Search results for: clinically relevant

Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Muthukuda Arachchige Dona Shiroma Jeeva Shirajanie Niriella

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Suppressing terrorism and ensuring peace and security of the people is one of the topics which have gained serious attention of the world community. Commissions of terrorist activities, locally and internationally lead to an uncertainty of peace and security, violations of human rights of the people. Thereby it demands stringent security laws and strong criminal justice systems, both at domestic and international levels. This paper intends to evaluate security laws in Sri Lanka through the criminal justice perspective, including their efficacy in relation to combat terrorism. The paper further intends to discuss the importance of such laws in upholding the peace and security at both local and universal levels. The paper argues that the term ‘efficacy’ does not stand for, sending people to jail at large-scale, but the ability to combat terrorism crime without violating the rights of the innocent people. The qualitative research method is followed to conduct this research which contains an extensive examination of security laws available as counter-terrorism laws in Sri Lanka with the relevant international standards adopted by the UN treaties. Primary sources which are relevant to the research, including judicial pronouncements are also discussed in this regard. Secondary sources such as reports, research articles and textbooks on this topic and information available on the internet are also reviewed in this analysis.

Keywords: terrorism, security laws, criminal justice system, Sri Lanka, international treaty law

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Authors: Tonny Ograh, Joshua Ayarkwa, Dickson Osei-Asibey, Alex Acheampong, Peter Amoah

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Theories are used to improve the conceptualization of research ideas. These theories enhance valuable elucidations that help us to grasp the meaning of research findings. Nevertheless, the use of theories to promote studies in green supplier selection in procurement decisions has attracted little attention. With the emergence of sustainable procurement, public procurement practitioners in Ghana are yet to achieve relevant knowledge on green supplier selections due to insufficient knowledge and inadequate appropriate frameworks. The flagrancy of the consequences of public procurers’ failure to integrate environmental considerations into supplier selection explains the adoption of a multi-theory approach for comprehension of the dynamics of green integration into supplier selection. In this paper, the practicality of three theories for improving the understanding of the influential factors enhancing the integration of environmental sustainability into supplier selection was reviewed. The three theories are Resource-Based Theory, Human Capital Theory and Absorptive Capacity Theory. This review uncovered knowledge management, top management commitment, and environmental management capabilities as important elements needed for the integration of environmental sustainability into supplier selection in public procurement. The theoretical review yielded a framework that conceptualizes knowledge and capabilities of practitioners relevant to the incorporation of environmental sustainability into supplier selection in public procurement.

Keywords: environmental, sustainability, supplier selection, environmental procurement, sustainable procurement

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Authors: O. A. Adeyemi, M. O. Idris, W. A. Oke, O. T. Olorode, S. O. Alayande, A. E. Adeoye

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The purpose of this paper is to investigate the process of capability building at subsidiary level and the challenges to such process. The relevance of external factors for capability development, have not been explicitly addressed in empirical studies. Though, internal factors, acting as enablers, have been more extensively studied. With reference to external factors, subsidiaries are actively influenced by specific characteristics of the host country, implying a need to become fully immersed in local culture and practices. Specifically, in MNCs, there has been a widespread trend in management practice to increase subsidiary autonomy,  with subsidiary managers being encouraged to act entrepreneurially, and to take advantage of host country specificity. As such, it could be proposed that: P1: The degree at which subsidiary management is connected to the host country, will positively influence the capability development process. Dynamic capabilities reside to a large measure with the subsidiary management team, but are impacted by the organizational processes, systems and structures that the MNC headquarter has designed to manage its business. At the subsidiary level, the weight of the subsidiary in the network, its initiative-taking and its profile building increase the supportive attention of the HQs and are relevant to the success of the process of capability building. Therefore, our second proposition is that: P2: Subsidiary role and HQ support are relevant elements in capability development at the subsidiary level. Design/Methodology/Approach: This present study will adopt the multiple case studies approach. That is because a case study research is relevant when addressing issues without known empirical evidences or with little developed prior theory. The key definitions and literature sources directly connected with operations of western subsidiaries in emerging markets, such as China, are well established. A qualitative approach, i.e., case studies of three western subsidiaries, will be adopted. The companies have similar products, they have operations in China, and both of them are mature in their internationalization process. Interviews with key informants, annual reports, press releases, media materials, presentation material to customers and stakeholders, and other company documents will be used as data sources. Findings: Western Subsidiaries in Emerging Market operate in a way substantially different from those in the West. What are the conditions initiating the outsourcing of operations? The paper will discuss and present two relevant propositions guiding that process. Practical Implications: MNCs headquarter should be aware of the potential for capability development at the subsidiary level. This increased awareness could induce consideration in headquarter about the possible ways of encouraging such known capability development and how to leverage these capabilities for better MNC headquarter and/or subsidiary performance. Originality/Value: The paper is expected to contribute on the theme: drivers of subsidiary performance with focus on emerging market. In particular, it will show how some external conditions could promote a capability-building process within subsidiaries.

Keywords: case studies, dynamic capability, emerging market, subsidiary

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Authors: Ditsapelo M. McFarland

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Background: Despite the availability of the Pap smear services in urban areas in Botswana, most women in such areas do not seem to screen regular for prevention of the cervical cancer disease. Reasons for non-use of the available Pap smear services are not well understood. Beliefs about cancer may influence participation in cancer screening in these women. The purpose of this study was to develop an instrument to measure beliefs about cervical cancer and Pap smear screening among Black women in Botswana, and evaluate the psychometric properties of the instrument. Significance: Instruments that are designed to measure beliefs about cervical cancer and screening among black women in Botswana, as well as in the surrounding region, are presently not available. Valid and reliable instruments are needed for exploration of the women’s beliefs about cervical cancer. Conceptual Framework: The Health Belief Model (HBM) provided a conceptual framework for the study. Methodology: The study was done in four phases: Phase 1: item generation: 15 items were generated from literature review and qualitative data for each of four conceptually defined HBM constructs: Perceived susceptibility, severity, benefits, and barriers (Version 1). Phase 2: content validity: Four experts who were advanced practice nurses of African descent and were familiar with the content and the HBM evaluated the content. Experts rated the items on a 4-point Likert scale ranging from: 1=not relevant, 2=somewhat relevant, 3=relevant and 4=very relevant. Fifty-five items were retained for instrument development: perceived susceptibility - 11, severity - 14, benefits - 15 and barriers - 15, all measuring on a 4-point Likert scale ranging from strongly disagree (1) to strongly agree (4). (Version 2). Phase 3: pilot testing: The instrument was pilot tested on a convenient sample of 30 women in Botswana and revised as needed. Phase 4: reliability: the revised instrument (Version 3) was submitted to a larger sample of women in Botswana (n=300) for reliability testing. The sample included women who were Batswana by birth and decent, were aged 30 years and above and could complete an English questionnaire. Data were collected with the assistance of trained research assistants. Major findings: confirmatory factor analysis of the 55 items found that a number of items did not adequately load in a four-factor solution. Items that exhibited reasonable reliability and had low frequency of missing values (n=36) were retained: perceived barriers (14 items), perceived benefits (8 items), perceived severity (4 items), and perceived susceptibility (10 items). confirmatory factor analysis (principle components) for a four factor solution using varimax rotation demonstrated that these four factors explained 43% of the variation in these 36 items. Conclusion: reliability analysis using Cronbach’s Alpha gave generally satisfactory results with values from 0.53 to 0.89.

Keywords: cervical cancer, factor analysis, psychometric evaluation, varimax rotation

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Authors: Isabelle Lorge, Napoleon Katsos

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BACKGROUND: Children growing up in a multilingual environment face challenges related to the need to monitor the speaker’s linguistic abilities, more frequent communication failures, and having to acquire a large number of words in a limited amount of time compared to monolinguals. As a result, bilingual learners may develop different word learning strategies, rely more on some strategies than others, and engage cognitive resources such as theory of mind and attention skills in different ways. HYPOTHESIS: The goal of our study is to investigate whether multilingual exposure leads to improvements in the ability to use pragmatic inference for word learning, i.e., to use speaker cues to derive their referring intentions, often by overcoming lower level salience effects. The speaker cues we identified as relevant are (a) use of a modifier with or without stress (‘the WET dax’ prompting the choice of the referent which has a dry counterpart), (b) referent extension (‘this is a kitten with a fep’ prompting the choice of the unique rather than shared object), (c) referent novelty (choosing novel action rather than novel object which has been manipulated already), (d) teacher versus random sampling (assuming the choice of specific examples for a novel word to be relevant to the extension of that new category), and finally (e) emotional affect (‘look at the figoo’ uttered in a sad or happy voice) . METHOD: To this end, we implemented on a touchscreen computer a task corresponding to each of the cues above, where the child had to pick the referent of a novel word. These word learning tasks (a), (b), (c), (d) and (e) were adapted from previous word learning studies. 113 children have been tested (54 reception and 59 year 1, ranging from 4 to 6 years old) in a London primary school. Bilingual or monolingual status and other relevant information (age of onset, proficiency, literacy for bilinguals) is ascertained through language questionnaires from parents (34 out of 113 received to date). While we do not yet have the data that will allow us to test for effect of bilingualism, we can already see that performances are far from approaching ceiling in any of the tasks. In some cases the children’s performances radically differ from adults’ in a qualitative way, which means that there is scope for quantitative and qualitative effects to arise between language groups. The findings should contribute to explain the puzzling speed and efficiency that bilinguals demonstrate in acquiring competence in two languages.

Keywords: bilingualism, pragmatics, word learning, attention

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Authors: Kazunari Ozaki, Mitsuru Kageyama, Kenki Miyazawa, Yoshio Nakamura

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Background: Kampo (Japanese Traditional medicine) is a medicine traditionally practiced in Japan, based on ancient Chinese medicine. Most Kampo doctors have used decoction of crude drug pieces for treatment. 93% of the Kampo drugs sold in Japan are Kampo products nowadays. Of all Kampo products, 81% of them are Kampo extract formulations for prescription, which is prepared in powdered or granulated form from medicinal crude drug extracts mixed with appropriate excipient. Physicians with medical license for Western medicine prescribe these Kampo extract formulations for prescription in Japan. Objectives: Our study aims at presenting a brief history of Kampo extract formulations for prescription in Japan. Methods: Systematic searches for relevant studies were conducted using not only printed journals but also electronic journals from the bibliographic databases, such as PubMed/Medline, Ichushi-Web, and university/institutional websites, as well as search engines, such as Google and Google Scholar. Results: The first commercialization of Kampo extract formulations for general use (or OTC (over-the-counter) Kampo extract formulation) was achieved after 1957. The number of drugs has been subsequentially increased, reaching 148 Kampo extract formulation for prescription currently. Conclusion: We provide a history of Kampo extract formulations for prescription in Japan. The originality of this research is that it analyzes the background history of Kampo in parallel with relevant transitions in the government and insurance systems.

Keywords: health insurance system, history, Kampo, Kampo extract formulation for prescription, OTC Kampo extract formulation, pattern corresponding prescription (Ho-sho-so-tai) system

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Authors: Benjamin Beltzung, Marie Pelé, Julien P. Renoult, Cédric Sueur

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To this day, it is not known if drawing is specifically human behavior or if this behavior finds its origins in ancestor species. An interesting window to enlighten this question is to analyze the drawing behavior in genetically close to human species, such as non-human primate species. A good candidate for this approach is the orangutan, who shares 97% of our genes and exhibits multiple human-like behaviors. Focusing on figurative aspects may not be suitable for orangutans’ drawings, which may appear as scribbles but may have meaning. A manual feature selection would lead to an anthropocentric bias, as the features selected by humans may not match with those relevant for orangutans. In the present study, we used deep learning to analyze the drawings of a female orangutan named Molly († in 2011), who has produced 1,299 drawings in her last five years as part of a behavioral enrichment program at the Tama Zoo in Japan. We investigate multiple ways to decipher Molly’s drawings. First, we demonstrate the existence of differences between seasons by training a deep learning model to classify Molly’s drawings according to the seasons. Then, to understand and interpret these seasonal differences, we analyze how the information spreads within the network, from shallow to deep layers, where early layers encode simple local features and deep layers encode more complex and global information. More precisely, we investigate the impact of feature complexity on classification accuracy through features extraction fed to a Support Vector Machine. Last, we leverage style transfer to dissociate features associated with drawing style from those describing the representational content and analyze the relative importance of these two types of features in explaining seasonal variation. Content features were relevant for the classification, showing the presence of meaning in these non-figurative drawings and the ability of deep learning to decipher these differences. The style of the drawings was also relevant, as style features encoded enough information to have a classification better than random. The accuracy of style features was higher for deeper layers, demonstrating and highlighting the variation of style between seasons in Molly’s drawings. Through this study, we demonstrate how deep learning can help at finding meanings in non-figurative drawings and interpret these differences.

Keywords: cognition, deep learning, drawing behavior, interpretability

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Authors: A. M. U. P. Kumari, Vidanapathirana. J., Amarasekara J., Karunanayaka L.

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Leptospirosis is a zoonotic infection with significant morbidity and mortality. As an occupational disease, it has become a global concern due to its disease burden in endemic countries and rural areas. The aim of this study was to assess disease burden in terms of DALYs of leptospirosis. A hospital-based descriptive cross-sectional study was conducted using 450 clinically diagnosed leptospirosis patients admitted to base and above hospitals in Monaragala district, Sri Lanka, using a pretested interviewer administered questionnaire. The patients were followed up till normal day today life after discharge. Estimation of DALYs was done using laboratory confirmed leptospirosis patients. Leptospirosis disease burden in the Monaragala district was 44.9 DALYs per 100,000 population which includes 33.18 YLLs and 10.9 YLDs. The incidence of leptospirosis in the Monaragala district during the study period was 59.8 per 100,000 population, and the case fatality rate (CFR) was 1.5% due to delay in health seeking behaviour; 75% of deaths were among males due to multi organ failure. The disease burden of leptospirosis in the Moneragala district was significantly high, and urgent efforts to control and prevent leptospirosis should be a priority.

Keywords: human leptospirosis, disease burden, disability adjusted life Years, Sri Lanka

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Authors: Nahla H. Alaswadko, Rayya A. Hassan, Bayar N. Mohammed

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Empirical deterministic models have been developed to predict roughness progression of heavy duty spray sealed pavements for a dataset representing rural arterial roads. The dataset provides a good representation of the relevant network and covers a wide range of operating and environmental conditions. A sample with a large size of historical time series data for many pavement sections has been collected and prepared for use in multilevel regression analysis. The modelling parameters include road roughness as performance parameter and traffic loading, time, initial pavement strength, reactivity level of subgrade soil, climate condition, and condition of drainage system as predictor parameters. The purpose of this paper is to report the approaches adopted for models development and validation. The study presents multilevel models that can account for the correlation among time series data of the same section and to capture the effect of unobserved variables. Study results show that the models fit the data very well. The contribution and significance of relevant influencing factors in predicting roughness progression are presented and explained. The paper concludes that the analysis approach used for developing the models confirmed their accuracy and reliability by well-fitting to the validation data.

Keywords: roughness progression, empirical model, pavement performance, heavy duty pavement

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Authors: Chang Soo Chon, Cheol Woong Ko, Han Sung Kim

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The aim of this study is to develop an anterior lumbar interbody fusion (ALIF) PEEK cage suitable for Korean people. In this study, CT images were obtained from Korean male (173cm, 71kg) and 3D Korean lumbar models were reconstructed based on the CT images to investigate anatomical characteristics. Major design parameters of anterior lumbar interbody fusion (ALIF) PEEK Cage were selected using the morphological measurement information of the Korean Lumbar models. Through finite element analysis and mechanical tests, the developed ALIF PEEK Cage prototype was compared with the Fidji Cage (Zimmer.Inc, USA) and it was found that the ALIF prototype showed similar and/or superior mechanical performance compared to the FidJi Cage. Also, clinical validation for the ALIF PEEK Cage prototype was carried out to check predictable troubles in surgical operations. Finally, it is considered that the convenience and stability of the prototype was clinically verified.

Keywords: inter-body anterior fusion, ALIF cage, PEEK, Korean lumbar, CT image, animal test

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Authors: Azadeh Moghaddas, Mehrnoush Dianatkhah, Padideh Ghaeli

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The main characteristics of borderline personality disorder (BPD) are instable regulation of affect and self-image, impulsive behavior, and lack of interpersonal relationships. Clinically, emotional dysregulation, impulsive aggression, repeated self-injury, and suicidal thought are noted with this disorder. Proper management of patients with BPD is a difficult challenge due to the complex features of this disorder. Pharmacotherapy of BPD in order to control impulsive behavior and to stabilize affect in patients with BPD has been receiving a lot of attention. Anticonvulsant agents such as topiramate, valproate, or lamotrigine, atypical antipsychotics such as aripiprazole and olanzapine and antidepressants such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors like fluvoxamine have been implicated in the treatment of BPD. Unfortunately, none of these medications can be used alone or even in combination as sole treatment of BPD. Medications may be used mostly to resolve or reduce impulsivity and aggression in these patients. Naltrexone (NTX), a nonspecific competitive opiate antagonist has been suggested, in the literature, to control self-injurious behavior (SIB) and dissociative symptoms in patients with BPD. This brief review has been intended to look at all documented evidence on the use of NTX in the management of BPD and to reach a comprehensive conclusion.

Keywords: borderline personality disorder, naltrexone, self-injurious behavior, dissociative symptoms

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Authors: J. S. Rudas, J. M. Gutiérrez Cabeza, A. Corz Rodríguez, L. M. Gómez, A. O. Toro

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The prediction of the wear rate of rubbing pairs has attracted the interest of many researchers for years. It has been recently proposed that the sliding wear rate can be inferred from the calculation of the energy rate dissipated by the tribological pair. In this paper some of the dissipative mechanisms present in a pin-on-disc configuration are discussed and both analytical and numerical calculations are carried out. Three dissipative mechanisms were studied: First, the energy release due to temperature gradients within the solid; second, the heat flow from the solid to the environment, and third, the energy loss due to abrasive damage of the surface. The Finite Element Method was used to calculate the dynamics of heat transfer within the solid, with the aid of commercial software. Validation the FEM model was assisted by virtual and laboratory experimentation using different operating points (sliding velocity and geometry contact). The materials for the experiments were Ti6Al4V alloy and Tungsten Carbide (WC-Co). The results showed that the sliding wear rate has a linear relationship with the energy dissipation flow. It was also found that energy loss due to micro-cutting is relevant for the system. This mechanism changes if the sliding velocity and pin geometry are modified though the degradation coefficient continues to present a linear behavior. We found that the less relevant dissipation mechanism for all the cases studied is the energy release by temperature gradients in the solid.

Keywords: degradation, dissipative mechanism, dry sliding, entropy, friction, wear

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Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Salako Emmanuel Adekunle

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Computer education is referred to as the knowledge and ability to use computers and related technology efficiently, with a range of skills covering levels from basic use to advance. Computer continues to make an ever-increasing impact on all aspect of human endeavours such as education. With numerous benefits of computer education, what are the insights of students on computer education? This study investigated the perception of senior secondary school students on computer education in Federal Capital Territory (FCT), Abuja, Nigeria. A sample of 7500 senior secondary schools students was involved in the study, one hundred (100) private and fifty (50) public schools within FCT. They were selected by using simple random sampling technique. A questionnaire [PSSSCEQ] was developed and validated through expert judgement and reliability co-efficient of 0.84 was obtained. It was used to gather relevant data on computer education. Findings confirmed that the students in the FCT had positive perception on computer education. Some factors were identified that affect students’ perception on computer education. The null hypotheses were tested using t-test and ANOVA statistical analyses at 0.05 level of significance. Based on these findings, some recommendations were made which include competent teachers should be employed into all secondary schools; this will help students to acquire relevant knowledge in computer education, technological supports should be provided to all secondary schools; this will help the users (students) to solve specific problems in computer education and financial supports should be provided to procure computer facilities that will enhance the teaching and the learning of computer education.

Keywords: computer education, perception, secondary school, students

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Authors: Mónica Catarina Soares

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Neoliberal rationality is currently changing the ways concepts like freedom or equality are framed. As an omnipresent and context-sensitive paradigm, homo oeconomicus is continuously taking place in realms of life previously insulated from economic and market-driven principles. This presentation is based on the argument that, more than ever, this paradigm is nowadays framing institutional and everyday discourses in regard to social problems. Although neoliberal rationality is based on the putative ideological basis that everyone is equal, equality seems to be reshaped by specific meanings apprehended by this rationality. In this sense, an illusion of equality seems to be relevant to legitimize different social inequalities (e.g., access to health care or to habitation). Political psychology has studied how ideology is relevant to legitimize market and unequal systems, but still the specific relation between markets, (in)equality and neoliberal languages is not widely addressed. The goal is to discuss the smithereens of the neoliberal rationality when it comes to legitimizing social inequalities by contesting the arguments of meritocracy, progressive freedom and minimal guarantees obeying to market-rules and principles. This analysis can be helpful to grasp for instance the continuously dismantlement of the welfare-state in different countries of the global north and how it is turning the regulation/emancipation tension inside out. The ultimate goal is to contribute to the breaking up of a paradigm that is still too big to capture, too depoliticized and chameleonic to fully acknowledge the biopolitics of power that is helping to create it.

Keywords: discourses, legitimacy, neoliberal rationality, social inequality

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Authors: Sakineh Abbasi Bourondaragh

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The aim of this research is effectiveness of integrative behavioral couples therapy on the communication patterns of couples applying for divorce. We selected (N=20) reports from Tabriz Family Judicial Complex (FJC) of couples which have conflict in their marital relationships. All of reports were released during 2012. First, they were randomly divided into two experimental and control groups and all the couples were given pre-test. They participated in twelve therapy sessions. Then the experimental group was exposed to an experimental intervention, but the control group was not received experimental intervention. The subjects were treated. At the end of treatment, a post-test was performed about subjects (each of two groups).The results showed that integrative behavioral couple therapy could increase and improve communication patterns. The findings also showed that integrative behavioral couples therapy had increased mutual constructive pattern and decreased demand/withdraw pattern and mutual avoidance pattern of CPQ sub-scale. Steady change indicator showed that the difference is clinically meaningful.

Keywords: integrative behavioral couple therapy, communication patterns, cognitive sciences, Family Judicial Complex

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Authors: Saheed O. Akinwale, Olufemi A. Koya

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Based on the need to modify palm kernel shell (PKS) and coconut shell (CNS) for some engineering applications, the study evaluated some physical characteristics and fracture resistance, relevant in estimating energy requirements in comminution of the nutshells. The shells, obtained from local processing mills, were washed, sun-dried and sorted to remove kernels, nuts and other extraneous materials. Experiments were then conducted to determine the thickness, density, moisture content, and hardness of the shells. Fracture resistances were characterised by the average compressive load, stiffness and toughness at bio-yield point of specially prepared section of the shells, under quasi-static compression loading. The densities of the dried PKS at 7.12% and the CNS at 6.47% (wb) moisture contents were 1291.20 and 1247.40 kg/m3, respectively. The corresponding Brinnel Hardness Numbers were 58.40 ± 1.91 and 56.33 ± 4.33. Close shells thickness of both PKS and CNS exhibited identical physical properties although; CNS is relatively larger in physical dimensions than PKS. The findings further showed that both shell types exhibited higher resistance with compression along the longitudinal axes than the transverse axes. With compressions along the longitudinal axes, the fracture force were 1.41 ± 0.11 and 3.62 ± 0.09 kN; bio-stiffness; 934.70 ± 67.03 kN/m and 1980.74 ± 8.92 kN/m; and toughness, 2.17 ± 0.16 and 6.51 ± 0.15 KN mm for the PKS and CNS, respectively. With the estimated toughness of CNS higher than that of PKS, the study showed the requirement of higher comminution energy for CNS.

Keywords: bio-stiffness, coconut shell, comminution, crushing strength, energy requirement, palm kernel shell, toughness

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Authors: Peregrine James Dalziel, Philip Vu Tran

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Objective / Introduction: Demand for radiology services from Emergency Departments (ED) continues to increase with greater demands placed on radiology staff providing reports for the management of complex cases. Queuing theory indicates that wide variability of process time with the random nature of request arrival increases the probability of significant queues. This can lead to delays in the time-to-availability of radiology reports (TTA-RR) and potentially impaired ED patient flow. In addition, greater “cognitive workload” of greater volume may lead to reduced productivity and increased errors. We sought to quantify the potential ED flow improvements obtainable from increased radiology providers serving 3 public hospitals in Melbourne Australia. We sought to assess the potential productivity gains, quality improvement and the cost-effectiveness of increased labor inputs. Methods & Materials: The Western Health Medical Imaging Department moved from single resident coverage on weekend days 8:30 am-10:30 pm to a limited period of 2 resident coverage 1 pm-6 pm on both weekend days. The TTA-RR for weekend CT scans was calculated from the PACs database for the 8 month period symmetrically around the date of staffing change. A multivariate linear regression model was developed to isolate the improvement in TTA-RR, between the two 4-months periods. Daily and hourly scan volume at the time of each CT scan was calculated to assess the impact of varying department workload. To assess any improvement in report quality/errors a random sample of 200 studies was assessed to compare the average number of clinically significant over-read addendums to reports between the 2 periods. Cost-effectiveness was assessed by comparing the marginal cost of additional staffing against a conservative estimate of the economic benefit of improved ED patient throughput using the Australian national insurance rebate for private ED attendance as a revenue proxy. Results: The primary resident on call and the type of scan accounted for most of the explained variability in time to report availability (R2=0.29). Increasing daily volume and hourly volume was associated with increased TTA-RR (1.5m (p<0.01) and 4.8m (p<0.01) respectively per additional scan ordered within each time frame. Reports were available 25.9 minutes sooner on average in the 4 months post-implementation of double coverage (p<0.01) with additional 23.6 minutes improvement when 2 residents were on-site concomitantly (p<0.01). The aggregate average improvement in TTA-RR was 24.8 hours per weekend day This represents the increased decision-making time available to ED physicians and potential improvement in ED bed utilisation. 5% of reports from the intervention period contained clinically significant addendums vs 7% in the single resident period but this was not statistically significant (p=0.7). The marginal cost was less than the anticipated economic benefit based assuming a 50% capture of improved TTA-RR inpatient disposition and using the lowest available national insurance rebate as a proxy for economic benefit. Conclusion: TTA-RR improved significantly during the period of increased staff availability, both during the specific period of increased staffing and throughout the day. Increased labor utilisation is cost-effective compared with the potential improved productivity for ED cases requiring CT imaging.

Keywords: workflow, quality, administration, CT, staffing

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Authors: Behrooz Nikahval, Mohammad Saeed Ahrari-Khafi, Sakineh Behroozpoor, Saeed Nazifi

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Osteoarthritis (OA) is a progressive and degenerative condition of the articular cartilage and other joints’ structures. It is essential to diagnose this condition as early as possible. The present research was performed to measure the Osteoprotegrin (OPG) and Tumor Necrosis Factor α (TNF-α) in synovial fluid and blood serum of dogs with surgically transected cruciate ligament as a model of OA, to evaluate if measuring of these parameters can be used as a way of early diagnosis of OA. In the present study, four mature, clinically healthy dogs were selected to investigate the effect of experimental OA, on OPG and TNF-α as a way of early detection of OA. OPG and TNF-α were measured in synovial fluid and blood serum on days 0, 14, 28, 90 and 180 after surgical transaction of cranial cruciate ligament in one stifle joint. Statistical analysis of the results showed that there was a significant increase in TNF-α in both synovial fluid and blood serum. OPG showed a decrease two weeks after OA induction. However, it fluctuated afterward. In conclusion, TNF-α could be used in both synovial fluid and blood serum as a way of early detection of OA; however, further research still needs to be conducted on OPG values in OA detection.

Keywords: osteoarthritis, osteoprotegrin, tumor necrosis factor α, synovial fluid, serum, dog

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Sara Vora (Hoxha)

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The present article delves into the intricate matters concerning Intellectual Property Rights (IPR) and cross-border jurisdiction within the confines of the European Union (EU). The prevalence of cross-border intellectual property rights (IPR) disputes has increased in tandem with the globalization of commerce and the widespread adoption of technology. The European Union (EU) is not immune to this trend. The manuscript presents a comprehensive analysis of various forms of intellectual property rights (IPR), such as patents, trademarks, and copyrights, and the regulatory framework established by the European Union (EU) to oversee these rights. The present article examines the diverse approaches employed for ascertaining the appropriate jurisdiction within the European Union (EU), and their potential application in the sphere of cross-border intellectual property rights (IPR) conflicts. The article sheds light on jurisdictional issues and outcomes of significant cross-border intellectual property rights (IPR) disputes in the European Union (EU). Additionally, the document provides suggestions for effectively managing intellectual property rights conflicts across borders within the European Union, which encompasses the utilization of alternative methods for resolving disputes. The article highlights the significance of comprehending the relevant jurisdiction in the European Union for Intellectual Property Rights (IPR). It also offers optimal approaches for enterprises and individuals who aim to safeguard their intellectual property beyond national boundaries. The primary objective of this article is to furnish a thorough comprehension of Intellectual Property Rights (IPR) and the relevant jurisdiction in the European Union (EU). Additionally, it endeavors to provide pragmatic recommendations for managing cross-border IPR conflicts in this intricate and ever-changing legal milieu.

Keywords: intellectual property rights (IPR), cross-border jurisdiction, applicable laws and regulations, dispute resolution, best practices

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Authors: Mahdi Rahaie

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MicroRNAs are a novel class of small RNAs which regulate gene expression by translational repression or degradation of messenger RNAs. To produce sensitive, simple and cost-effective assays for microRNAs, detection is in urgent demand due to important role of these biomolecules in progression of human disease such as Alzheimer’s, Multiple sclerosis, and some other neurodegenerative diseases. Herein, we report several novel, sensitive and specific microRNA nanobiosensors which were designed based on colorimetric and fluorescence detection of nanoparticles and hybridization chain reaction amplification as an enzyme-free amplification. These new strategies eliminate the need for enzymatic reactions, chemical changes, separation processes and sophisticated equipment whereas less limit of detection with most specify are acceptable. The important features of these methods are high sensitivity and specificity to differentiate between perfectly matched, mismatched and non-complementary target microRNAs and also decent response in the real sample analysis with blood plasma. These nanobiosensors can clinically be used not only for the early detection of neuro diseases but also for every sickness related to miRNAs by direct detection of the plasma microRNAs in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.

Keywords: hybridization chain reaction, microRNA, nanobiosensor, neurodegenerative diseases

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Authors: Viktoriia Malinovska, Iryna Kuklina, Katerina Grabicova, Milos Buric, Pavel Kozak

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Personal care products, including organic UV filters, are considered emerging contaminants and their toxic effects have been a concern for the last decades. Sunscreen compounds continually enter the surface waters via sewage water treatment due to incomplete removal and during human recreational and laundry activities. Despite the environmental occurrence of organic UV filters in the freshwater environment, little is known about their impacts on aquatic biota. In this study, environmentally relevant concentrations of 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid (BP-4, 2.5 µg/L) and 2-Phenylbenzimidazole-5-sulfonic acid (PBSA, 3 µg/L) were used to evaluate the cardiac and locomotor responses of signal crayfish Pacifastacus leniusculus during a short time period. The effects of these compounds were evident in experimental animals. Specimens exposed to both tested compounds exhibited significantly bigger changes in distance moved and time movement than controls. Significant differences in changes in mean heart rate were detected in both PBSA and BP-4 experimental groups compared to control groups. Such behavioral and physiological alterations demonstrate the ecological effects of selected sunscreen compounds during a short time period. Since the evidence of the impacts of sunscreen compounds is scarce, the knowledge of how organic UV filters influence aquatic organisms is of key importance for future research.

Keywords: aquatic pollutants, behavior, freshwaters, heart rate, invertebrate

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Authors: Amelia Faotusia

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The blue economy concept was coined by Pacific nations in recognition of the importance of sustainably managing their extensive marine territories. This is especially important for major ocean-based economic sectors of Pacific economies, such as coastal tourism. There is an absence of research, however, on the key ways in which the blue economy concept has emerged in discourse and public policy in Pacific countries, as well as how it articulates with coastal tourism. This research helps to fill such a gap with a specific focus on Tonga through the application of a post-positivist research approach to conduct a desktop study of relevant national documents and qualitative interviews with relevant government staff, civil society organizations, and tourism operators. The findings of the research reflect the importance of institutional integration and partnerships for a successful blue economy transition and are presented in the form of two case studies corresponding to two sub-sectors of Tonga’s coastal tourism sector: (i) the whale-watching and swimming industry, and (ii) beach resorts and restaurants. A thematic analysis applied to the interview data of both cases then enabled the identification of key areas and issues for socio-economic policy intervention and recommendations in support of blue economy transitions in Tonga’s coastal tourism sector. Examples of the relevant areas and issues that emerged included the importance of foreign direct investment, local market access, community-based special management areas, as well as the need to address the anthropogenic impacts of tropical cyclones, whale tourism, plastic litter on coastal assets, and ecosystems. Policy and practical interventions in support of addressing such issues include a proposed restructuring of the whale-watching and swimming licensing system; integration of climate resilience, adaptation, and capacity building as priorities of local blue economy interventions; as well as strengthening of the economic sustainability dimension of blue economy policies. Finally, this research also revealed the need for further specificity and research on the influence and value of local Tongan culture and traditional knowledge, particularly within existing customary marine tenure systems, on Tonga’s national and sectoral blue economy policies and transitions.

Keywords: blue economy, coastal tourism, integrated ocean management, ecosystem resilience

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Authors: Dong Xie, Leah Howard, Yiming Weng

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The objective of this study was to synthesize and characterize 5-acryloyloxy-3,4-dichlorocrotonolactone (a furanone derivative), use this derivative to modify a dental restorative, and study the effect of the derivative on the antibacterial activity and compressive strength of the formed restorative. In this study, a furanone derivative was synthesized, characterized, and used to formulate a dental restorative. Compressive strength (CS) and S. mutans viability were used to evaluate the mechanical strength and antibacterial activity of the formed restorative. The fabricated restorative specimens were photocured and conditioned in distilled water at 37oC for 24 h, followed by direct testing for CS or/and incubating with S. mutans for 48 h for antibacterial testing. The results show that the modified dental restorative showed a significant antibacterial activity without substantially decreasing the mechanical strengths. With addition of the antibacterial derivative up to 30%, the restorative kept its original CS nearly unchanged but showed a significant antibacterial activity with 68% reduction in the S. mutans viability. Furthermore, the antibacterial function of the modified restorative was not affected by human saliva. The aging study also indicates that the modified restorative may have a long-lasting antibacterial function. It is concluded that this experimental antibacterial restorative may potentially be developed into a clinically attractive dental filling restorative due to its high mechanical strength and antibacterial function.

Keywords: antibacterial, dental restorative, compressive strength, S. mutans viability

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Authors: Paola Comella, Vincenzo Francani, Paola Gattinoni

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This paper presents the Colzate-Vertova landslide, a Deep Seated Gravitational Slope Deformation (DSGSD) located in the Seriana Valley, Northern Italy. The paper aims at describing the development as well as evaluating the factors that influence the evolution of the landslide. After defining the conceptual model of the landslide, numerical simulations were developed using a finite element numerical model, first with a two-dimensional domain, and later with a three-dimensional one. The results of the 2-D model showed a displacement field typical of a sackung, as a consequence of the erosion along the Seriana Valley. The analysis also showed that the groundwater flow could locally affect the slope stability, bringing about a reduction in the safety factor, but without reaching failure conditions. The sensitivity analysis carried out on the strength parameters pointed out that slope failures could be reached only for relevant reduction of the geotechnical characteristics. Such a result does not fit the real conditions observed on site, where a number of small failures often develop all along the hillslope. The 3-D model gave a more comprehensive analysis of the evolution of the DSGSD, also considering the border effects. The results showed that the convex profile of the slope favors the development of displacements along the lateral valley, with a relevant reduction in the safety factor, justifying the existing landslides.

Keywords: deep seated gravitational slope deformation, Italy, landslide, numerical modeling

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Authors: Ramin Rostamkhani, Thurasamy Ramayah

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One of the most important topics of today’s industrial organizations is the challenging issue of supply chain management. In this field, scientists and researchers have published numerous practical articles and models, especially in the last decade. In this research, to our best knowledge, the discussion of data modeling of supply chain management components using well-known statistical distribution functions has been considered. The world of science owns mathematics, and showing the behavior of supply chain data based on the characteristics of statistical distribution functions is innovative research that has not been published anywhere until the moment of doing this research. In an analytical process, describing different aspects of functions including probability density, cumulative distribution, reliability, and failure function can reach the suitable statistical distribution function for each of the components of the supply chain management. It can be applied to predict the behavior data of the relevant component in the future. Providing a model to adapt the best statistical distribution function in the supply chain management components will be a big revolution in the field of the behavior of the supply chain management elements in today's industrial organizations. Demonstrating the final results of the proposed model by introducing the process capability indices before and after implementing it alongside verifying the approach through the relevant assessment as an acceptable verification is a final step. The introduced approach can save the required time and cost to achieve the organizational goals. Moreover, it can increase added value in the organization.

Keywords: analyzing, process capability indices, statistical distribution functions, supply chain management components

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Authors: Maximilian Engelhardt, Stephan Seeck

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The COVID-19 pandemic is accelerating the already growing field of e-commerce. The resulting urban freight transport volume leads to traffic and negative environmental impact. Furthermore, the service level of parcel logistics service provider is lacking far behind the expectations of consumer. These challenges can be solved by radically reorganize the urban last mile distribution structure: parcels could be consolidated in a micro hub within the inner city and delivered within time windows by cargo bike. This approach leads to a significant improvement of consumer satisfaction with their overall delivery experience. However, this approach also leads to significantly increased costs per parcel. While there is a relevant share of online shoppers that are willing to pay for such a delivery service there are no deeper insights about this target group available in the literature. Being aware of the importance of knowing target groups for businesses, the aim of this paper is to elaborate the most important factors that determine the willingness to pay for sustainable and service-oriented parcel delivery (factor analysis) and to derive customer segments (cluster analysis). In order to answer those questions, a data set is analyzed using quantitative methods of multivariate statistics. The data set was generated via an online survey in September and October 2020 within the five largest cities in Germany (n = 1.071). The data set contains socio-demographic, living-related and value-related variables, e.g. age, income, city, living situation and willingness to pay. In a prior work of the author, the data was analyzed applying descriptive and inference statistical methods that only provided limited insights regarding the above-mentioned research questions. The analysis in an exploratory way using factor and cluster analysis promise deeper insights of relevant influencing factors and segments for user behavior of the mentioned parcel delivery concept. The analysis model is built and implemented with help of the statistical software language R. The data analysis is currently performed and will be completed in December 2021. It is expected that the results will show the most relevant factors that are determining user behavior of sustainable and service-oriented parcel deliveries (e.g. age, current service experience, willingness to pay) and give deeper insights in characteristics that describe the segments that are more or less willing to pay for a better parcel delivery service. Based on the expected results, relevant implications and conclusions can be derived for startups that are about to change the way parcels are delivered: more customer-orientated by time window-delivery and parcel consolidation, more environmental-friendly by cargo bike. The results will give detailed insights regarding their target groups of parcel recipients. Further research can be conducted by exploring alternative revenue models (beyond the parcel recipient) that could compensate the additional costs, e.g. online-shops that increase their service-level or municipalities that reduce traffic on their streets.

Keywords: customer segmentation, e-commerce, last mile delivery, parcel service, urban logistics, willingness-to-pay

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