Search results for: human beta defensin 1

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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Authors: Toshitaka Higashino, Naoki Wakamiya

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Human beings perform a task by perceiving information from outside, recognizing them, and responding them. There have been various attempts to analyze and understand internal processes behind the reaction to a given stimulus by conducting psychological experiments and analysis from multiple perspectives. Among these, we focused on Model Human Processor (MHP). However, it was built based on psychological experiments and thus the relation with brain activity was unclear so far. To verify the validity of the MHP and propose our model from a viewpoint of neuroscience, EEG (Electroencephalography) measurements are performed during experiments in this study. More specifically, first, experiments were conducted where Latin alphabet characters were used as visual stimuli. In addition to response time, ERPs (event-related potentials) such as N100 and P300 were measured by using EEG. By comparing cycle time predicted by the MHP and latency of ERPs, it was found that N100, related to perception of stimuli, appeared at the end of the perceptual processor. Furthermore, by conducting an additional experiment, it was revealed that P300, related to decision making, appeared during the response decision process, not at the end. Second, by experiments using Japanese Hiragana characters, i.e. Japan's own phonetic symbols, those findings were confirmed. Finally, Japanese Kanji characters were used as more complicated visual stimuli. A Kanji character usually has several readings and several meanings. Despite the difference, a reading-related task and a meaning-related task exhibited similar results, meaning that they involved similar information processing processes of the brain. Based on those results, our model was proposed which reflects response time and ERP latency. It consists of three processors: the perception processor from an input of a stimulus to appearance of N100, the cognitive processor from N100 to P300, and the decision-action processor from P300 to response. Using our model, an application system which reflects brain activity can be established.

Keywords: brain activity, EEG, information processing model, model human processor

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Authors: Mohammadreza Judaki, Hosein Mohammadnezhad Shourkaei

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Usually, noise generated by industrial units, is a pollution and disturbs people and causes problems for human health and sometimes these units will be closed because they cannot eliminate this pollution. Small-scale power plants usually are built close to residential areas, and noise generated by these power plants is an important factor in choosing their location and their design. Materials used to reduce noise are studied by measuring their absorption and reflection index numerically and experimentally. We can use MIKI model (Yasushi Miki, 1990) to simulate absorption index by using software like Ansys or Soundflow and compare calculation results with experimental simulation data. We consider high frequency sounds of power plant engines octave band diagram because dB value of high frequency noise is more noticeable for human ears. To prove this, in this study we first will study calculating octave band of engines exhausts and then we will study acoustic behavior of materials that we will use in high frequencies and this will give us our optimum noise reduction plan.

Keywords: acoustic materials, eliminating engine noise, octave level diagram, power plant noise

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Authors: Mahmoud Ahmad Mahmoud

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The surge in unemployment among nations and the understanding of the important role played by entrepreneurship in job creation by researchers and policy makers have steered to the postulation that entrepreneurship activities can be spurred through the development of entrepreneurial intentions. Notwithstanding, entrepreneurial intention studies are very scarce in the developing world especially in the African continent. Even among the developed countries, studies of entrepreneurial intention were mostly focused on the undergraduate candidates. This paper therefore, aimed at filling the gap by employing the descriptive quantitative survey method to examine the entrepreneurial intention of 158 Nigerian postgraduate candidates of Universiti Utara Malaysia (UUM), comprising 46 Masters and 112 PhD candidates who are studying in the College of Business (COB), College of Arts and Sciences (CAS) and College of Legal, Government and International Studies (COLGIS), the theory of planned behaviour (TPB) model was used due its reputable validity, with attitudes, subjective norms and perceived behavioural control as the independent variables. Preliminary analysis and data screening were conducted which qualifies the data to the multivariate analysis assumptions. The reliability test was performed using the Cronbach Alpha method which shows all variables as reliable with a value of >0.70. However, the data is free from the multicollinearity issue with all factors in the Pearson correlation having <0.9 value and the VIF having <10. Regression analysis has shown the sufficiency and predictive capability of the TPB model to entrepreneurship intention with attitude, subjective norms and perceived behavioural control being positively and significantly related to the entrepreneurial intention of Nigerian postgraduates. Considering the Beta values, perceived behavioural control emerged as the strongest factor that influences the postgraduates entrepreneurial intention. Developing countries are therefore, recommended to make efforts in redesigning their entrepreneurship development policies to fit candidates of the highest level of academia. Further studies should replicate in a larger sample that comprises more than one university and more than one developing country.

Keywords: attitude, entrepreneurial intention, Nigeria, perceived behavioral control, postgraduates, subjective norms

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Authors: Raeesa Moolla, Ryan S. Johnson

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Air travel, and the use of airports, has experienced proliferative growth in the past few decades, resulting in the concomitant release of air pollutants. Air pollution needs to be monitored because of the known relationship between exposure to air pollutants and increased adverse effects on human health. This study monitored a group of volatile organic compounds (VOCs); specifically BTEX (viz. benzene, toluene, ethyl-benzene and xylenes), as many are detrimental to human health. Through the use of passive sampling methods, the spatial variability of BTEX within an international airport was investigated, in order to determine ‘hotspots’ where occupational exposure to BTEX may be intensified. The passive sampling campaign revealed BTEX_total concentrations ranged between 12.95–124.04 µg m^-3. Furthermore, BTEX concentrations were dispersed heterogeneously within the airport. Due to the slow wind speeds recorded (1.13 m.s^-1); the hotspots were located close to their main BTEX sources. The main hotspot was located over the main apron of the airport. Employees working in this area may be chronically exposed to these emissions, which could be potentially detrimental to their health.

Keywords: air pollution, air quality, hotspot monitoring, volatile organic compounds

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Authors: A. F. G. Van Woezik, L. M. A. Braakman-Jansen, O. A. Kulyk, J. E. W. C. Van Gemert-Pijnen

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Background: Zoonoses pose a serious threat to public health and economies worldwide, especially as antimicrobial resistance grows and newly emerging zoonoses can cause unpredictable outbreaks. In order to prevent and control emerging and re-emerging zoonoses, collaboration between veterinary, human health and public health domains is essential. In reality however, there is a lack of cooperation between these three disciplines and uncertainties exist about their tasks and responsibilities. The objective of this ongoing research project (ZonMw funded, 2014-2018) is to develop an online education and communication One Health platform, “eZoon”, for the general public and professionals working in veterinary, human health and public health domains to support the risk communication of non-alimentary zoonoses in the Netherlands. The main focus is on education and communication in times of outbreak as well as in daily non-outbreak situations. Methods: A participatory development approach was used in which stakeholders from veterinary, human health and public health domains participated. Key stakeholders were identified using business modeling techniques previously used for the design and implementation of antibiotic stewardship interventions and consisted of a literature scan, expert recommendations, and snowball sampling. We used a stakeholder salience approach to rank stakeholders according to their power, legitimacy, and urgency. Semi-structured interviews were conducted with stakeholders (N=20) from all three disciplines to identify current problems in risk communication and stakeholder values for the One Health platform. Interviews were transcribed verbatim and coded inductively by two researchers. Results: The following key values were identified (but were not limited to): (a) need for improved awareness of veterinary and human health of each other’s fields, (b) information exchange between veterinary and human health, in particularly at a regional level; (c) legal regulations need to match with daily practice; (d) professionals and general public need to be addressed separately using tailored language and information; (e) information needs to be of value to professionals (relevant, important, accurate, and have financial or other important consequences if ignored) in order to be picked up; and (f) need for accurate information from trustworthy, centrally organised sources to inform the general public. Conclusion: By applying a participatory development approach, we gained insights from multiple perspectives into the main problems of current risk communication strategies in the Netherlands and stakeholder values. Next, we will continue the iterative development of the One Health platform by presenting key values to stakeholders for validation and ranking, which will guide further development. We will develop a communication platform with a serious game in which professionals at the regional level will be trained in shared decision making in time-critical outbreak situations, a smart Question & Answer (Q&A) system for the general public tailored towards different user profiles, and social media to inform the general public adequately during outbreaks.

Keywords: ehealth, one health, risk communication, stakeholder, zoonosis

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Nipawan Tharasak, Ladda Hirunyava

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The objective of the research was to study factors affecting working efficiency and the relationship between working environment, satisfaction to human resources management and operation employees’ working efficiency of Faculty of Management Science, Suan Sunandha Rajabhat University. The sample size of the research was based on 33 employees of Faculty of Management Science. The researcher had classified the support employees into 4 divisions by using Stratified Random Sampling. Individual sample was randomized by using Simple Random Sampling. Data was collected through the instrument. The Statistical Package for the Windows was utilized for data processing. Percentage, mean, standard deviation, the t-test, One-way ANOVA, and Pearson product moment correlation coefficient were applied. The result found the support employees’ satisfaction in human resources management of Faculty of Management Science in following areas: remuneration; employee recruitment & selection; manpower planning; performance evaluation; staff training & developing; and spirit & fairness were overall in good level.

Keywords: faculty of management science, operational factors, practice performance, staff working

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Authors: Eman Alarfaj, Hissah Alabdullatif, Huda Alabdullatif, Ghazal Albakri, Nor Shahriza Abdul Karim

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Autism Spectrum Disorder is extensively spread amid children; it affects their social, communication and interactive skills. As robotics technology has been proven to be a significant helpful utility those able individuals to overcome their disabilities. Robotic technology is used in ASD therapy. The purpose of this research is to show how Nao robots can improve the social skills for children who suffer from autism in Saudi Arabia by interacting with the autistic child and perform a number of tasks. The objective of this research is to identify, implement, and test the effectiveness of the module for interacting with ASD children in an autism center in Saudi Arabia. The methodology in this study followed the ten layers of protocol that needs to be followed during any human-robot interaction. Also, in order to elicit the scenario module, TEACCH Autism Program was adopted. Six different qualified interaction modules have been elicited and designed in this study; the robot will be programmed to perform these modules in a series of controlled interaction sessions with the Autistic children to enhance their social skills.

Keywords: humanoid robot Nao, ASD, human-robot interaction, social skills

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Authors: Ahlem Setrallah

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Environment has become a phenomenon directly linked to security in recent decades. This security aspect of environment is justified by the challenges that environment problems can have on human life and thus security especially within the scope of human security that is based mainly on the individual rather than on the state. Because Africa is not safe from the global warming and all its consequences on environment, this continent has witnessed many crises related to environment and that have had direct impact on security in Africa. One of those crises is environmental displacement or immigration which was caused by natural disasters like draught, desertification and food shortage to name but a few. This paper aims at shedding light at some important cases in the Africa focusing mainly on the Sahel region. The main research questions that we are trying to answer are the following: 1-What is the relationship between environment and forced immigration in the Sahel region? 2-What is the impact of environmental immigration on Security in the region? 3-How have the states in this region reacted to this crisis? 4-Is the measures taken by those states adequate or not? 5- How to remedy for the limitations of those measures? The paper is based on case study methodology as a way to better understand the relationship between security and environment using library research for data collection and analysis. This paper aims also at presenting some suggesting regarding possible ways of reducing the negative impact of environmental immigration.

Keywords: environment, refugees, Sahel region, security

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Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy

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Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization

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Authors: Gianni Izzo

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The relation of Islam to its legal precepts, reflected in the various jurisprudential 'schools of thought' (madhahib), is one expressed in a version of 'positivism' (fiqh) providing the primary theory for deducing Qurʾan rulings and those from the narrations (hadith) of the Prophet Muhammad. Scholars of Islam, including Patricia Crone (2004) and others chronicled by Anver Emon (2005), deny the influence of natural law theories as extra-scriptural indices of revelation’s content. This paper seeks to dispute these claims by reference to historical and canonical examples within Shiʿa legal thought that emphasize the salient roles of ‘aql (reason), fitrah (primordial human nature), and lutf (divine grace). These three holistic features, congenital to every human, and theophanically reflected in nature make up a mode of moral intelligibility antecedent to prophetic revelation. The debate between the 'traditionalist' Akhbaris and 'rationalist' Usulis over the nature of deriving legal edicts in Islam is well-covered academic ground. Instead, an attempt is made to define and detail the built-in assumptions of natural law revealed in the jurisprudential summa of Imami Shiʿism, whether of either dominant school, that undergird its legal prescriptions and methods of deduction.

Keywords: Islam, fiqh, natural law, legal positivism, aql

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Adam J. Bowen

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Abstract— Should robots have rights or legal protections. Often debates concerning whether robots and AI should be afforded rights focus on conditions of personhood and the possibility of future advanced forms of AI satisfying particular intrinsic cognitive and moral attributes of rights-holding persons. Such discussions raise compelling questions about machine consciousness, autonomy, and value alignment with human interests. Although these are important theoretical concerns, especially from a future design perspective, they provide limited guidance for addressing the moral and legal standing of current and near-term AI that operate well below the cognitive and moral agency of human persons. Robots and AI are already being pressed into service in a wide range of roles, especially in healthcare and biomedical contexts. The design and large-scale implementation of robots in the context of core societal institutions like healthcare systems continues to rapidly develop. For example, we bring them into our homes, hospitals, and other care facilities to assist in care for the sick, disabled, elderly, children, or otherwise vulnerable persons. We enlist surgical robotic systems in precision tasks, albeit still human-in-the-loop technology controlled by surgeons. We also entrust them with social roles involving companionship and even assisting in intimate caregiving tasks (e.g., bathing, feeding, turning, medicine administration, monitoring, transporting). There have been advances to enable severely disabled persons to use robots to feed themselves or pilot robot avatars to work in service industries. As the applications for near-term AI increase and the roles of robots in restructuring our biomedical practices expand, we face pressing questions about the normative implications of human-robot interactions and collaborations in our collective worldmaking, as well as the moral and legal status of robots. This paper argues that robots operating in public and private spaces be afforded some protections as either moral patients or legal agents to establish prohibitions on robot abuse, misuse, and mistreatment. We already implement robots and embed them in our practices and institutions, which generates a host of human-to-machine and machine-to-machine relationships. As we interact with machines, whether in service contexts, medical assistance, or home health companions, these robots are first encountered in relationship to us and our respective roles in the encounter (e.g., surgeon, physical or occupational therapist, recipient of care, patient’s family, healthcare professional, stakeholder). This proposal aims to outline a framework for establishing limiting factors and determining the extent of moral or legal protections for robots. In doing so, it advocates for a relational approach that emphasizes the priority of mapping the complex contextually sensitive roles played and the relations in which humans and robots stand to guide policy determinations by relevant institutions and authorities. The relational approach must also be technically informed by the intended uses of the biomedical technologies in question, Design History Files, extensive risk assessments and hazard analyses, as well as use case social impact assessments.

Keywords: biomedical robots, robot ethics, robot laws, human-robot interaction

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Authors: Mohsen Davarzani, Ehsan Lame, Mohammad Taghi Hassan Zadeh

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Language is considered as a powerful and outstanding feature of ethnicity. However, humiliating and prohibiting using human language is one the most heinous and brutal acts in the form of racism. In other words, racism can be a product of physiological humiliations and discrimination, such as skin color, and can also be resulted from ethnic humiliation and discrimination such as language, customs and so on. Ethnic and racial discrimination is one of the main problems of the world that minorities and occasionally the majority have suffered from. Nowadays, few states can be found in which all individuals and its citizens are of the same race and ethnicity, culture and language. In these countries, referred to as the multinational states, (eg, Iran, Switzerland, India, etc.), there are the communities and groups which have their own linguistic, cultural and historical characteristics. Characteristics of human rights issues, diversity of issues and plurality of meanings indicate that they appear in various aspects. The states are obliged to respect, as per national and international obligations, the rights of all citizens from different angles, especially different groups that require special attention in order of the particular aspects such as ethnicity, religious and political minorities, children, women, workers, unions and in case the states are in breach of any of these items, they are faced with challenges in local, regional or international fields.

Keywords: law, language, minorities, ethnicity

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Authors: Eszter J. Tóth, Alexandra Hoffmann, Csaba Vágvölgyi, Tamás Papp

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Members of the genera Curvularia and Bipolaris are closely related melanin producing filamentous fungi; both of them have the teleomorph states in genus Cochliobolus. While Bipolaris species infect only plants and may cause serious agriculture damages, some Curvularia species was recovered from opportunistic human infections. The human pathogenic species typically cause phaeohyphomycoses, i.e. mould infections caused by melanised fungi, which can manifest as invasive mycoses with frequent involvement of the central nervous system in immunocompromised patients or as local infections (e.g. keratitis, sinusitis, and cutaneous lesions) in immunocompetent people. Although their plant-fungal interactions have been intensively studied, there is only little information available about the human pathogenic feature of these fungi. The aim of this study was to investigate the neutrophil granulocytes’ response to hyphal forms of Curvularia and Bipolaris in comparison with the response to Aspergillus. In the present study Curvularia lunata SZMC 23759 and Aspergillus fumigatus SZMC 23245 both isolated from human eye infection, and Bipolaris zeicola BRIP 19582b isolated from plant leaf were examined. Neutrophils were isolated from heparinised venous blood of healthy donors with dextran sedimentation followed by centrifugation over Ficoll and hypotonic lysis of erythrocytes. Viability and purity of the cells were checked with trypan blue and Wright staining, respectively. Infection of neutrophils was carried out with germinated conidia in a ratio of 5:1. Production of hydrogen peroxide, superoxide anion, and nitrogen monoxide was measured both intracellularly and extracellularly in response to the germinated spores with or without the supernatant and after serum treatment. ROS and NOS production of neutrophils in interaction with the three fungi were compared. It is already known that Aspergillus species induce ROS production of neutrophils only after serum treatment. Although, in case of C. lunata, serum opsonisation also induced an intensive production of reactive species, lower level of production was measured in the lack of serum as well. After interaction with the plant pathogenic B. zeicola, amount of reactive species found to be similar with and without serum treatment. The presence of germination supernatant decreased the reactive species production in case of each fungus. Interaction with Curvularia, Bipolaris and Aspergillus species induced different response of neutrophils. It seems that recognition of C. lunata and B. zeicola is independent of serum opsonisation, albeit it increases the level of the produced reactive species in response for C. lunata. The study was supported by the grant LP2016-8/2016.

Keywords: Curvularia, neutrophils, NOS, ROS, serum opsonisation

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Jean Marie Ntaganda, Froduald Minani, Wellars Banzi, Lydie Mpinganzima, Japhet Niyobuhungiro, Jean Bosco Gahutu, Vincent Dusabejambo, Immaculate Kambutse

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In this paper, we present a nonlinear dynamic model for the interactive mechanism of the cardiovascular and respiratory system. The model is designed and analyzed for human during physical exercises. In order to verify the adequacy of the designed model, data collected in Rwanda are used for validation. We have simulated the impact of heart rate and alveolar ventilation as controls of cardiovascular and respiratory system respectively to steady state response of the main cardiovascular hemodynamic quantities i.e., systemic arterial and venous blood pressures, arterial oxygen partial pressure and arterial carbon dioxide partial pressure, to the stabilised values of controls. We used data collected in Rwanda for both male and female during physical activities. We obtained a good agreement with physiological data in the literature. The model may represent an important tool to improve the understanding of exercise physiology.

Keywords: exercise, cardiovascular/respiratory, hemodynamic quantities, numerical simulation, physical activity, sportsmen in Rwanda, system

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Authors: Milind Bharambe, Chander Shekhar

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India is a vast country with its 1.21 billion population at the dawn of new decade, which accounts for one sixth of the global human capital in the world today. It is well known that health expenditure in India is dominated by private spending. This is an unfortunate consequence of India’s development because of large positive externality associated with health spending, which make health a merit good. This paper has used data from NSSO and Indian Government’s spending on health as reported by Ministry of Health and Family Welfare. Understanding of the dynamism of age-structure of the population would greatly optimize the expenditure on health care services. A country with good public health indicators is bound to possess good human capital which is an asset to the economic growth and indicator of development status of country. The paper tries to present the linkages between the health expenditure incurred by different states at various levels of demographic transition levels and the efficiency in utilization of health expenditure. It also looks into the way in which allocative efficiency health services can be improved. Paper tries to explore the per capita spending on health and how the demographic transition taking place in different states of India affect the required quantity and quality of health services.

Keywords: age structure, demographic transition, health expenditure, morbidity

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Authors: Kashika P. H.

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The development of computer vision systems has been greatly aided by the efficient and precise detection of images and videos. Although the ability to recognize and comprehend images is a strength of the human brain, employing technology to tackle this issue is exceedingly challenging. In the past few years, the use of Deep Learning algorithms to treat object detection has dramatically expanded. One of the key issues in the realm of image recognition is the recognition and detection of certain notable people from randomly acquired photographs. Face recognition uses a way to identify, assess, and compare faces for a variety of purposes, including user identification, user counting, and classification. With the aid of an accessible deep learning-based API, this article intends to recognize various faces of people and their facial descriptors more accurately. The purpose of this study is to locate suitable individuals and deliver accurate information about them by using the Amazon Rekognition system to identify a specific human from a vast image dataset. We have chosen the Amazon Rekognition system, which allows for more accurate face analysis, face comparison, and face search, to tackle this difficulty.

Keywords: Amazon rekognition, API, deep learning, computer vision, face detection, text detection

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Authors: Masbubul Ishtiaque Ahmed

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Food chain contamination by heavy metals has become a critical issue in recent years because of their potential accumulation in bio systems through contaminated water, soil and irrigation water. Industrial discharge, fertilizers, contaminated irrigation water, fossil fuels, sewage sludge and municipality wastes are the major sources of heavy metal contamination in soils and subsequent uptake by crops. The main objectives of this project were to determine the levels of minerals, trace elements and heavy metals in major foods and beverages consumed by the poor and non-poor households of Dhaka city and assess the dietary risk exposure to heavy metal and trace metal contamination and potential health implications as well as recommendations for action. Heavy metals are naturally occurring elements that have a high atomic weight and a density of at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, and carcinogenicity.

Keywords: food chain, determine the levels of minerals, trace elements, heavy metals, production and use, human exposure, toxicity, carcinogenicity

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Authors: Morteza Maleki

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In the present study is that it tried to behave in the environment to be monitored and the respective roles of environment (assumed as a vessel) and human beings (assumed as occupants of this vessel) inevitably create effects which can be expressed as various behaviors on the part of human being. The mutual relationship between man and his environment is exhibited through perceptions, behaviors, subjective images, activities, etc. This study investigates the conceptual dimension in the form of the four components of readability, sense of place, identity, and Tenability (tenability) at the Ahmadabad Axis in Mashhad. The theoretical fundamentals and the data regarding the status quo were presented through the descriptive method and the proposed policies were derived through analyzing the available status quo information. The required data were gathered from library resources and documents related to the studied area as well as from instruments used in field methods such as questionnaires. Upon conducting the necessary investigation, the conceptual dimension within the design area was analyzed. The SWOT table was presented, and the results obtained for improving environmental perception were arranged in the form of policy-making tables and operational projects tables for improving the sense of place, creating imagery, and other investigated components.

Keywords: public space, perception, environment, behavior

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Authors: Lowanika Victor Tibane, David Mamba

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Human body, animals, and plants depend on certain essential metals in permissible quantities for their survival. Excessive metal concentration may cause severe malfunctioning of the organisms and even fatal in extreme cases. Because of gold mining in the Witwatersrand basin in South Africa, enormous untreated mine dumps comprise elevated concentration of essential trace elements. Elevated quantities of trace metal have direct negative impact on the quality of soil for different land use types, reduce soil efficiency for plant growth, and affect the health human and animals. A total of 21 subsoil samples were examined using inductively coupled plasma optical emission spectrometry and X-ray fluorescence methods and the results elevated men concentration of Fe (36,433.39) > S (5,071.83) > Cu (1,717,28) > Mn (612.81) > Cr (74.52) > Zn (68.67) > Ni (40.44) > Co (9.63) > P (3.49) > Mo > (2.74), reported in mg/kg. Using various contamination indices, it was discovered that the sites surveyed are on average moderately contaminated with Co, Cr, Cu, Mn, Ni, S, and Zn. The ecological risk assessment revealed a low ecological risk for Cr, Ni and Zn, whereas Cu poses a very high ecological risk.

Keywords: essential trace elements, soil contamination, contamination indices, toxicity, descriptive statistics, ecological risk evaluation

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Authors: M. G. Cattaneo

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The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

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Authors: Abdelhadi Adel, Kadri Ouahab

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This paper proposes a hybrid algorithm for the integration of systematic preventive maintenance policies in hybrid flow shop scheduling to minimize makespan. We have implemented a problem-solving approach for optimizing the processing time, methods based on metaheuristics. The proposed approach is inspired by the behavior of the human body. This hybridization is between a multi-agent system and inspirations of the human body, especially genetics. The effectiveness of our approach has been demonstrated repeatedly in this paper. To solve such a complex problem, we proposed an approach which we have used advanced operators such as uniform crossover set and single point mutation. The proposed approach is applied to three preventive maintenance policies. These policies are intended to maximize the availability or to maintain a minimum level of reliability during the production chain. The results show that our algorithm outperforms existing algorithms. We assumed that the machines might be unavailable periodically during the production scheduling.

Keywords: multi-agent systems, emergence, genetic algorithm, makespan, systematic maintenance, scheduling, hybrid flow shop scheduling

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Authors: Shokoufeh Abrisham, Seyed Mahmoud Hossieni, Elham Pishbin

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In this paper, a hybrid method based on the fault tree analysis (FTA) and Bayesian networks (BNs) are employed to evaluate the team performance quality of advanced cardiac life support (ACLS) procedures in emergency department. According to American Heart Association (AHA) guidelines, a category relying on staff action leading to clinical incidents and also some discussions with emergency medicine experts, a fault tree model for ACLS procedure is obtained based on the human performance. The obtained FTA model is converted into BNs, and some different scenarios are defined to demonstrate the efficiency and flexibility of the presented model of BNs. Also, a sensitivity analysis is conducted to indicate the effects of team leader presence and uncertainty knowledge of experts on the quality of ACLS. The proposed model based on BNs shows that how the results of risk analysis can be closed to reality comparing to the obtained results based on only FTA in medical procedures.

Keywords: advanced cardiac life support, fault tree analysis, Bayesian belief networks, numan performance, healthcare systems

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Sangbaek Park, Seungju Lee, Soo-Won Chae

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Unstable shoes are known to strengthen lower extremity muscles and improve gait ability and to change the user’s gait pattern. The change in gait pattern affects human body enormously because the walking is repetitive and steady locomotion in daily life. It is possible to estimate the joint motion including joint moment, force and inertia effect using kinematic and kinetic analysis. However, the change of internal stress at the articular cartilage has not been possible to estimate. The purpose of this research is to evaluate the internal stress of human body during gait with unstable shoes. In this study, FE analysis was combined with motion capture experiment to obtain the boundary condition and loading condition during walking. Motion capture experiments were performed with a participant during walking with normal shoes and with unstable shoes. Inverse kinematics and inverse kinetic analysis was performed with OpenSim. The joint angle and muscle forces were estimated as results of inverse kinematics and kinetics analysis. A detailed finite element (FE) lower extremity model was constructed. The joint coordinate system was added to the FE model and the joint coordinate system was coincided with OpenSim model’s coordinate system. Finally, the joint angles at each phase of gait were used to transform the FE model’s posture according to actual posture from motion capture. The FE model was transformed into the postures of three major phases (1st peak of ground reaction force, mid stance and 2nd peak of ground reaction force). The direction and magnitude of muscle force were estimated by OpenSim and were applied to the FE model’s attachment point of each muscle. Then FE analysis was performed to compare the stress at knee cartilage during gait with normal shoes and unstable shoes.

Keywords: finite element analysis, gait analysis, human model, motion capture

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Authors: Alejandra Cardenas, Ona Flores, Fabiola Gretzinger

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Since the 1990s, legal strategies for the promotion and protection of maternal health rights have achieved significant gains. Successful litigation in courts around the world have shown that these rights can be judicially enforceable. Governments and international organizations have acknowledged the importance of a human rights-based approach to maternal mortality and morbidity, and obstetric violence has been recognized as a human rights issue. Despite the progress made, maternal mortality has worsened in some regions of the world, while progress has stagnated elsewhere, and mistreatment in maternal care is reported almost universally. In this context, issues of maternal autonomy and decision-making during pregnancy, labor, and delivery as a critical barrier to access quality maternal health have been largely overlooked. Indeed, despite the principles of autonomy and informed consent in medical interventions being well-established in international and regional norms, how they are applied particularly during childbirth and pregnancy remains underdeveloped. National and global legal standards and decisions related to maternal health were reviewed and analyzed to determine how maternal autonomy and decision-making during pregnancy, labor, and delivery have been protected (or not) by international and national courts. The results of this legal research and analysis lead to the conclusion that a few standards have been set by courts regarding pregnant people’s rights to make choices during pregnancy and birth; however, most undermine the agency of pregnant people. These decisions recognize obstetric violence and gender-based discrimination, but fail to protect pregnant people’s autonomy, privacy, and their right to informed consent. As current human rights standards stand today, maternal health is the only field in medicine and law in which informed consent can be overridden, and patients can be forced to submit to treatments against their will. Unconsented treatment and loss of agency during pregnancy and childbirth can have long-term physical and mental impacts, reduce satisfaction and trust in health systems, and may deter future health-seeking behaviors. This research proposes a path forward that focuses on the pregnant person as an independent agent, relying on the doctrine of self-determination during pregnancy and childbirth, which includes access to the necessary conditions to enable autonomy and choice throughout pregnancy and childbirth as a critical step towards our approaches to reduce maternal mortality, morbidity, and mistreatment, and realize the promise of access to quality maternal health as a human right.

Keywords: autonomy in childbirth and pregnancy, choice, informed consent, jurisprudential analysis

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Authors: Marcel Chevalier, Léo Dupont, Sylvain Marié, Frédérique Roffet, Elena Stolyarova, William Templier, Costin Vasile

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Industrial end-users are currently facing an increasing need to reduce the risk of unexpected failures and optimize their maintenance. This calls for both short-term analysis and long-term ageing anticipation. At Schneider Electric, we tackle those two issues using both machine learning and first principles models. Machine learning models are incrementally trained from normal data to predict expected values and detect statistically significant short-term deviations. Ageing models are constructed by breaking down physical systems into sub-assemblies, then determining relevant degradation modes and associating each one to the right kinetic law. Validating such anomaly detection and maintenance models is challenging, both because actual incident and ageing data are rare and distorted by human interventions, and incremental learning depends on human feedback. To overcome these difficulties, we propose to simulate physics, systems, and humans -including asset maintenance operations- in order to validate the overall approaches in accelerated time and possibly choose between algorithmic alternatives.

Keywords: degradation models, ageing, anomaly detection, soft sensor, incremental learning

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