonus. Hi-C clustering implies that Mh has 12 chromosomes, and MaIR has 8. Hence there may be variation in gene regulation between species. Genome alignment of Mh and MaIR implies that there may be large scale genome structural variation. Greater insight into the genetics of these agriculturally important group of parasitic wasps may be beneficial in restoring or maintaining their biocontrol efficacy.

Keywords: argentine stem weevil, asexual, genomics, Microctonus hyperodae

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Authors: Jayden R. Hunter, Brett A. Gordon, Stephen R. Bird, Amanda C. Benson

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The World Health Organisation recognises the workplace as an important setting for exercise promotion, with potential benefits including improved employee health and fitness, and reduced worker absenteeism and presenteeism. Despite these potential benefits to both employee and employer, there is a lack of evidence supporting the long-term effectiveness of workplace exercise programs. There is, therefore, a need for better-informed programs that cater to employee exercise preferences. Specifically, workplace exercise programs should address any time, motivation, internal and external barriers to participation reported by sub-groups of employees. This study sought to compare exercise participation to perceived barriers and facilitators to workplace exercise engagement of university employees. This information is needed to design and implement wider-reaching programs aiming to maximise long-term employee exercise adherence and subsequent health, fitness and productivity benefits. An online survey was advertised at an Australian university with the potential to reach 3,104 full-time employees. Along with exercise participation (International physical activity questionnaire) and behaviour (stage of behaviour change in relation to physical activity questionnaire), perceived barriers (corporate exercise barriers scale) and facilitators to workplace exercise participation were identified. The survey response rate was 8.1% (252 full-time employees; 95% white-collar; 60% female; 79.4% aged 30–59 years; 57% professional and 38% academic). Most employees reported meeting (43.7%) or exceeding (42.9%) exercise guidelines over the previous week (i.e. ⩾30 min of moderate-intensity exercise on most days or ⩾ 25 min of vigorous-intensity exercise on at least three days per week). Reported exercise behaviour over the previous six months showed that 64.7% of employees were in maintenance, 8.3% were in action, 10.9% were in preparation, 12.4% were in contemplation, and 3.8% were in the pre-contemplation stage of change. Perceived barriers towards workplace exercise participation were significantly higher in employees not attaining weekly exercise guidelines compared to employees meeting or exceeding guidelines, including a lack of time or reduced motivation (p < 0.001; partial eta squared = 0.24 (large effect)), exercise attitude (p < 0.05; partial eta squared = 0.04 (small effect)), internal (p < 0.01; partial eta squared = 0.10 (moderate effect)) and external (p < 0.01; partial eta squared = 0.06 (moderate effect)) barriers. The most frequently reported exercise facilitators were personal training (particularly for insufficiently active employees; 33%) and group exercise classes (20%). The most frequently cited preferred modes of exercise were walking (70%), swimming (50%), gym (48%), and cycling (45%). In conclusion, providing additional means of support such as individualised gym, swimming and cycling programs with personal supervision and guidance may be particularly useful for employees not meeting recommended moderate-vigorous volumes of exercise, to help overcome reported exercise barriers in order to improve participation, health, and fitness. While individual biopsychosocial factors should be considered when making recommendations for interventions, the specific barriers and facilitators to workplace exercise participation identified by this study can inform the development of workplace exercise programs aiming to broaden employee engagement and promote greater ongoing exercise adherence. This is especially important for the uptake of less active employees who perceive greater barriers to workplace exercise participation than their more active colleagues.

Keywords: exercise barriers, exercise facilitators, physical activity, workplace health

Procedia PDF Downloads 128

Authors: Antonella Falanga, Armando Cartenì

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Today, an unprecedented amount of data coming from several sources, including mobile devices, sensors, tracking systems, and online platforms, characterizes our lives. The term “big data” not only refers to the quantity of data but also to the variety and speed of data generation. These data hold valuable insights that, when extracted and analyzed, facilitate informed decision-making. The 4Vs of big data - velocity, volume, variety, and value - highlight essential aspects, showcasing the rapid generation, vast quantities, diverse sources, and potential value addition of these kinds of data. This surge of information has revolutionized many sectors, such as business for improving decision-making processes, healthcare for clinical record analysis and medical research, education for enhancing teaching methodologies, agriculture for optimizing crop management, finance for risk assessment and fraud detection, media and entertainment for personalized content recommendations, emergency for a real-time response during crisis/events, and also mobility for the urban planning and for the design/management of public and private transport services. Big data's pervasive impact enhances societal aspects, elevating the quality of life, service efficiency, and problem-solving capacities. However, during this transformative era, new challenges arise, including data quality, privacy, data security, cybersecurity, interoperability, the need for advanced infrastructures, and staff training. Within the transportation sector (the one investigated in this research), applications span planning, designing, and managing systems and mobility services. Among the most common big data applications within the transport sector are, for example, real-time traffic monitoring, bus/freight vehicle route optimization, vehicle maintenance, road safety and all the autonomous and connected vehicles applications. Benefits include a reduction in travel times, road accidents and pollutant emissions. Within these issues, the proper transport demand estimation is crucial for sustainable transportation planning. Evaluating the impact of sustainable mobility policies starts with a quantitative analysis of travel demand. Achieving transportation decarbonization goals hinges on precise estimations of demand for individual transport modes. Emerging technologies, offering substantial big data at lower costs than traditional methods, play a pivotal role in this context. Starting from these considerations, this study explores the usefulness impact of big data within transport demand estimation. This research focuses on leveraging (big) data collected during the COVID-19 pandemic to estimate the evolution of the mobility demand in Italy. Estimation results reveal in the post-COVID-19 era, more than 96 million national daily trips, about 2.6 trips per capita, with a mobile population of more than 37.6 million Italian travelers per day. Overall, this research allows us to conclude that big data better enhances rational decision-making for mobility demand estimation, which is imperative for adeptly planning and allocating investments in transportation infrastructures and services.

Keywords: big data, cloud computing, decision-making, mobility demand, transportation

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

Procedia PDF Downloads 111