Search results for: clinical advice services

Authors: Cristina Maria Mendoza Sanchez, Maria Angeles Navarro Perán

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Introduction: Nursing as a profession, from its initial formation and after its development in practice, has been built and identified mainly from its technical competence and professionalization within the positivist approach of the XIX century that provides a conception of the disease built on the basis of to the biomedical paradigm, where the care provided is more focused on the physiological processes and the disease than on the suffering person understood as a whole. The main issue that is in need of study here is a review of the nursing profession's history to get to know how the nursing profession was before the XIX century. It is unclear if there were organizations or people with knowledge about looking after others or if many people survived by chance. The holistic care, in which the appearance of the disease directly affects all its dimensions: physical, emotional, cognitive, social and spiritual. It is not a concept from the 21st century. It is common practice, most probably since established life in this world, with the final purpose of covering all these perspectives through quality care. Objective: In this paper, we describe and analyze the history of education in nursing learning in terms of reviewing and analysing theoretical foundations of clinical teaching and learning in nursing, with the final purpose of determining and describing the development of the nursing profession along the history. Method: We have done a descriptive systematic review study, doing a systematically searched of manuscripts and articles in the following health science databases: Pubmed, Scopus, Web of Science, Temperamentvm and CINAHL. The selection of articles has been made according to PRISMA criteria, doing a critical reading of the full text using the CASPe method. A compliment to this, we have read a range of historical and contemporary sources to support the review, such as manuals of Florence Nightingale and John of God as primary manuscripts to establish the origin of modern nursing and her professionalization. We have considered and applied ethical considerations of data processing. Results: After applying inclusion and exclusion criteria in our search, in Pubmed, Scopus, Web of Science, Temperamentvm and CINAHL, we have obtained 51 research articles. We have analyzed them in such a way that we have distinguished them by year of publication and the type of study. With the articles obtained, we can see the importance of our background as a profession before modern times in public health and as a review of our past to face challenges in the near future. Discussion: The important influence of key figures other than Nightingale has been overlooked and it emerges that nursing management and development of the professional body has a longer and more complex history than is generally accepted. Conclusions: There is a paucity of studies on the subject of the review to be able to extract very precise evidence and recommendations about nursing before modern times. But even so, as more representative data, an increase in research about nursing history has been observed. In light of the aspects analyzed, the need for new research in the history of nursing emerges from this perspective; in order to germinate studies of the historical construction of care before the XIX century and theories created then. We can assure that pieces of knowledge and ways of care were taught before the XIX century, but they were not called theories, as these concepts were created in modern times.

Keywords: nursing history, nursing theory, Saint John of God, Florence Nightingale, learning, nursing education

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Authors: Ali Aqa Mohammad Jawad

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Taking a relational approach, this paper analyzes the causal mechanisms associated with successful mobilization and rapid demobilization of the Enlightening Movement in post-2001 Afghanistan. The movement emerged after the state-owned Da Afghan Bereshna Sherkat (DABS) decided to divert the route for the Turkmenistan-Uzbekistan-Tajikistan-Afghanistan-Pakistan (TUTAP) electricity project. The grid was initially planned to go through the Hazara-inhabited province of Bamiyan, according to Afghanistan’s Power Sector Master Plan. The reroute served as an aide-mémoire of historical subordination to other ethno-religious groups for the Hazara community. It was also perceived as deprivation from post-2001 development projects, financed by international aid. This torched the accumulated grievances, which then gave birth to the Enlightening Movement. The movement had a successful mobilization. However, it demobilized after losing much of its mobilizing capabilities through an amalgamation of external and internal relational factors. The successful mobilization yet rapid demobilization constitutes the puzzle of this paper. From the theoretical perspective, this paper is significant as it establishes the applicability of contentious politics theory to protest mobilizations that occurred in Afghanistan, a context-specific, characterized by ethnic politics. Both primary and secondary data are utilized to address the puzzle. As for the primary resources, media coverage, interviews, reports, public media statements of the movement, involved in contentious performances, and data from Social Networking Services (SNS) are used. The covered period is from 2001-2018. As for the secondary resources, published academic articles and books are used to give a historical account of contentious politics. For data analysis, a qualitative comparative historical method is utilized to uncover the causal mechanisms associated with successful mobilization and rapid demobilization of the Movement. In this pursuit, both mobilization and demobilization are considered as larger political processes that could be decomposed to constituent mechanisms. Enlightening Movement’s framing and campaigns are first studied to uncover the associated mechanisms. Then, to avoid introducing some ad hoc mechanisms, the recurrence of mechanisms is checked against another case. Mechanisms qualify as robust if they are “recurrent” in different episodes of contention. Checking the recurrence of causal mechanisms is vital as past contentious events tend to reinforce future events. The findings of this paper suggest that the public sphere in Afghanistan is drastically different from Western democracies known as the birthplace of social movements. In Western democracies, when institutional politics did not respond, movement organizers occupied the public sphere, undermining the legitimacy of the government. In Afghanistan, the public sphere is ethicized. Considering the inter- and intra-relational dynamics of ethnic groups in Afghanistan, the movement reduced to an erosive inter- and intra-ethnic conflict. This undermined the cohesiveness of the movement, which then kicked-off its demobilization process.

Keywords: enlightening movement, contentious politics, mobilization, demobilization

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Authors: Maria M. Calheiros, Carla Silva, Eunice Magalhães

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Professionals working in child protection services (CPS) need to have common and clear criteria to identify cases of maltreatment and to differentiate levels of severity in order to determine when CPS intervention is required, its nature and urgency, and, in most countries, the service that will be in charge of the case (community or specialized CPS). Actually, decision-making process is complex in CPS, and, for that reason, such criteria are particularly important for who significantly contribute to that decision-making in child maltreatment cases. The main objective of this presentation is to describe the Maltreatment Severity Assessment Questionnaire (MSQ), specifically designed to be used by professionals in the CPS, which adopts a multidimensional approach and uses a scale of severity within subtypes. Specifically, we aim to provide evidence of validity and reliability of this tool, in order to improve the quality and validity of assessment processes and, consequently, the decision making in CPS. The total sample was composed of 1000 children and/or adolescents (51.1% boys), aged between 0 and 18 years old (M = 9.47; DP = 4.51). All the participants were referred to official institutions of the children and youth protective system. Children and adolescents maltreatment (abuse, neglect experiences and sexual abuse) were assessed with 21 items of the Maltreatment Severity Questionnaire (MSQ), by professionals of CPS. Each item (sub-type) was composed of four descriptors of increasing severity. Professionals rated the level of severity, using a 4-point scale (1= minimally severe; 2= moderately severe; 3= highly severe; 4= extremely severe). The construct validity of the Maltreatment Severity Questionnaire was assessed with a holdout method, performing an Exploratory Factor Analysis (EFA) followed by a Confirmatory Factor Analysis (CFA). The final solution comprised 18 items organized in three factors 47.3% of variance explained. ‘Physical neglect’ (eight items) was defined by parental omissions concerning the insurance and monitoring of the child’s physical well-being and health, namely in terms of clothing, hygiene, housing conditions and contextual environmental security. ‘Physical and Psychological Abuse’ (four items) described abusive physical and psychological actions, namely, coercive/punitive disciplinary methods, physically violent methods or verbal interactions that offend and denigrate the child, with the potential to disrupt psychological attributes (e.g., self-esteem). ‘Psychological neglect’ (six items) involved omissions related to children emotional development, mental health monitoring, school attendance, development needs, as well as inappropriate relationship patterns with attachment figures. Results indicated a good reliability of all the factors. The assessment of child maltreatment cases with MSQ could have a set of practical and research implications: a) It is a valid and reliable multidimensional instrument to measure child maltreatment, b) It is an instrument integrating the co-occurrence of various types of maltreatment and a within-subtypes scale of severity; c) Specifically designed for professionals, it may assist them in decision-making processes; d) More than using case file reports to evaluate maltreatment experiences, researchers could guide more appropriately their research about determinants and consequences of maltreatment.

Keywords: assessment, maltreatment, children and youth, decision-making

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Authors: José Antonio Donaire Benito, Konstantina Zerva

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Historically, cities have been places where people from many nations and cultures have met and settled together, while population flows and density have had a significant impact on urban dynamics. Cities' high density of social, cultural, business offerings, everyday services, and other amenities not intended for tourists draw not only tourists but a wide range of city users as well. With the coordination of city rhythms and the porosity of the community, city users order and frame their urban experience. From one side, recent literature focuses on the shift in urban tourist experience from 'having' a holiday through 'doing' activities to 'becoming' a local by experiencing a part of daily life. On the other hand, there is a debate on the 'touristification of everyday life', where middle and upper class urban dwellers display attitudes and behaviors that are virtually undistinguishable from those of visitors. With the advent of globalization and technological advances, modern society has undergone a radical transformation that has altered mobility patterns within it, blurring the boundaries between tourism and everyday life, work and leisure, and "hosts" and "guests". Additionally, the presence of other 'temporary city' users, such as commuters, digital nomads, second home owners, and migrants, contributes to a more complex transformation of tourist cities. Moving away from this traditional clear distinction between 'hosts' and 'guests', which represents a more static view of tourism, and moving towards a more liquid narrative of mobility, academics on tourism development are embracing the New Mobilities Paradigm. The latter moves beyond the static structures of the modern world and focuses on the ways in which social entities are made up of people, machines, information, and images in a moving system. In light of this fluid interdependence between tourists and guests, a question arises as to whether overtourism, which is considered as the underlying cause of citizens' perception of a lower urban quality of life, is a fair representation of perceived mobility excessiveness, place consumption disruptiveness, and residents displacement. As a representative example of an overtourism narrative, Barcelona was chosen as a study area for this purpose, focusing on the incoming city users to reflect in depth the variety of people who contribute to mobility flows beyond those residents already have. Several statistical data have been analyzed to determine the number of national and international visitors to Barcelona at some point during the day in 2019. Specifically, tracking data gathered from mobile phone users within the city are combined with tourist surveys, urban mobility data, zenithal data capture, and information about the city's attractions. The paper shows that tourists are only a small part of the different incoming city users that daily enter Barcelona; excursionists, commuters, and metropolitans also contribute to a high mobility flow. Based on the diversity of incoming city users and their place consumption, it seems that the city's urban experience is more likely to be impacted by over-mobility tan over-tourism.

Keywords: city users, density, new mobilities paradigm, over-tourism.

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Authors: Carlu Van Der Westhuizen

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The South African Agricultural Sector is of major socio-economic importance to the country due to its contribution in maintaining stability in food production and food security, providing labour opportunities, eradicating poverty and earning foreign currency. Against this reality, this paper investigates within the Agricultural Sector in South Africa the changes in Land Policies that the new democratically elected government (African National Congress) brought about since their takeover in 1994. The change in the agricultural environment is decidedly dualistic, with 1) a commercial sector, and 2) a subsistence and emerging farmer sector. The future demands and challenges are mostly identified as those of land redistribution and social upliftment. Opportunities that arose from the challenge of change are, among others, the small-holder participation in the value chain, while the challenge of change in Agriculture and the opportunities that were identified could serve as a yardstick against which the Sectors’ (Agriculture) Performance could be measured in future. Unfortunately, despite all Governments’ Policies, Programmes and Projects and inputs of the Private Sector, the outcomes are, to a large extend, unsuccessful. The urgency with the Land Redistribution Programme is that, for the period 1994 – 2014, only 7.5% of the 30% aim in the redistribution of land was achieved. Another serious aspect of concern is that 90% of the Land Redistribution Projects are not in a state of productive use by emerging farmers. Several reasons may be offered for these failures, amongst others the uncoordinated way in which different stakeholders are involved in a specific farming project. These stakeholders could generally in most cases be identified as: - The Government as the policy maker; - The Private Sector that has the potential to contribute to the sustainable pre- and post-settlement stages of the Programme by cooperating the supporting services to Government; - Inputs from the communities in rural areas where the settlement takes place; - The landowners as sellers of land (e.g. a Traditional Council); and - The emerging beneficiaries as the receivers of land. Mentorship is mostly the medium with which the support are coordinated. In this paper focus will be on three scenarios of different types of mentorship (or management support) namely: - The Taung Irrigation Scheme (TIS) where multiple new land beneficiaries were established by sharing irrigation pivots and receiving mentorship support from commodity organisations within a traditional land sharing system; - Projects whereby the mentor is a strategic partner (mostly a major agricultural 'cooperative' which is also providing inputs to the farmer and responsible for purchasing/marketing all commodities produced); and - An individual mentor who is a private person focussing mainly on farm management mentorship without direct gain other than a monthly stipend paid to the mentor by Government. Against this introduction the focus of the study is investigating the process for the sustainable implementation of Governments’ Land Redistribution in South African Agriculture. To achieve this, the research paper is presented under the themes of problem statement, objectives, methodology and limitations, outline of the research process, as well as proposing possible solutions.

Keywords: land reform, role-players, failures, mentorship, management models

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

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

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

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Authors: Francesca Fermi, Paola Astegiano, Angelo Martino, Stephanie Heitel, Michael Krail

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In order to achieve the targeted emission reductions for the decarbonisation of the European economy by 2050, fundamental contributions are required from both energy and transport sectors. The objective of this paper is to analyse the impacts of a largescale diffusion of e-vehicles, either battery-based or fuel cells, together with the implementation of transport policies aiming at decreasing the use of motorised private modes in order to achieve greenhouse gas emission reduction goals, in the context of a future high share of renewable energy. The analysis of the impacts and challenges of future scenarios on transport sector is performed with the ASTRA (ASsessment of TRAnsport Strategies) model. ASTRA is a strategic system-dynamic model at European scale (EU28 countries, Switzerland and Norway), consisting of different sub-modules related to specific aspects: the transport system (e.g. passenger trips, tonnes moved), the vehicle fleet (composition and evolution of technologies), the demographic system, the economic system, the environmental system (energy consumption, emissions). A key feature of ASTRA is that the modules are linked together: changes in one system are transmitted to other systems and can feed-back to the original source of variation. Thanks to its multidimensional structure, ASTRA is capable to simulate a wide range of impacts stemming from the application of transport policy measures: the model addresses direct impacts as well as second-level and third-level impacts. The simulation of the different scenarios is performed within the REFLEX project, where the ASTRA model is employed in combination with several energy models in a comprehensive Modelling System. From the transport sector perspective, some of the impacts are driven by the trend of electricity price estimated from the energy modelling system. Nevertheless, the major drivers to a low carbon transport sector are policies related to increased fuel efficiency of conventional drivetrain technologies, improvement of demand management (e.g. increase of public transport and car sharing services/usage) and diffusion of environmentally friendly vehicles (e.g. electric vehicles). The final modelling results of the REFLEX project will be available from October 2018. The analysis of the impacts and challenges of future scenarios is performed in terms of transport, environmental and social indicators. The diffusion of e-vehicles produces a consistent reduction of future greenhouse gas emissions, although the decarbonisation target can be achieved only with the contribution of complementary transport policies on demand management and supporting the deployment of low-emission alternative energy for non-road transport modes. The paper explores the implications through time of transport policy measures on mobility and environment, underlying to what extent they can contribute to a decarbonisation of the transport sector. Acknowledgements: The results refer to the REFLEX project which has received grants from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 691685.

Keywords: decarbonisation, greenhouse gas emissions, e-mobility, transport policies, energy

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

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Authors: Neha Adsul, Rohit Shah

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Background: The global history of nursing is exclusively a history of deep contradictions as it seeks to negotiate inclusion in an already gendered world. Although a powerful 'clinical gaze exists, nurses have toiled to re-negotiate and subvert the 'medical gaze' by practicing the 'therapeutic gaze' to tether back 'care into nursing practice.' This helps address the duality of the 'body' and 'mind' wherein the patient is not just limited to being an object of medical inquiry. Nevertheless, there has been a consistent effort to fit 'nursing' into being an art or an emerging science over the years. Especially with advances in hospital-based techno-centric medical practices, the boundaries between technology and nursing practices are becoming more blurred as the technical process becomes synonymous with nursing, eroding the essence of nursing care. Aim: This paper examines the history of nursing and offers insights into how gendered relations and the ideological belief of 'nursing as gendered work' have propagated to the subjugation of the nursing profession. It further aims to provide insights into the patriarchally imbibed techno-centrism that negates the gendered caregiving which lies at the crux of a nurse's work. Method: A literature search was carried out using Google Scholar, Web of Science and PubMed databases. Search words included: technology and nursing, medical technology and nursing, history of nursing, sociology and nursing and nursing care. The history of nursing is presented in a discussion that weaves together the historical events of the 'Birth of the Clinic' and the shift from 'bed-side medicine' to 'hospital-based medicine' that legitimizes exploitation of the bodies of patients to the 'medical gaze while the emergence of nursing as acquiescent to instrumental, technical, positivist and dominant views of medicine. The resultant power asymmetries, wherein in contemporary nursing, the constant struggle of nurses to juggle between being the physicians "operational right arm" to harboring that subjective understanding of the patients to refrain from de-humanizing nursing-care. Findings: The nursing profession suffers from being rendered invisible due to gendered relations having patrifocal societal roots. This perpetuates a notion rooted in the idea that emphasizes empiricism and has resulted in theoretical and epistemological fragmentation of the understanding of body and mind as separate entities. Nurses operate within this structure while constantly being at the brink of being pushed beyond the legitimate professional boundaries while being labeled as being 'unscientific' as the work does not always corroborate and align with the existing dominant positivist lines of inquiries. Conclusion: When understood in this broader context of how nursing as a practice has evolved over the years, it provides a particularly crucial testbed for understanding contemporary gender relations. Not because nurses like to live in a gendered work trap but because the gendered relations at work are written in a covert narcissistic patriarchal milieu that fails to recognize the value of intangible yet utmost necessary 'caring work in nursing. This research urges and calls for preserving and revering the humane aspect of nursing care alongside the emerging tech-savvy expectations from nursing work.

Keywords: nursing history, technocentric, power relations, scientific duality

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Authors: Alondra Balbuena Medina, Carlos Diaz Delgado, Aleida Yadira Vilchis Fránces

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In Mexico, each year news is disseminated about the ravages of floods, such as the total loss of housing, damage to the fields; the increase of the costs of the food, derived from the losses of the harvests, coupled with health problems such as skin infection, etc. In addition to social problems such as delinquency, damage in education institutions and the population in general. The flooding is a consequence of heavy rains, tropical storms and or hurricanes that generate excess water in drainage systems that exceed its capacity. In urban areas, heavy rains can be one of the main factors in causing flooding, in addition to excessive precipitation, dam breakage, and human activities, for example, excessive garbage in the strainers. In agricultural areas, these can hardly achieve large areas of cultivation. It should be mentioned that for both areas, one of the significant impacts of floods is that they can permanently affect the livelihoods of many families, cause damage, for example in their workplaces such as farmlands, commercial or industry areas and where services are provided. In recent years, Information and Communication Technologies (ICT) have had an accelerated development, being reflected in the growth and the exponential evolution of the innovation giving; as a result, the daily generation of new technologies, updates, and applications. Innovation in the development of Information Technology applications has impacted on all areas of human activity. They influence all the orders of life of individuals, reconfiguring the way of perceiving and analyzing the world such as, for instance, interrelating with people as individuals and as a society, in the economic, political, social, cultural, educational, environmental, etc. Therefore the present work describes the creation of a system of calculation of flood costs for housing areas, retail establishments and agricultural areas from the Mexican Republic, based on the use and application of geotechnical tools being able to be useful for the benefit of the sectors of public, education and private. To generate analysis of hydrometereologic affections and with the obtained results to realize the Geoinformatics tool was constructed from two different points of view: the geoinformatic (design and development of GIS software) and the methodology of flood damage validation in order to integrate a tool that provides the user the monetary estimate of the effects caused by the floods. With information from the period 2000-2014, the functionality of the application was corroborated. For the years 2000 to 2009 only the analysis of the agricultural and housing areas was carried out, incorporating for the commercial establishment's information of the period 2010 - 2014. The method proposed for the resolution of this research project is a fundamental contribution to society, in addition to the tool itself. Therefore, it can be summarized that the problems that are in the physical-geographical environment, conceiving them from the point of view of the spatial analysis, allow to offer different alternatives of solution and also to open up slopes towards academia and research.

Keywords: floods, technological innovation, monetary estimation, spatial analysis

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Authors: Charlotte Jeavons, Charitini Stavropoulous, Nicolas Drey

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Background: Over one-third of five-year-olds and almost half of all eight-year-olds in the UK have obvious caries experience that can be detected by visual screening techniques. School-based caries preventions programs to apply fluoride varnish to young children’s teeth operate in many areas in the UK. Their aim is to reduce dental caries in children. The Department of Health guidance (2009) on consent states information must be provided to parents to enable informed autonomous decision-making prior to any treatment involving their young children. Fluoride varnish schemes delivered in primary schools use letters for this purpose. Parents are expected to return these indicating their consent or refusal. A large proportion of parents do not respond. In the absence of positive consent, these children are excluded from the program. Non-response is more common in deprived areas creating inequality. The reason for this is unknown. The consent process used is underpinned by the ethical theory of deontology that is prevalent in clinical dentistry and widely accepted in bio-ethics. Objective: To investigate parents’ views, understanding and experience of the fluoride varnish program taking place in their child’s school, including their views about the practical consent arrangements. Method: Schools participating in the fluoride varnish scheme operating in Enfield, North London, were asked to take part. Parents with children in nursery, reception, or year one were invited to participate via semi-structured interviews and focus groups. Thematic analysis was conducted. Findings: 40 parents were recruited from eight schools. The global theme of ‘trust’ was identified as the strongest influence on parental responses. Six themes were identified; protecting children from harm is viewed by parents as their role, parents have the capability to decide but lack confidence, sharing responsibility for their child’s oral health with the State is welcomed by a parent, existing relationships within parents’ social networks strongly influences consent decisions, official dental information is not communicated effectively, sending a letter to parents’ and excluding them from meeting dental practitioners is ineffective. The information delivered via a letter was not strongly identified by parents as influencing their response. Conclusions: Personal contact with the person(s) providing information and requesting consent has a greater impact on parental consent responses than written information provided alone. This demonstrates that traditional bio-ethical ideas about rational decision-making where emotions are transcended and interference is not justified unless preventing harm to an unaware person are outdated. Parental decision-making is relational and the consent process should be adapted to reflect this. The current system that has a deontology view of decision making at its core impoverishes parental autonomy and may, ultimately, increase dental inequalities as a result.

Keywords: consent, decision, ethics, fluoride, parents

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Authors: Mette Dalgaard Nielsen

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The paper serves the purpose of providing an eco-systemic typology of fashion resale business models in Denmark while pointing to possibilities to learn from its wisdom during a time when a fundamental break with the dominant linear fashion paradigm has become inevitable. As we transgress planetary boundaries and can no longer continue the unsustainable path of over-exploiting the Earth’s resources, the global fashion industry faces a tremendous need for change. One of the preferred answers to the fashion industry’s sustainability crises lies in the circular economy, which aims to maximize the utilization of resources by keeping garments in use for longer. Thus, in the context of fashion, resale business models that allow pre-owned garments to change hands with the purpose of being reused in continuous cycles are considered to be among the most efficient forms of circularity. Methodologies: The paper is based on empirical data from an ongoing project and a series of qualitative pilot studies that have been conducted on the Danish resale market over a 2-year time period from Fall 2021 to Fall 2023. The methodological framework is comprised of (n) ethnography and fieldwork in selected resale environments, as well as semi-structured interviews and a workshop with eight business partners from the Danish fashion and textiles industry. By focusing on the real-world circulation of pre-owned garments, which is enabled by the identified resale business models, the research lets go of simplistic hypotheses to the benefit of dynamic, vibrant and non-linear processes. As such, the paper contributes to the emerging research field of circular economy and fashion, which finds itself in a critical need to move from non-verified concepts and theories to empirical evidence. Findings: Based on the empirical data and anchored in the business partners, the paper analyses and presents five distinct resale business models with different product, service and design characteristics. These are 1) branded resale, 2) trade-in resale, 3) peer-2-peer resale, 4) resale boutiques and consignment shops and 5) resale shelf/square meter stores and flea markets. Together, the five business models represent a plurality of resale-promoting business model design elements that have been found to contribute to the circulation of pre-owned garments in various ways for different garments, users and businesses in Denmark. Hence, the provided typology points to the necessity of prioritizing several rather than single resale business model designs, services and initiatives for the resale market to help reconfigure the linear fashion model and create a circular-ish future. Conclusions: The article represents a twofold research ambition by 1) presenting an original, up-to-date eco-systemic typology of resale business models in Denmark and 2) using the typology and its eco-systemic traits as a tool to understand different business model design elements and possibilities to help fashion grow out of its linear growth model. By basing the typology on eco-systemic mechanisms and actual exemplars of resale business models, it becomes possible to envision the contours of a genuine alternative to business as usual that ultimately helps bend the linear fashion model towards circularity.

Keywords: circular business models, circular economy, fashion, resale, strategic design, sustainability

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Authors: Alexis D'Agostino, Celeste Sununtunasuk, Jack Fiedler

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Background: Iron-folic acid (IFA) supplementation during antenatal care (ANC) has existed in many countries for decades. Despite this, low national coverage persists and women do not often consume appropriate amounts during pregnancy. USAID’s SPRING Project investigated pregnant women’s access to, and consumption of, IFA tablets through ANC. Cross-country analysis provided a global picture of the state of IFA-supplementation, while country-specific results noted key contextual issues, including geography, wealth, and ANC attendance. The analysis can help countries prioritize strategies for systematic performance improvements within one of the most common micronutrient supplementation programs aimed at reducing maternal anemia. Methodology: Using falter point analysis on Demographic and Health Survey (DHS) data collected from 162,958 women across 22 countries, SPRING identified four sequential falter points (ANC attendance, IFA receipt or purchase, IFA consumption, and number of tablets taken) where pregnant women fell out of the IFA distribution structure. SPRING analyzed data on IFA intake from DHS surveys with women of reproductive age. SPRING disaggregated these data by ANC participation during the most recent pregnancy, residency, and women’s socio-economic status. Results: Average sufficient IFA tablet use across all countries was only eight percent. Even in the best performing countries, only about one-third of pregnant women consumed 180 or more IFA tablets during their most recent pregnancy. ANC attendance was an important falter point for a quarter of women across all countries (with highest falter rates in Democratic Republic of the Congo, Nigeria, and Niger). Further analysis reveals patterns, with some countries having high ANC coverage but low IFA provision during ANC (DRC and Haiti), others having high ANC coverage and IFA provision but few women taking any tablets (Nigeria and Liberia), and countries that perform well in ANC, supplies, and initial consumption but where very few women consume the recommended 180 tablets (Malawi and Cambodia). Country-level analysis identifies further patterns of supplementation. In Indonesia, for example, only 62% of women in the poorest quintile took even one IFA tablet, while 86% of the wealthiest women did. This association between socioeconomic status and IFA intake held across nearly all countries where these data are available and was also visible in rural/urban comparisons. Analysis of ANC attendance data also suggests that higher numbers of ANC visits are associated with higher tablet intake. Conclusions: While it is difficult to disentangle which specific aspects of supply or demand cause the low rates of consumption, this tool allows policy-makers to identify major bottlenecks to scaling-up IFA supplementation during ANC. In turn, each falter point provides possible explanations of program performance and helps strategically identify areas for improved IFA supplementation. For example, improving the delivery of IFA supplementation in Ethiopia relies on increasing access to ANC, but also on identifying and addressing program gaps in IFA supply management and health workers’ practices in order to provide quality ANC services. While every country requires a customized approach to improving IFA supplementation, the multi-country analysis conducted by SPRING is a helpful first step in identifying country bottlenecks and prioritizing interventions.

Keywords: iron and folic acid, supplementation, antenatal care, micronutrient

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Authors: Tolga Levent

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Throughout the past few decades, forced immigration has been a significant problem for many developing countries. Turkey is one of those countries, which has experienced lots of forced immigration waves in the Republican era. However, the ongoing forced immigration wave of Syrians started with Syrian Civil War in 2011, is strikingly influential due to its intensity. In six years, approximately 3,4 million Syrians have entered to Turkey and presented high-level spatial concentrations in certain cities proximate to the Syrian border. These concentrations make Syrians and their problems relatively visible, especially in those cities. The problems of Syrians in Turkish cities could be associated with all dimensions of daily lives. Within economical dimension, high rates of Syrian unemployment push them to informal jobs offering very low wages. The financial aids they continuously demand from public authorities trigger anti-Syrian behaviors of local communities. Moreover, their relatively limited social adaptation capacities increase integration problems within social dimension day by day. Even, there are problems related to public health dimension such as the reappearance of certain child's illnesses due to the insufficiency of vaccination of Syrian children. These problems are significant but relatively easy to be prevented by using different types of management strategies and structural policies. However, there are other types of problems -urban problems- emerging with socio-spatial impacts of Syrians on Turkish cities in a very short period of time. There are relatively limited amount of studies about these impacts since they are difficult to be comprehended. The aim of the study, in this respect, is to understand these rapidly-emerging impacts and urban problems resulted from this massive immigration influx and to discuss new qualities of urban planning facing them. In the first part, there is a brief historical consideration of forced immigration waves in Turkey. These waves are important to make comparison with the ongoing immigration wave and to understand its significance. The second part is about quantitative and qualitative analyses of the spatial existence of Syrian immigrants in the city of Mersin, as an example of cities where Syrians are highly concentrated. By using official data from public authorities, quantitative statistical analyses are made to detect spatial concentrations of Syrians at neighborhood level. As methods of qualitative research, observations and in-depth interviews are used to define socio-spatial impacts of Syrians. The main results show that there emerges 'cities in cities' though sharp socio-spatial segregations which change density surfaces; produce unforeseen land-use patterns; result in inadequacies of public services and create degradations/deteriorations of urban environments occupied by Syrians. All these problems are significant; however, Turkish planning system does not have a capacity to cope with them. In the final part, there is a discussion about new qualities of urban planning facing these impacts and urban problems. The main point of discussion is the possibility of resilient urban planning under the conditions of uncertainty and unpredictability fostered by immigration crisis. Such a resilient planning approach might provide an option for countries aiming to cope with negative socio-spatial impacts of massive immigration influxes.

Keywords: cities, forced immigration, Syrians, urban planning

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Authors: B. Sudhakara Reddy

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This study provides a snapshot of the sustainability of selected Indian cities by employing 70 indicators in four dimensions to develop an overall city sustainability index. In recent years, the concept of ‘urban sustainability’ has become prominent due to its complexity. Urban areas propel growth and at the same time poses a lot of ecological, social and infrastructural problems and risks. In case of developing countries, the high population density of and the continuous in-migration run the highest risk in natural and man-made disasters. These issues combined with the inability of policy makers in providing basic services makes the cities unsustainable. To assess whether any given policy is moving towards or against urban sustainability it is necessary to consider the relationships among its various dimensions. Hence, in recent years, while preparing the sustainability index, an integral approach involving indicators of different dimensions such as ‘economic’, ‘environmental’ and 'social' is being used. It is also important for urban planners, social analysts and other related institutions to identify and understand the relationships in this complex system. The objective of the paper is to develop a city performance index (CPI) to measure and evaluate the urban regions in terms of sustainable performances. The objectives include: i) Objective assessment of a city’s performance, ii) setting achievable goals iii) prioritise relevant indicators for improvement, iv) learning from leaders, iv) assessment of the effectiveness of programmes that results in achieving high indicator values, v) Strengthening of stakeholder participation. Using the benchmark approach, a conceptual framework is developed for evaluating 25 Indian cities. We develop City Sustainability index (CSI) in order to rank cities according to their level of sustainability. The CSI is composed of four dimensions: Economic, Environment, Social, and Institutional. Each dimension is further composed of multiple indicators: (1) Economic that considers growth, access to electricity, and telephone availability; (2) environmental that includes waste water treatment, carbon emissions, (3) social that includes, equity, infant mortality, and 4) institutional that includes, voting share of population, urban regeneration policies. The CSI, consisting of four dimensions disaggregate into 12 categories and ultimately into 70 indicators. The data are obtained from public and non-governmental organizations, and also from city officials and experts. By ranking a sample of diverse cities on a set of specific dimensions the study can serve as a baseline of current conditions and a marker for referencing future results. The benchmarks and indices presented in the study provide a unique resource for the government and the city authorities to learn about the positive and negative attributes of a city and prepare plans for a sustainable urban development. As a result of our conceptual framework, the set of criteria we suggest is somewhat different to any already in the literature. The scope of our analysis is intended to be broad. Although illustrated with specific examples, it should be apparent that the principles identified are relevant to any monitoring that is used to inform decisions involving decision variables. These indicators are policy-relevant and, hence they are useful tool for decision-makers and researchers.

Keywords: benchmark, city, indicator, performance, sustainability

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Authors: Carolina Busco, Daniela Osses

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The development of digital literacy has become a fundamental element that allows for citizen inclusion, access to quality jobs, and a labor market capable of responding to the digital economy. There are no methodological instruments available in Chile to measure the workforce’s digital literacy and improve national policies on this matter. Thus, the objective of this research is to develop a survey to measure digital literacy in a sample of 200 Chilean workers. Dimensions considered in the instrument are sociodemographics, access to infrastructure, digital education, digital skills, and the ability to use e-government services. To achieve the research objective of developing a digital literacy model of indicators and a research instrument for this purpose, along with an exploratory analysis of data using factor analysis, we used an empirical, quantitative-qualitative, exploratory, non-probabilistic, and cross-sectional research design. The research instrument is a survey created to measure variables that make up the conceptual map prepared from the bibliographic review. Before applying the survey, a pilot test was implemented, resulting in several adjustments to the phrasing of some items. A validation test was also applied using six experts, including their observations on the final instrument. The survey contained 49 items that were further divided into three sets of questions: sociodemographic data; a Likert scale of four values ranked according to the level of agreement; iii) multiple choice questions complementing the dimensions. Data collection occurred between January and March 2022. For the factor analysis, we used the answers to 12 items with the Likert scale. KMO showed a value of 0.626, indicating a medium level of correlation, whereas Bartlett’s test yielded a significance value of less than 0.05 and a Cronbach’s Alpha of 0.618. Taking all factor selection criteria into account, we decided to include and analyze four factors that together explain 53.48% of the accumulated variance. We identified the following factors: i) access to infrastructure and opportunities to develop digital skills at the workplace or educational establishment (15.57%), ii) ability to solve everyday problems using digital tools (14.89%), iii) online tools used to stay connected with others (11.94%), and iv) residential Internet access and speed (11%). Quantitative results were discussed within six focus groups using heterogenic selection criteria related to the most relevant variables identified in the statistical analysis: upper-class school students; middle-class university students; Ph.D. professors; low-income working women, elderly individuals, and a group of rural workers. The digital divide and its social and economic correlations are evident in the results of this research. In Chile, the items that explain the acquisition of digital tools focus on access to infrastructure, which ultimately puts the first filter on the development of digital skills. Therefore, as expressed in the literature review, the advance of these skills is radically different when sociodemographic variables are considered. This increases socioeconomic distances and exclusion criteria, putting those who do not have these skills at a disadvantage and forcing them to seek the assistance of others.

Keywords: digital literacy, digital society, workforce digitalization, digital skills

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Authors: Wen Liu, Errol Haarhoff, Lee Beattie

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In 2010, New Zealand’s central government re-organise the local governments arrangements in Auckland, New Zealand by amalgamating its previous regional council and seven supporting local government units into a single unitary council, the Auckland Council. The Auckland Council is charged with providing local government services to approximately 1.5 million people (a third of New Zealand’s total population). This includes addressing Auckland’s strategic urban growth management and setting its urban planning policy directions for the next 40 years. This is expressed in the first ever spatial plan in the region – the Auckland Plan (2012). The Auckland plan supports implementing a compact city model by concentrating the larger part of future urban growth and development in, and around, existing and proposed transit centres, with the intention of Auckland to become globally competitive city and achieving ‘the most liveable city in the world’. Turning that vision into reality is operatized through the statutory land use plan, the Auckland Unitary Plan. The Unitary plan replaced the previous regional and local statutory plans when it became operative in 2016, becoming the ‘rule book’ on how to manage and develop the natural and built environment, using land use zones and zone standards. Common to the broad range of literature on urban growth management, one significant issue stands out about intensification. The ‘gap’ between strategic planning and what has been achieved is evident in the argument for the ‘compact’ urban form. Although the compact city model may have a wide range of merits, the extent to which these are actualized largely rely on how intensification actually is delivered. The transformation of the rhetoric of the residential intensification model into reality is of profound influence, yet has enjoyed limited empirical analysis. In Auckland, the establishment of the Auckland Plan set up the strategies to deliver intensification into diversified arenas. Nonetheless, planning policy itself does not necessarily achieve the envisaged objectives, delivering the planning system and high capacity to enhance and sustain plan implementation is another demanding agenda. Though the Auckland Plan provides a wide ranging strategic context, its actual delivery is beholden on the Unitary Plan. However, questions have been asked if the Unitary Plan has the necessary statutory tools to deliver the Auckland Plan’s policy outcomes. In Auckland, there is likely to be continuing tension between the strategies for intensification and their envisaged objectives, and made it doubtful whether the main principles of the intensification strategies could be realized. This raises questions over whether the Auckland Plan’s policy goals can be achieved in practice, including delivering ‘quality compact city’ and residential intensification. Taking Auckland as an example of traditionally sprawl cities, this article intends to investigate the efficacy plan making and implementation directed towards higher density development. This article explores the process of plan development, plan making and implementation frameworks of the first ever spatial plan in Auckland, so as to explicate the objectives and processes involved, and consider whether this will facilitate decision making processes to realize the anticipated intensive urban development.

Keywords: urban intensification, sustainable development, plan making, governance and implementation

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Christina Largent, Tazley Hobbs

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Objective: A literature review was performed to examine the existing research on COVID-19 lockdown as it relates to ADHD child/adolescent individuals, media use, and impact on educational performance/learning. It was surmised that with the COVID-19 shut-down and transition to remote learning, a less structured learning environment, increased screen time, in addition to potential difficulty accessing school resources would impair ADHD individuals’ performance and learning. A resulting increase in the number of youths diagnosed and treated for ADHD would be expected. As of yet, there has been little to no published data on the incidence of ADHD as it relates to COVID-19 outside of reports from several nonprofit agencies such as CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder ), who reported an increased number of calls to their helpline, The New York based Child Mind Institute, who reported an increased number of appointments to discuss medications, and research released from Athenahealth showing an increase in the number of patients receiving new diagnosis of ADHD and new prescriptions for ADHD medications. Methods: A literature search for articles published between 2020 and 2021 from Pubmed, Google Scholar, PsychInfo, was performed. Search phrases and keywords included “covid, adhd, child, impact, remote learning, media, screen”. Results: Studies primarily utilized parental reports, with very few from the perspective of the ADHD individuals themselves. Most findings thus far show that with the COVID-19 quarantine and transition to online learning, ADHD individuals’ experienced decreased ability to keep focused or adhere to the daily routine, as well as increased inattention-related problems, such as careless mistakes or lack of completion in homework, which in turn translated into overall more difficulty with remote learning. To add further injury, one study showed (just on evaluation of two different sites within the US) that school based services for these individuals decreased with the shift to online-learning. Increased screen time, television, social media, and gaming were noted amongst ADHD individuals. One study further differentiated the degree of digital media, identifying individuals with “problematic “ or “non-problematic” use. ADHD children with problematic digital media use suffered from more severe core symptoms of ADHD, negative emotions, executive function deficits, damage to family environment, pressure from life events, and a lower motivation to learn. Conclusions and Future Considerations: Studies found not only was online learning difficult for ADHD individuals but it, in addition to greater use of digital media, was associated with worsening ADHD symptoms impairing schoolwork, in addition to secondary findings of worsening mood and behavior. Currently, data on the number of new ADHD cases, in addition to data on the prescription and usage of stimulants during COVID-19, has not been well documented or studied; this would be well-warranted out of concern for over diagnosing or over-prescribing our youth. It would also be well-worth studying how reversible or long-lasting these negative impacts may be.

Keywords: COVID-19, remote learning, media use, ADHD, child, adolescent

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Authors: B. Godefroy, D. Beladjine, K. Beddiar

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In France, construction BIM actors commonly evoke the BIM gains for exploitation by integrating of the life cycle of a building. The standardization of level 7 of development would achieve this stage of the digital model. The householders include local public authorities, social landlords, public institutions (health and education), enterprises, facilities management companies. They have a dual role: owner and manager of their housing complex. In a context of financial constraint, the BIM of exploitation aims to control costs, make long-term investment choices, renew the portfolio and enable environmental standards to be met. It assumes a knowledge of the existing buildings, marked by its size and complexity. The information sought must be synthetic and structured, it concerns, in general, a real estate complex. We conducted a study with professionals about their concerns and ways to use it to see how householders could benefit from this development. To obtain results, we had in mind the recurring interrogation of the project management, on the needs of the operators, we tested the following stages: 1) Inculcate a minimal culture of BIM with multidisciplinary teams of the operator then by business, 2) Learn by BIM tools, the adaptation of their trade in operations, 3) Understand the place and creation of a graphic and technical database management system, determine the components of its library so their needs, 4) Identify the cross-functional interventions of its managers by business (operations, technical, information system, purchasing and legal aspects), 5) Set an internal protocol and define the BIM impact in their digital strategy. In addition, continuity of management by the integration of construction models in the operation phase raises the question of interoperability in the control of the production of IFC files in the operator’s proprietary format and the export and import processes, a solution rivaled by the traditional method of vectorization of paper plans. Companies that digitize housing complex and those in FM produce a file IFC, directly, according to their needs without recourse to the model of construction, they produce models business for the exploitation. They standardize components, equipment that are useful for coding. We observed the consequences resulting from the use of the BIM in the property industry and, made the following observations: a) The value of data prevail over the graphics, 3D is little used b) The owner must, through his organization, promote the feedback of technical management information during the design phase c) The operator's reflection on outsourcing concerns the acquisition of its information system and these services, observing the risks and costs related to their internal or external developments. This study allows us to highlight: i) The need for an internal organization of operators prior to a response to the construction management ii) The evolution towards automated methods for creating models dedicated to the exploitation, a specialization would be required iii) A review of the communication of the project management, management continuity not articulating around his building model, it must take into account the environment of the operator and reflect on its scope of action.

Keywords: information system, interoperability, models for exploitation, property industry

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Javier E. García-Gallo, Nelson J. Fonseca-Ruiz, John F. Duitama-Munoz

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Sepsis is a syndrome that occurs with physiological and biochemical abnormalities induced by severe infection and carries a high mortality and morbidity, therefore the severity of its condition must be interpreted quickly. After patient admission in an intensive care unit (ICU), it is necessary to synthesize the large volume of information that is collected from patients in a value that represents the severity of their condition. Traditional severity of illness scores seeks to be applicable to all patient populations, and usually assess in-hospital mortality. However, the use of machine learning techniques and the data of a population that shares a common characteristic could lead to the development of customized mortality prediction scores with better performance. This study presents the development of a score for the one-year mortality prediction of the patients that are admitted to an ICU with a sepsis diagnosis. 5650 ICU admissions extracted from the MIMICIII database were evaluated, divided into two groups: 70% to develop the score and 30% to validate it. Comorbidities, demographics and clinical information of the first 24 hours after the ICU admission were used to develop a mortality prediction score. LASSO (least absolute shrinkage and selection operator) and SGB (Stochastic Gradient Boosting) variable importance methodologies were used to select the set of variables that make up the developed score; each of this variables was dichotomized and a cut-off point that divides the population into two groups with different mean mortalities was found; if the patient is in the group that presents a higher mortality a one is assigned to the particular variable, otherwise a zero is assigned. These binary variables are used in a logistic regression (LR) model, and its coefficients were rounded to the nearest integer. The resulting integers are the point values that make up the score when multiplied with each binary variables and summed. The one-year mortality probability was estimated using the score as the only variable in a LR model. Predictive power of the score, was evaluated using the 1695 admissions of the validation subset obtaining an area under the receiver operating characteristic curve of 0.7528, which outperforms the results obtained with Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS) and Simplified Acute Physiology Score II (SAPSII) scores on the same validation subset. Observed and predicted mortality rates within estimated probabilities deciles were compared graphically and found to be similar, indicating that the risk estimate obtained with the score is close to the observed mortality, it is also observed that the number of events (deaths) is indeed increasing as the outcome go from the decile with the lowest probabilities to the decile with the highest probabilities. Sepsis is a syndrome that carries a high mortality, 43.3% for the patients included in this study; therefore, tools that help clinicians to quickly and accurately predict a worse prognosis are needed. This work demonstrates the importance of customization of mortality prediction scores since the developed score provides better performance than traditional scoring systems.

Keywords: intensive care, logistic regression model, mortality prediction, sepsis, severity of illness, stochastic gradient boosting

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Authors: Binbin Chen, Dennis Y. C. Leung

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Aluminium (Al) -air cell holds a high volumetric capacity density of 8.05 Ah cm-3, benefit from the trivalence of Al ions. Additional benefits of Al-air cell are low price and environmental friendliness. Furthermore, the Al energy conversion process is characterized of 100% recyclability in theory. Along with a large base of raw material reserve, Al attracts considerable attentions as a promising material to be integrated within the global energy system. However, despite the early successful applications in military services, several problems exist that prevent the Al-air cells from widely civilian use. The most serious issue is the parasitic corrosion of Al when contacts with electrolyte. To overcome this problem, super-pure Al alloyed with various traces of metal elements are used to increase the corrosion resistance. Nevertheless, high-purity Al alloys are costly and require high energy consumption during production process. An alternative approach is to add inexpensive inhibitors directly into the electrolyte. However, such additives would increase the internal ohmic resistance and hamper the cell performance. So far these methods have not provided satisfactory solutions for the problem within Al-air cells. For the operation of alkaline Al-air cell, there are still other minor problems. One of them is the formation of aluminium hydroxide in the electrolyte. This process decreases ionic conductivity of electrolyte. Another one is the carbonation process within the gas diffusion layer of cathode, blocking the porosity of gas diffusion. Both these would hinder the performance of cells. The present work optimizes the above problems by building an Al-air cell operation system, consisting of four components. A top electrolyte tank containing fresh electrolyte is located at a high level, so that it can drive the electrolyte flow by gravity force. A mechanical rechargeable Al-air cell is fabricated with low-cost materials including low grade Al, carbon paper, and PMMA plates. An electrolyte waste tank with elaborate channel is designed to separate the hydrogen generated from the corrosion, which would be collected by gas collection device. In the first section of the research work, we investigated the performance of the mechanical rechargeable Al-air cell with a constant flow rate of electrolyte, to ensure the repeatability experiments. Then the whole system was assembled together and the feasibility of operating was demonstrated. During experiment, pure hydrogen is collected by collection device, which holds potential for various applications. By collecting this by-product, high utilization efficiency of aluminum is achieved. Considering both electricity and hydrogen generated, an overall utilization efficiency of around 90 % or even higher under different working voltages are achieved. Fluidic electrolyte could remove aluminum hydroxide precipitate and solve the electrolyte deterioration problem. This operation system provides a low-cost strategy for harvesting energy from the abundant secondary Al. The system could also be applied into other metal-air cells and is suitable for emergency power supply, power plant and other applications. The low cost feature implies great potential for commercialization. Further optimization, such as scaling up and optimization of fabrication, will help to refine the technology into practical market offerings.

Keywords: aluminium-air cell, high efficiency, hydrogen, mechanical recharge

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Ronald Orth, Johanna Haunschild, Sara Tsog

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The bioeconomy is an inter- and cross-disciplinary field covering a large number and wide scope of existing and emerging technologies. It has a great potential to contribute to the transformation process of industry landscape and ultimately drive the economy towards sustainability. However, bioeconomy per se is not necessarily sustainable and technology should be seen as an enabler rather than panacea to all our ecological, social and economic issues. Therefore, to draw and maximize benefits from bioeconomy in terms of sustainability, we propose that innovative activities should encompass not only novel technologies and bio-based new materials but also multifocal innovations. For multifocal innovation endeavors, innovation management plays a substantial role, as any innovation emerges in a complex iterative process where communication and knowledge exchange among relevant stake holders has a pivotal role. The knowledge generation and innovation are although at the core of transition towards a more sustainable bio-based economy, to date, there is a significant lack of concepts and models that approach bioeconomy from the innovation management approach. The aim of this paper is therefore two-fold. First, it inspects the role of transformative approach in the adaptation of bioeconomy that contributes to the environmental, ecological, social and economic sustainability. Second, it elaborates the importance of technology and innovation management as a tool for smooth, prompt and effective transition of firms to the bioeconomy. We conduct a qualitative literature study on the sustainability challenges that bioeconomy entails thus far using Science Citation Index and based on grey literature, as major economies e.g. EU, USA, China and Brazil have pledged to adopt bioeconomy and have released extensive publications on the topic. We will draw an example on the forest based business sector that is transforming towards the new green economy more rapidly as expected, although this sector has a long-established conventional business culture with consolidated and fully fledged industry. Based on our analysis we found that a successful transition to sustainable bioeconomy is conditioned on heterogenous and contested factors in terms of stakeholders , activities and modes of innovation. In addition, multifocal innovations occur when actors from interdisciplinary fields engage in intensive and continuous interaction where the focus of innovation is allocated to a field of mutually evolving socio-technical practices that correspond to the aims of the novel paradigm of transformative innovation policy. By adopting an integrated and systems approach as well as tapping into various innovation networks and joining global innovation clusters, firms have better chance of creating an entire new chain of value added products and services. This requires professionals that have certain capabilities and skills such as: foresight for future markets, ability to deal with complex issues, ability to guide responsible R&D, ability of strategic decision making, manage in-depth innovation systems analysis including value chain analysis. Policy makers, on the other hand, need to acknowledge the essential role of firms in the transformative innovation policy paradigm.

Keywords: bioeconomy, innovation and technology management, multifocal innovation, sustainability, transformative innovation policy

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Authors: Ayse Collins

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The Agenda 2030 puts Higher Education Institutions (HEIs) in the situation where they should emphasize ways to promote sustainability accordingly. However, it is still unclear: a) how sustainability is understood, and b) which actions have been taken in both discourse and practice by HEIs regarding the three pillars of sustainability, society, environment, and economy. There are models of sustainable universities developed by different authors from different countries; For Example, The Global Reporting Initiative (GRI) methodology which offers a variety of indicators to diagnose performance. However, these models have never been developed for universities in particular. Any model, in this sense, cannot be completed adequately without defining the appropriate tools to measure, analyze and control the performance of initiatives. There is a need to conduct researches in different universities from different countries to understand where we stand in terms of sustainable higher education. Therefore, this study aims at exploring the actions taken by a university in Ankara, Turkey, since Agenda 2030 should consider localizing its objectives and targets according to a certain geography. This university just announced 2021-2022 as “Sustainability Year.” Therefore, this research is a multi-methodology longitudinal study and uses the theoretical framework of the organization and transition management (TM). It is designed to examine the activities as being strategic, tactical, operational, and reflexive in nature and covers the six main aspects: academic community, administrative staff, operations and services, teaching, research, and extension. The preliminary research will answer the role of the top university governance, perception of the stakeholders (students, instructors, administrative and support staff) regarding sustainability, and the level of achievement at the mid-evaluation and final, end of year evaluation. TM Theory is a multi-scale, multi-actor, process-oriented approach with the analytical framework to explore and promote change in social systems. Therefore, the stages and respective methodology for collecting data in this research is: Pre-development Stage: a) semi-structured interviews with university governance, c) open-ended survey with faculty, students, and administrative staff d) Semi-structured interviews with support staff, and e) analysis of current secondary data for sustainability. Take-off Stage: a) semi-structured interviews with university governance, faculty, students, administrative and support staff, b) analysis of secondary data. Breakthrough stabilization a) survey with all stakeholders at the university, b) secondary data analysis by using selected indicators for the first sustainability report for universities The findings from the predevelopment stage highlight how stakeholders, coming from different faculties, different disciplines with different identities and characteristics, face the sustainability challenge differently. Though similar sustainable development goals ((social, environmental, and economic) are set in the institution, there are differences across disciplines and among different stakeholders, which need to be considered to reach the optimum goal. It is believed that the results will help changes in HEIs organizational culture to embed sustainability values in their strategic planning, academic and managerial work by putting enough time and resources to be successful in coping with sustainability.

Keywords: higher education, sustainability, sustainability auditing, transition management

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Authors: Vinodhini Elangovan, Jen Heng Pek

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Background: An ectopic pregnancy is defined as any pregnancy implanted outside of the endometrial cavity. Cornual pregnancy, a rare variety of ectopic pregnancies, is seen in about 2-4% of ectopic pregnancies. It develops in the interstitial portion of the fallopian tube and invades through the uterine wall. This case describes a third-trimester cornual pregnancy that resulted in a uterine rupture. Case: A 38-year old Chinese lady was brought to the Emergency Department (ED) as a standby case for hypotension. She was 30+6 weeks pregnant (Gravida 3, Parous 1). Her past obstetric history included a live birth delivered via lower segment Caesarean section due to non-reassuring fetal status in 2002 and a miscarriage in 2012. She developed generalized abdominal pain. There was no per vaginal bleeding or leaking liquor. There was also no fever, nausea, vomiting, constipation, diarrhea, or urinary symptoms. On arrival in the ED, she was pale, diaphoretic, and lethargic. She had generalized tenderness with guarding and rebound over her abdomen. Point of care ultrasound was performed and showed a large amount of intra-abdominal free fluid, and the fetal heart rate was 170 beats per minute. The point of care hemoglobin was 7.1 g/dL, and lactate was 6.8 mmol/L. The patient’s blood pressure dropped precipitously to 50/36 mmHg, and her heart rate went up to 141 beats per minute. The clinical impression was profound shock secondary to uterine rupture. Intra-operatively, there was extensive haemoperitoneum, and the fetus was seen in the abdominal cavity. The fetus was delivered immediately and handed to the neonatal team. On exploration of the uterus, the point of rupture was at the left cornual region where the placenta was attached to. Discussion: Cornual pregnancies are difficult to diagnose pre-operatively with low ultrasonographic sensitivity and hence are commonly confused with normal intrauterine pregnancies. They pose a higher risk of rupture and hemorrhage compared to other types of ectopic pregnancies. In very rare circumstances, interstitial pregnancies can result in a viable fetus. Uterine rupture resulting in hemorrhagic shock is a true obstetric emergency that can result in significant morbidity and mortality for the patient and the fetus, and early diagnosis in the emergency department is crucial. The patient in this case presented with known risk factors of multiparity, advanced maternal age, and previous lower segment cesarean section, which increased the suspicion of uterine rupture. Ultrasound assessment may be beneficial to any patient who presents with symptoms and a history of uterine surgery to assess the possibility of uterine dehiscence or rupture. Management of a patient suspected of uterine rupture should be systematic in the emergency department and follow an ABC approach. Conclusion: This case demonstrates the importance for an emergency physician to maintain the suspicion for ectopic pregnancy even at advanced gestational ages. It also highlights how even though all emergency physicians may not be qualified to do a detailed pelvic ultrasound, it is essential for them to be competent with a point of care ultrasound to make a prompt diagnosis of conditions such as uterine rupture.

Keywords: cornual ectopic , ectopic pregnancy, emergency medicine, obstetric emergencies

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Authors: Leigha C. Crout

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This paper will investigate the categorical disregard of the People’s Republic of China (PRC) in establishing and maintaining a baseline standard of civil guarantees for economic migrant women and their dependents. In light of the relative forward strides in terms of policy facilitating the ascension of female workers in China, this oft-invisible subgroup of women remains neglected from the modern-day “iron rice bowl” of the self-identified communist state. This study is being undertaken to rectify the absence of data on this subject and provide a baseline for future studies on the matter, as the human rights of migrants has become an established facet of transnational dialogue and debate. The basic methodology of this research will consist of the evaluation of China’s compliance with its own national guidelines, and the eight international human rights law treaties it has ratified. Data will be extracted and cross-checked from a number of relevant sources to monitor the extent of compliance, including but by no means limited to the United Nations Human Rights Council (UNHRC) Universal Periodic Review (UPR) reports and responses, submissions and responses of international human rights treaty bodies, local and international nongovernmental organizations (NGOs) and their annual reports, and articles and commentaries authored by specialists on the modern state and implementation of Chinese law. Together, these data will illuminate the vast network of compliance that has forced many migrant women to work within situations of extreme economic precarity. The structure will proceed as follows: first, an outline of the current status of migrant workers and the enforcement of stipulated protections will be provided; next, the analysis of the oft-debated regulations directing and the outline of mandatory services guaranteed to external and internal migrants; and finally, a conclusion incorporating various recommendations to improve transparency and gradually decrease the amount of migrant work turned forced labor that typifies the economic migrant experience, especially in the case of women. The internal and international migrant workers in China are bound by different and uncomplimentary systems. The first, which governs Chinese citizens moving to different regions or provinces to find more sustainable employment (internal migrants), is called the hukou (or huji) residency system. This law enforces strict regulation of the movement of peoples, while ensuring that residents of urban areas receive preferential benefits to those received by their so-called “agricultural” resident counterparts. Given the overwhelming presence of the Communist Party of China throughout the vast state, the management of internal migrants and the disregard for foreign domestic workers is, at minimum, a surprising oversight. This paper endeavors to provide a much-needed foundation for future commentary and discussion on the treatment of female migrant workers and their families in the People’s Republic of China.

Keywords: female migrant worker’s rights, the People’s Republic of China, forced labor, Hukou residency system

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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