Search results for: physical growth of infants

Authors: Kirk Wickersham

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Introduction: Sprawl has been built for the auto. This project anticipates the adoption of autonomous vehicle technology to both enable and require a new urban form – a modern version of the organic form humans have developed over the millennia. It proposes a radically new land use decision-making system to stop further sprawl and channel growth into these new communities. Methodology: For the past 80 years we have built sprawl and strip commercial development – intense commercial and multifamily on the periphery, low-density housing in the center, repeated indefinitely across the landscape. Sprawl is designed to accommodate the auto, and we need an auto to live there. That will change. Within a decade, autonomous vehicles (AVs) and especially robotaxis will replace human-driven vehicles (HDVs). These new vehicles will require a new transportation network that will both enable and require a new urban form. It will resemble the organic urban form developed over millennia – high-intensity uses in the center, surrounded by neighborhoods, with a defined outer boundary – a city limit. The project dubs this new community a HOME Town Holistic, Organic, Market-driven, and Ergonomic. It will offer a better quality of life at a lower public and private cost. (While designing a transportation system primarily for alternative vehicles is not a requirement for creating a holistic, organic community, but it is the main reason for the reduced cost of housing, transportation, and public services). Sprawl is created by our existing land use decision-making system – local governments approving one incremental project at a time. To create these new communities, we will need a radically different system. This means regional planning, eliminating development-by-right zoning and incremental development approvals, new standards for roadways and parking, selection of a lead developer, designating and master planning a new community site, channeling development into the new community, and providing equity for the landowners who have been left out of the process. This new process is based on and inspired by state regulation of oilfield development, called “unitization and pooling.” It is designed to fit within standard state land use enabling legislation, although the states vary on statutory language and case law. The specific implementation program will vary from one community to the next depending on opportunities and constraints to development, legal and political acceptance. Major Findings: The problems of sprawl and strip commercial development are well known. The quality of life and efficiencies in a holistic, organic, ergonomic community have also been well known for centuries. Now, an integrated planning, legal and regulatory process has been developed to replace sprawl with a 21st century version of these communities. Conclusion: This project offers the opportunity to transform the urban landscape, and urban life, in the 21st century. The process is ready for implementation and the author invites inquiries from developers and communities.

Keywords: autonomous vehicles, community, home town, land use decision-making system, quality of life, sprawl, strip commercial

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Authors: Eric Morettin

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Cybersecurity and digital literacy are pressing issues among Canadian citizens, yet formal education does not provide today’s students with the necessary knowledge and skills needed to adapt to these challenging issues within the physical and digital labor-market. Canada’s current education systems do not highlight the importance of these respective fields, aside from using technology for learning management systems and alternative methods of assignment completion. Educators are not properly trained to integrate technology into the compulsory courses within public education, to better prepare their learners in these topics and Canada’s digital economy. ICTC addresses these gaps in education and training through cross-Canadian educational programming in digital literacy and competency, cybersecurity and coding which is bridged with Canada’s provincially regulated K-12 curriculum guidelines. After analyzing Canada’s provincial education, it is apparent that there are gaps in learning related to technology, as well as inconsistent educational outcomes that do not adequately represent the current Canadian and global economies. Presently only New Brunswick, Nova Scotia, Ontario, and British Columbia offer curriculum guidelines for cybersecurity, computer programming, and digital literacy. The remaining provinces do not address these skills in their curriculum guidelines. Moreover, certain courses across some provinces not being updated since the 1990’s. The three territories respectfully take curriculum strands from other provinces and use them as their foundation in education. Yukon uses all British Columbia curriculum. Northwest Territories and Nunavut respectfully use a hybrid of Alberta and Saskatchewan curriculum as their foundation of learning. Education that is provincially regulated does not allow for consistency across the country’s educational outcomes and what Canada’s students will achieve – especially when curriculum outcomes have not been updated to reflect present day society. Through this, ICTC has aligned Canada’s provincially regulated curriculum and created opportunities for focused education in the realm of technology to better serve Canada’s present learners and teachers; while addressing inequalities and applicability within curriculum strands and outcomes across the country. As a result, lessons, units, and formal assessment strategies, have been created to benefit students and teachers in this interdisciplinary, cross-curricular, practice - as well as meeting their compulsory education requirements and developing skills and literacy in cyber education. Teachers can access these lessons and units through ICTC’s website, as well as receive professional development regarding the assessment and implementation of these offerings from ICTC’s education coordinators, whose combines experience exceeds 50 years of teaching in public, private, international, and Indigenous schools. We encourage you to take this opportunity that will benefit students and educators, and will bridge the learning and curriculum gaps in Canadian education to better reflect the ever-changing public, social, and career landscape that all citizens are a part of. Students are the future, and we at ICTC strive to ensure their futures are bright and prosperous.

Keywords: cybersecurity, education, curriculum, teachers

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Authors: D. Pogliana, A. Maso, N. Milani, D. Panzin, S. Rivaroli, J. Konin

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This case aims to identify the role of movement quality during the final stage of return to sport (RTS) in a male amateur football player 13 years old after passing the acute phase of the bilateral Osgood-Schlatter disease (OSD). The patient, after a year from passing the acute phase of OSD with the abstention of physical activity, reports bilateral anterior knee pain at the beginning of the football sport activity. Interventions: After the orthopedist check, who recommended physiotherapy sessions for the correction of motor patterns and the isometric reinforcement of the muscles of the quadriceps, the rehabilitation intervention was developed in 7 weeks through 14 sessions of neuro-motor training (NMT) with a frequency of two weekly sessions and six sessions of muscle-strengthening with a frequency of one weekly session. The sessions of NMT were carried out through free body exercises (or with overloads) with visual bio-feedback with the help of two cameras (one with anterior vision and one with lateral vision of the subject) and a big touch screen. The aim of these sessions of NMT was to modify the dysfunctional motor patterns evaluated by the 2D motion analysis test. The test was carried out at the beginning and at the end of the rehabilitation course and included five movements: single-leg squat (SLS), drop jump (DJ), single-leg hop (SLH), lateral shuffle (LS), and change of direction (COD). Each of these movements was evaluated through the video analysis of dynamic valgus knee, pelvic tilt, trunk control, shock absorption, and motor strategy. A free image analysis software (Kinovea) was then used to calculate scores. Results: Baseline assessment of the subject showed a total score of 59% on the right limb and 64% on the left limb (considering an optimal score above 85%) with large deficits in shock absorption capabilities, the presence of dynamic valgus knee, and dysfunctional motor strategies defined “quadriceps dominant.” After six weeks of training, the subject achieved a total score of 80% on the right limb and 86% on the left limb, with significant improvements in shock absorption capabilities, the presence of dynamic knee valgus, and the employment of more hip-oriented motor strategies on both lower limbs. The improvements shown in dynamic knee valgus, greater hip-oriented motor strategies, and improved shock absorption identified through six weeks of the NMT program can help a teenager amateur football player to manage the anterior knee pain during sports activity. In conclusion, NMT was a good choice to help a 13 years old male amateur football player to return to performance without pain after OSD and can also be used with all this type of athletes of the other teams' sports.

Keywords: movement analysis, neuro-motor training, knee pain, movement strategies

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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: Laura Butabayeva, Svetlana Ismagulova, Gulbarshin Nogaibayeva, Maiya Temirbayeva, Aidana Zhussip

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The article presents the main results of the study conducted within the grant project «Organizational and methodological foundations for ensuring the inclusiveness of school students’ career guidance» (2022-2024). The main aim of the project is to study the issue of the absence of developed mechanisms, coordinating the activities of all stakeholders in preparing school students for conscious career choice, taking into account their individual opportunities and special educational needs. To achieve the aim of the project, according to the implementation plan, the analysis of foreign and national literature on the studied problem, as well as the study of the state of school students’ career guidance and their socialization in the context of inclusive education were conducted, the international experience on this issue was explored. The analysis of the national literature conducted by the authors has shown the State’s annual increase in the number of students with special educational needs as well as the rapid demand of labour market, influencing their professional self-determination in modern society. The participants from 5 State’s regions, including students, their parents, general secondary schools administration and educators, as well as employers, took part in the study, taking into account the geographical location: south, north, west, centre, and the cities of republican significance. To ensure the validity of the study’s results, the triangulation method was utilised, including both qualitative and quantitative methods. The data were analysed independently and compared with each other. Ethical principles were considered during all stages of the study. The characteristics of the system of career guidance in the modern school, the role and the involvement of stakeholders in the system of career guidance, the opinions of educators on school students’ preparedness for career choice, and the factors impeding the effectiveness of career guidance in schools were examined. The problem of stakeholders’ disunity and inconsistency, causing the systemic labor market distortions, the growth of low-skilled labor, and the unemployed, including people with special educational needs, were revealed. The other issue identified by the researchers was educators’ insufficient readiness for students’ career choice preparation in the context of inclusive education. To study cutting-edge experience in organizing a system of career guidance for young people and develop mechanisms coordinating the actions of all stakeholders in preparing students for career choice, the institutions of career guidance in France, Japan, and Germany were explored by the researchers. To achieve the aim of the project, the systemic contemporary model of school students’ professional self-determination, considering their individual opportunities and special educational needs, has been developed based on the study results and international experience. The main principles of this model are consistency, accessibility, inclusiveness, openness, coherence, continuity. The perspectives of students’ career guidance development in the context of inclusive education have been suggested.

Keywords: career guidance, inclusive education, model of school students’ professional self-determination, psychological and pedagogical support, special educational needs

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Authors: Dipendra Kumar Yadav, Nabaraj Paudel, Anjana Yadav

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Background: Low Birth weight (LBW) is defined as the weight at birth less than 2500 grams, irrespective of the period of their gestation. LBW is an important indicator of general health status of population and is considered as the single most important predictors of infant mortality especially of deaths within the first month of life that is birth weight determines the chances of newborn survival. Objective of this study was to identify the maternal risk factors associated with low birth weight neonates. Materials and Methods: A hospital based case-control study was conducted in maternity ward of Manipal Teaching Hospital, Pokhara, Nepal from 23 September 2014 to 12 November 2014. During study period 59 cases were obtained and twice number of control group were selected with frequency matching of the mother`s age with ± 3 years and total controls were 118. Interview schedule was used for data collection along with record review. Data were entered in Epi-data program and analysis was done with help of SPSS software program. Results: From bivariate logistic regression analysis, eighteen variables were found significantly associated with LBW and these were place of residence, family monthly income, education, previous still birth, previous LBW, history of STD, history of vaginal bleeding, anemia, ANC visits, less than four ANC visits, de-worming status, counseling during pregnancy, CVD, physical workload, stress, extra meal during pregnancy, smoking and alcohol consumption status. However after adjusting confounding variables, only six variables were found significantly associated with LBW. Mothers who had family monthly income up to ten thousand rupees were 4.83 times more likely to deliver LBW with CI (1.5-40.645) and p value 0.014 compared to mothers whose family income NRs.20,001-60,000. Mothers who had previous still birth were 2.01 times more likely to deliver LBW with CI (0.69-5.87) and p value 0.02 compared to mothers who did not has previous still birth. Mothers who had previous LBW were 5.472 times more likely to deliver LBW with CI (1.2-24.93) and p value 0.028 compared to mothers who did not has previous LBW. Mothers who had anemia during pregnancy were 3.36 times more likely to deliver LBW with CI (0.77-14.57) and p value 0.014 compared to mothers who did not has anemia. Mothers who delivered female newborn were 2.96 times more likely to have LBW with 95% CI (1.27-7.28) and p value 0.01 compared to mothers who deliver male newborn. Mothers who did not get extra meal during pregnancy were 6.04 times more likely to deliver LBW with CI (1.11-32.7) and p value 0.037 compared to mothers who getting the extra meal during pregnancy. Mothers who consumed alcohol during pregnancy were 4.83 times more likely to deliver LBW with CI (1.57-14.83) and p value 0.006 compared to mothers who did not consumed alcohol during pregnancy. Conclusions: To reduce low birth weight baby through economic empowerment of family and individual women. Prevention and control of anemia during pregnancy is one of the another strategy to control the LBW baby and mothers should take full dose of iron supplements with screening of haemoglobin level. Extra nutritional food should be provided to women during pregnancy. Health promotion program will be focused on avoidance of alcohol and strengthen of health services that leads increasing use of maternity services.

Keywords: low birth weight, case-control, risk factors, hospital based study

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Authors: Zia Ul Haq, Saleem Muhammad, Naeem Ullah, Abbas Shah, Abdullah Shah

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Pakistan being the developing country is facing double burden of communicable and non-communicable disease. The aspect of secondary prevention of ischemic heart disease in developing countries is the dire need for public health specialists, clinicians and policy makers. There is some evidence that psychotherapeutic measures, including psychotherapy, recreation, exercise and stress management training have positive impact on secondary prevention of cardiovascular diseases but there are some contradictory findings as well. Cardiac rehabilitation program (CRP) has not yet fully implemented in Pakistan. Psychological, physical and specific health-related quality of life (HRQoL) outcomes needs assessment with respect to its practicality, effectiveness, and success. Objectives: To determine the effect of cardiac rehabilitation program (CRP) on the health-related quality of life (HRQoL) measures of post MI patients compared to the usual care. Hypothesis: Post MI patients who receive the interventions (CRP) will have better HRQoL as compared to those who receive the usual cares. Methods: The randomized control trial was conducted at a Cardiac Rehabilitation Unit of Lady Reading Hospital (LRH), Peshawar. LRH is the biggest hospital of the Province Khyber Pakhtunkhwa (KP). A total 206 participants who had recent first myocardial infarction were inducted in the study. Participants were randomly allocated into two group i.e. usual care group (UCG) and cardiac rehabilitation group (CRG) by permuted-block randomization (PBR) method. CRP was conducted in CRG in two phases. Three HRQoL outcomes i.e. general health questionnaire (GHQ), self-rated health (SRH) and MacNew quality of life after myocardial infarction (MacNew QLMI) were assessed at baseline and follow-up visits among both groups. Data were entered and analyzed by appropriate statistical test in STATA version 12. Results: A total of 195 participants were assessed at the follow-up period due to lost-to-follow-up. The mean age of the participants was 53.66 + 8.3 years. Males were dominant in both groups i.e. 150 (76.92%). Regarding educational status, majority of the participants were illiterate in both groups i.e. 128 (65.64%). Surprisingly, there were 139 (71.28%) who were non-smoker on the whole. The comorbid status was positive in 120 (61.54%) among all the patients. The SRH at follow-up among UCG and CRG was 4.06 (95% CI: 3.93, 4.19) and 2.36 (95% CI: 2.2, 2.52) respectively (p<0.001). GHQ at the follow-up of UCG and CRG was 20.91 (95% CI: 18.83, 21.97) and 7.43 (95% CI: 6.59, 8.27) respectively (p<0.001). The MacNew QLMI at follow-up of UCG and CRG was 3.82 (95% CI: 3.7, 3.94) and 5.62 (95% CI: 5.5, 5.74) respectively (p<0.001). All the HRQoL measures showed strongly significant improvement in the CRG at follow-up period. Conclusion: HRQOL improved in post MI patients after comprehensive CRP. Education of the patients and their supervision is needed when they are involved in their rehabilitation activities. It is concluded that establishing CRP in cardiac units, recruiting post-discharged MI patients and offering them CRP does not impose high costs and can result in significant improvement in HRQoL measures. Trial registration no: ACTRN12617000832370

Keywords: cardiovascular diseases, cardiac rehabilitation, health-related quality of life, HRQoL, myocardial infarction, quality of life, QoL, rehabilitation, randomized control trial

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Authors: Zo Hasina Rabemananjara

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The North-East of Madagascar is the pillar of Madagascar's foreign trade, providing 41% and 80% of world exports of cloves and vanilla, respectively, in 2016. For Madagascar, the north-eastern escarpment is home to the last massifs of humid forest in large scale of the island, surrounded by a small scale agricultural mosaic. In the sites where this study is taking place, located in the peripheral zones of protected areas, the production of rent aims to supply international markets. In fact, importers of the cash crops produced in these areas are located mainly in India, Singapore, France, Germany and the United States. Recently, the price of these products has increased significantly, especially from the year 2015. For vanilla, the price has skyrocketed, from an approximate price of 73 USD per kilo in 2015 to more than 250 USD per kilo in 2016. The value of clove exports increased sharply by 49.4% in 2017, largely to Singapore and India due to the sharp increase in exported volume (+47, 6%) in 2017. If the relationship between the rise in prices of rented products and the change in physical environments is known, the evolution of the behavior of land users linked to this aspect was not yet addressed by research. In fact, the consequence of this price increase in the organization of the use of space at the local level still raises questions. Hence, the research question is: to what extent does this improvement in the price of imported products affect user behavior linked to the local organization of access to the factor of soil production? To fully appreciate this change in behavior, surveys of 144 land user households were carried out, and group interviews were also carried out. The results of this research showed that the rise in the prices of annuity products from the year 2015 caused significant changes in the behavior of land users in the study sites. Young people, who have not been attracted to farming for a long time, have started to show interest in it since the period of rising vanilla and clove prices. They have set up their own fields of vanilla and clove cultivation. This revival of interest conferred an important value on the land and caused conflicts especially between family members because the acquisition of the cultivated land was done by inheritance or donation. This change in user behavior has also affected the farmers' life strategy since the latter have decided to abandon rain-fed rice farming, which has long been considered a guaranteed subsistence activity for cash crops. This research will contribute to nourishing scientific reflection on the management of land use and also to support political decision-makers in decision-making on spatial planning.

Keywords: behavior of land users, North-eastern Madagascar, price of export products, spatial planning

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Authors: Dahunsi Michael Oluseyi

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This paper aims to extensively examine eco-city planning and urban design in Lagos, Nigeria. It will delve into the city's developments, challenges, and potential solutions to offer insights for sustainable urban growth within the rapidly expanding urban landscape. The research will scrutinize recent innovations, emerging trends, and practical remedies to promote ecological sustainability within an urban framework. It will encompass a more in-depth review of current literature, case studies, and qualitative analyses, thereby augmenting the depth and breadth of the research. The objectives are to assess the current eco-city planning initiatives and urban design trends in Lagos, Nigeria, considering the city's unique characteristics and challenges. To identify and analyze the challenges encountered during the implementation of eco-friendly urban developments in Lagos, to explore and evaluate the innovative and practical solutions that are implemented to promote sustainability within the city, to provide comprehensive insights and actionable recommendations for policymakers, urban planners, and other stakeholders involved in sustainable urban development in Lagos, the rapid urbanization of Lagos has brought forth a myriad of challenges, including a burgeoning population, inadequate infrastructure, waste management issues, and environmental pollution. Eco-city planning has emerged as a promising approach to addressing these obstacles, striving to create urban spaces that are more habitable, resource-efficient, and environmentally friendly. This research holds substantial importance in exploring the application of eco-city planning principles within a megacity like Lagos. Analyzing recent innovations, trends, concerns, challenges, and solutions provides invaluable insights for policymakers, urban planners, and stakeholders dedicated to fostering sustainable urban development. The methodologies employed in this research are structured to embrace a multifaceted and intricate approach, aiming to facilitate a comprehensive understanding of the complexities inherent in eco-city planning and urban design in Lagos, Nigeria. This methodological framework is designed to encompass various diverse strategies and analytical tools to effectively capture the multidimensional aspects of sustainable urban development. It involves an in-depth analysis of academic publications, governmental reports, and urban planning documents to highlight global eco-city planning trends and gather Lagos-specific insights through a detailed exploration of eco-friendly initiatives and projects in Lagos to evaluate successes, challenges, and strategies for addressing environmental concerns by engaging key stakeholders, including urban planners, policymakers, environmental experts, and residents, to collect firsthand perspectives, concerns, and insights. Also, a thorough analysis will be carried out on data collected from literature reviews, case studies, interviews, and surveys used to extract prevalent patterns, challenges, and innovative solutions from diverse sources. This study aims to contribute to the discourse on sustainable urban development by offering a comprehensive analysis of eco-city planning in Lagos and providing practical recommendations for a more sustainable urban future.

Keywords: eco-friendly, innovation, sustainability, stakeholders

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Authors: Mark Kennedy, E. Bantugon, Noruane A. Daileg

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Leaks arising from aircraft fuel tanks is a protracted problem for the aircraft manufacturers, operators, and maintenance crews. It principally arises from stress, structural defects, or degraded sealants as the aircraft age. It can be ignited by different sources, which can result in catastrophic flight and consequences, exhibiting a major drain both on time and budget. In order to mitigate and eliminate this kind of problem, the researcher produced an experimental sealant having a base material of natural tree resin, the Pili Tree Resin. Aside from producing an experimental sealant, the main objective of this research is to analyze its physical, chemical, mechanical, thermal, and rheological properties, which is beneficial and effective for specific aircraft parts, particularly the integral fuel tank. The experimental method of research was utilized in this study since it is a product invention. This study comprises two parts, specifically the Optimization Process and the Characterization Process. In the Optimization Process, the experimental sealant was subjected to the Flammability Test, an important test and consideration according to 14 Code of Federal Regulation Appendix N, Part 25 - Fuel Tank Flammability Exposure and Reliability Analysis, to get the most suitable formulation. Followed by the Characterization Process, where the formulated experimental sealant has undergone thirty-eight (38) different standard testing including Organoleptic, Instrumental Color Measurement Test, Smoothness of Appearance Test, Miscibility Test, Boiling Point Test, Flash Point Test, Curing Time, Adhesive Test, Toxicity Test, Shore A Hardness Test, Compressive Strength, Shear Strength, Static Bending Strength, Tensile Strength, Peel Strength Test, Knife Test, Adhesion by Tape Test, Leakage Test), Drip Test, Thermogravimetry-Differential Thermal Analysis (TG-DTA), Differential Scanning Calorimetry, Calorific Value, Viscosity Test, Creep Test, and Anti-Sag Resistance Test to determine and analyze the five (5) material properties of the sealant. The numerical values of the mentioned tests are determined using product application, testing, and calculation. These values are then used to calculate the efficiency of the experimental sealant. Accordingly, this efficiency is the means of comparison between the experimental and commercial sealant. Based on the results of the different standard testing conducted, the experimental sealant exceeded all the data results of the commercial sealant. This result shows that the physicochemical-mechanical, thermal, and rheological properties of the experimental sealant are far more effective as an aircraft integral fuel tank sealant alternative in comparison to the commercial sealant. Therefore, Pili Tree possesses a new role and function: a source of ingredients in sealant production.

Keywords: Aircraft Integral Fuel Tank, Physicochemi-mechanical, Pili Tree Resin, Properties, Rheological, Sealant, Thermal

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Authors: Teng Li, Kamran Mohseni

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This paper presents an inviscid regularization technique for the incompressible two-phase flow simulations. This technique is known as observable method due to the understanding of observability that any feature smaller than the actual resolution (physical or numerical), i.e., the size of wire in hotwire anemometry or the grid size in numerical simulations, is not able to be captured or observed. Differ from most regularization techniques that applies on the numerical discretization, the observable method is employed at PDE level during the derivation of equations. Difficulties in the simulation and analysis of realistic fluid flow often result from discontinuities (or near-discontinuities) in the calculated fluid properties or state. Accurately capturing these discontinuities is especially crucial when simulating flows involving shocks, turbulence or sharp interfaces. Over the past several years, the properties of this new regularization technique have been investigated that show the capability of simultaneously regularizing shocks and turbulence. The observable method has been performed on the direct numerical simulations of shocks and turbulence where the discontinuities are successfully regularized and flow features are well captured. In the current paper, the observable method will be extended to two-phase interfacial flows. Multiphase flows share the similar features with shocks and turbulence that is the nonlinear irregularity caused by the nonlinear terms in the governing equations, namely, Euler equations. In the direct numerical simulation of two-phase flows, the interfaces are usually treated as the smooth transition of the properties from one fluid phase to the other. However, in high Reynolds number or low viscosity flows, the nonlinear terms will generate smaller scales which will sharpen the interface, causing discontinuities. Many numerical methods for two-phase flows fail at high Reynolds number case while some others depend on the numerical diffusion from spatial discretization. The observable method regularizes this nonlinear mechanism by filtering the convective terms and this process is inviscid. The filtering effect is controlled by an observable scale which is usually about a grid length. Single rising bubble and Rayleigh-Taylor instability are studied, in particular, to examine the performance of the observable method. A pseudo-spectral method is used for spatial discretization which will not introduce numerical diffusion, and a Total Variation Diminishing (TVD) Runge Kutta method is applied for time integration. The observable incompressible Euler equations are solved for these two problems. In rising bubble problem, the terminal velocity and shape of the bubble are particularly examined and compared with experiments and other numerical results. In the Rayleigh-Taylor instability, the shape of the interface are studied for different observable scale and the spike and bubble velocities, as well as positions (under a proper observable scale), are compared with other simulation results. The results indicate that this regularization technique can potentially regularize the sharp interface in the two-phase flow simulations

Keywords: Euler equations, incompressible flow simulation, inviscid regularization technique, two-phase flow

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Authors: Elena Selezneva

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Over the last two decades, an unprecedented growth in uncertainty and volatility in all aspects of the business environment has caused major global supply chain disruptions and malfunctions. The effects of one failed company in a supply chain can ripple up and down the chain, causing a number of entities or an entire supply chain to collapse. The complicating factor is that an increasingly unstable and unpredictable business environment fuels the growing complexity of global supply chain networks. That makes supply chain operations extremely unpredictable and hard to manage with the established methods and strategies. It has caused the premature demise of many companies around the globe as they could not withstand or adapt to the storm of change. Solutions to this problem are not easy to come by. There is a lack of new empirically tested theories and practically viable supply chain resilience strategies. The mainstream organizational approach to managing supply chain resilience is rooted in well-established theories developed in the 1960-1980s. However, their effectiveness is questionable in currently extremely volatile business environments. The systems thinking approach offers an alternative view of supply chain resilience. Still, it is very much in the development stage. The aim of this explorative research is to investigate supply chain management strategies that are successful in taming complexity in volatile business environments and creating resilience in supply chains. The design of this research methodology was guided by an interpretivist paradigm. A literature review informed the selection of the systems thinking approach to supply chain resilience. Therefore, an explorative single case study of Ventilator Challenge UK was selected as a case study for its extremely resilient performance of its supply chain during a period of national crisis. Ventilator Challenge UK is intensive care ventilators supply project for the NHS. It ran for 3.5 months and finished in 2020. The participants moved on with their lives, and most of them are not employed by the same organizations anymore. Therefore, the study data includes documents, historical interviews, live interviews with participants, and social media postings. The data analysis was accomplished in two stages. First, data were thematically analyzed. In the second stage, pattern matching and pattern identification were used to identify themes that formed the findings of the research. The findings from the Ventilator Challenge UK case study supply management practices demonstrated all the features of an adaptive dynamic system. They cover all the elements of supply chain and employ an entire arsenal of adaptive dynamic system strategies enabling supply chain resilience. Also, it is not a simple sum of parts and strategies. Bonding elements and connections between the components of a supply chain and its environment enabled the amplification of resilience in the form of systemic emergence. Enablers are categorized into three subsystems: supply chain central strategy, supply chain operations, and supply chain communications. Together, these subsystems and their interconnections form the resilient supply chain system framework conceptualized by the author.

Keywords: enablers of supply chain resilience, supply chain resilience strategies, systemic approach in supply chain management, resilient supply chain system framework, ventilator challenge UK

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Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

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Authors: Dian Zhang, Brendan Heery, Maria O’Neill, Ciprian Briciu-Burghina, Noel E. O’Connor, Fiona Regan

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Recent developments in sensors, wireless data communication and the cloud computing have brought the sensor web to a whole new generation. The introduction of the concept of ‘Internet of Thing (IoT)’ has brought the sensor research into a new level, which involves the developing of long lasting, low cost, environment friendly and smart sensors; new wireless data communication technologies; big data analytics algorithms and cloud based solutions that are tailored to large scale smart sensor network. The next generation of smart sensor network consists of several layers: physical layer, where all the smart sensors resident and data pre-processes occur, either on the sensor itself or field gateway; data transmission layer, where data and instructions exchanges happen; the data process layer, where meaningful information is extracted and organized from the pre-process data stream. There are many definitions of smart sensor, however, to summarize all these definitions, a smart sensor must be Intelligent and Adaptable. In future large scale sensor network, collected data are far too large for traditional applications to send, store or process. The sensor unit must be intelligent that pre-processes collected data locally on board (this process may occur on field gateway depends on the sensor network structure). In this case study, three smart sensing methods, corresponding to simple thresholding, statistical model and machine learning based MoPBAS method, are introduced and their strength and weakness are discussed as an introduction to the smart sensing concept. Data fusion, the integration of data and knowledge from multiple sources, are key components of the next generation smart sensor network. For example, in the water level monitoring system, weather forecast can be extracted from external sources and if a heavy rainfall is expected, the server can send instructions to the sensor notes to, for instance, increase the sampling rate or switch on the sleeping mode vice versa. In this paper, we describe the deployment of 11 affordable water level sensors in the Dublin catchment. The objective of this paper is to use the deployed river level sensor network at the Dodder catchment in Dublin, Ireland as a case study to give a vision of the next generation of a smart sensor network for flood monitoring to assist agencies in making decisions about deploying resources in the case of a severe flood event. Some of the deployed sensors are located alongside traditional water level sensors for validation purposes. Using the 11 deployed river level sensors in a network as a case study, a vision of the next generation of smart sensor network is proposed. Each key component of the smart sensor network is discussed, which hopefully inspires the researchers who are working in the sensor research domain.

Keywords: smart sensing, internet of things, water level sensor, flooding

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: Quentin C.P. Bourgogne, Vanessa Bouchart, Pierre Chevrier, Emmanuel Dattoli

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This study presents an experimental and theoretical work conducted on a PolyPhenylene Sulfide reinforced with 40%wt of short glass fibers (PPS GF40) and its matrix. Thermoplastics are widely used in the automotive industry to lightweight automotive parts. The replacement of metallic parts by thermoplastics is reaching under-the-hood parts, near the engine. In this area, the parts are subjected to high temperatures and are immersed in cooling liquid. This liquid is composed of water and glycol and can affect the mechanical properties of the composite. The aim of this work was thus to quantify the evolution of mechanical properties of the thermoplastic composite, as a function of temperature and liquid aging effects, in order to develop a reliable design of parts. An experimental campaign in the tensile mode was carried out at different temperatures and for various glycol proportions in the cooling liquid, for monotonic and cyclic loadings on a neat and a reinforced PPS. The results of these tests allowed to highlight some of the main physical phenomena occurring during these solicitations under tough hydro-thermal conditions. Indeed, the performed tests showed that temperature and liquid cooling aging can affect the mechanical behavior of the material in several ways. The more the cooling liquid contains water, the more the mechanical behavior is affected. It was observed that PPS showed a higher sensitivity to absorption than to chemical aggressiveness of the cooling liquid, explaining this dominant sensitivity. Two kinds of behaviors were noted: an elasto-plastic type under the glass transition temperature and a visco-pseudo-plastic one above it. It was also shown that viscosity is the leading phenomenon above the glass transition temperature for the PPS and could also be important under this temperature, mostly under cyclic conditions and when the stress rate is low. Finally, it was observed that soliciting this composite at high temperatures is decreasing the advantages of the presence of fibers. A new phenomenological model was then built to take into account these experimental observations. This new model allowed the prediction of the evolution of mechanical properties as a function of the loading environment, with a reduced number of parameters compared to precedent studies. It was also shown that the presented approach enables the description and the prediction of the mechanical response with very good accuracy (2% of average error at worst), over a wide range of hydrothermal conditions. A temperature-humidity equivalence principle was underlined for the PPS, allowing the consideration of aging effects within the proposed model. Then, a limit of improvement of the reachable accuracy was determinate for all models using this set of data by the application of an artificial intelligence-based model allowing a comparison between artificial intelligence-based models and phenomenological based ones.

Keywords: aging, analytical modeling, mechanical testing, polymer matrix composites, sequential model, thermomechanical

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Authors: Ekaterina Malova

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Type 1 diabetes (T1D) is a chronic illness requiring immense lifestyle changes to reduce the chance of life-threatening complications. Moving to a college may be the first time for a young adult with T1D to take responsibility for all the aspects of their diabetes care. In addition, people with T1D constantly face stigmatization and discrimination as a result of their health condition, which puts additional pressure on young adults with T1D. Hence, omissions in diabetes self-care often occur during the time of transition to college when both the social and physical environment of young adults changes drastically and contribute to the fact that emerging young adults remain one of the age groups with the highest hemoglobin levels and poorest diabetes control. However, despite potential severe health risks caused by a lack of proper diabetes self-care, little is known about the experiences of emerging adults embarking on a higher education journey as this population. Thus, young adults with type 1 diabetes are a 'forgotten group,' meaning that their experiences are rarely addressed by researchers. Given that self-disclosure and information-seeking can be challenging for individuals with stigmatized illnesses, online platforms like YouTube have become a popular medium of self-disclosure and information-seeking for people living with T1D. Thus, this study aims to provide an analysis of experiences that college students with T1D choose to share with the general public online and explore the nature of information being communicated by college students with T1D to the online community in personal narratives posted on YouTube. A systematic approach was used to retrieve a video sample by searching YouTube with keywords 'type 1 diabetes' and 'college,' with results ordered by relevance. A total of 18 videos were saved. Video lengths ranged from 2 to 28 minutes. The data were coded using NVivo. Video transcripts were coded and analyzed utilizing the thematic analysis method. Three key themes emerged from thematic analysis: 1) Advice, 2) Personal experience, and 3) Things I wish everyone knew about T1D. In addition, Theme 1 was divided into subtopics to differentiate between the most common types of advice: 1) Overcoming stigma and b) Seeking social support. The identified themes indicate that two groups of the population can potentially benefit from watching students’ video testimonies: 1) lay public and 2) other students with T1D. Given that students in the videos reported a lack of T1D education in the lay public, such video narratives can serve important educational purposes and reduce health stigma, while perceived similarity and identification with students in the videos may facilitate the transition of health information to other individuals with T1D and positively affect their diabetes routine. Thus, online video narratives can potentially serve both educational and persuasive purposes, empowering students with T1D to stay in control of T1D while succeeding academically.

Keywords: type 1 diabetes, college students, health communication, transition period

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Authors: Muccifora S., Rinallo C., Bellani L.

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Calcium (Ca²+) is an element essential to the plant being involved in plant growth and development. At high concentrations, it is toxic and can influence every stage, process and cellular activity of plant life. Given its toxicity, cells implement mechanisms to compartmentalize calcium in a vacuole, endoplasmic reticulum, mitochondria, plastids and cell wall. One of the most effective mechanisms to reduce the excess of calcium, thus avoiding cellular damage, is its complexation with oxalic acid to form calcium oxalate crystals that are no longer osmotically or physiologically active. However, the sequestered calcium can be mobilized when the plant needs it. Calcium crystals can be accumulated in the vacuole of specialized sink-cells called idioblasts, with different crystalline forms (druse, raphyde and styloid) of diverse physiological meanings. Actinidia deliciosa cv. Hayward presents raphydes and styloid localized in idioblasts in cells of photosynthetic and non-photosynthetic tissues. The purpose of this work was to understand if there is a relationship between the age of Actinidia leaves and the presence, distribution, dimension and shape of oxalate crystals by means of light, fluorescent, polarized and transmission electron microscopy. Three vines from female plants were chosen at the beginning of the season and used throughout the study. The leaves with petioles were collected at various stages of development from the bottom to the shoot of the plants monthly from April to July. The samples were taken in corresponding areas of the central and lateral parts of the leaves and of the basal portion of the petiole. The results showed that in the leaves, the number of raphyde idioblasts decreased with the progress of the growing season, while the styloid idioblasts increased progressively, becoming very numerous in the upper nodes of July. In June and in July samples, in the vacuoles of the highest nodes, a portion regular in shape strongly stained with rubeanic acid was present. Moreover, the chlortetracycline (CTC) staining for localization of free calcium marked the wall of the idioblasts and the wall of the cells near vascular bundles. In April petiole samples, moving towards the youngest nodes, the raphydes idioblast decreased in number and in the length of the single raphydes. Besides, crystals stained with rubeanic acid appeared in the vacuoles of some cells. In June samples, numerous raphyde idioblasts oriented parallel to vascular bundles were evident. Under the electron microscope, numerous idioblasts presented not homogeneous electrondense aggregates of material, in which a few crystals (styloids) in the form of regular holes were scattered. In July samples, an increase in the number of styloid idioblasts in the youngest nodes and little masses stained with CTC near styloids were observed. Peculiar cells stained with rubeanic acid were detected and hypothesized to be involved in the formation of the idioblasts. In conclusion, in Actinidia leaves and petioles, it seems to confirm the hypothesis that the formation of styloid idioblasts can be correlated to increasing calcium levels in growing tissues.

Keywords: calcium oxalate crystals, actinidia deliciosa, light and electron microscopy, idioblasts

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Authors: Laura M. F. Bertens

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The houses we inhabit are important containers of memory. As homes, they take on meaning for those who live inside, and memories of family life become intimately tied up with rooms, windows, and gardens. Each new family creates a new layer of meaning, resulting in a palimpsest of family memory. These houses function quite literally as memory palaces, as a walk through a childhood home will show; each room conjures up images of past events. Over time, these personal memories become woven together with the cultural memory of countries and generations. The importance of the home is a central theme in art, and several contemporary artists have a special interest in the relationship between memory and the home. This paper analyses three case studies in order to get a deeper understanding of the ways in which the home functions and feels like a memory palace, both on an individual and on a collective, cultural level. Close reading of the artworks is performed on the theoretical intersection between Art History and Cultural Memory Studies. The first case study concerns works from the exhibition Mnemosyne by the artist duo Anne and Patrick Poirier. These works combine interests in architecture, archaeology, and psychology. Models of cities and fantastical architectural designs resemble physical structures (such as the brain), architectural metaphors used in representing the concept of memory (such as the memory palace), and archaeological remains, essential to our shared cultural memories. Secondly, works by Do Ho Suh will help us understand the relationship between the home and memory on a far more personal level; outlines of rooms from his former homes, made of colourful, transparent fabric and combined into new structures, provide an insight into the way these spaces retain individual memories. The spaces have been emptied out, and only the husks remain. Although the remnants of walls, light switches, doors, electricity outlets, etc. are standard, mass-produced elements found in many homes and devoid of inherent meaning, together they remind us of the emotional significance attached to the muscle memory of spaces we once inhabited. The third case study concerns an exhibition in a house put up for sale on the Dutch real estate website Funda. The house was built in 1933 by a Jewish family fleeing from Germany, and the father and son were later deported and killed. The artists Anne van As and CA Wertheim have used the history and memories of the house as a starting point for an exhibition called (T)huis, a combination of the Dutch words for home and house. This case study illustrates the way houses become containers of memories; each new family ‘resets’ the meaning of a house, but traces of earlier memories remain. The exhibition allows us to explore the transition of individual memories into shared cultural memory, in this case of WWII. Taken together, the analyses provide a deeper understanding of different facets of the relationship between the home and memory, both individual and collective, and the ways in which art can represent these.

Keywords: Anne and Patrick Poirier, cultural memory, Do Ho Suh, home, memory palace

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Authors: Marcelo Lopes Dias Kolling, Felipe Ferreira Laranjeira, Guilherme Augusto Hettwer, Pedro Salomão Piccinini, Marwan Masri, Carlos Oscar Uebel

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Introduction: Injectable fillers are among the most common nonsurgical cosmetic procedures, with significant growth yearly. Knowledge of rheological and mechanical characteristics of fillers, facial anatomy, and injection technique is essential for safety. Concepts such as the use of cannula versus needle, aspiration before injection, and facial danger zones have been well discussed. In case of an accidental intravascular puncture, the pressure inside the vessel may not be sufficient to push blood into the syringe due to the characteristics of the filler product; this is especially true for calcium hydroxyapatite (CaHA) or hyaluronic acid (HA) fillers with high G’. Since viscoelastic properties of normal saline are much lower than those of fillers, aspiration with saline prior to filler injection may decrease the risk of a false negative aspiration and subsequent catastrophic effects. We discuss a technique to add an additional safety step to the procedure with saline aspiration prior to injection, a ‘’reverse Seldinger’’ technique for intravascular access, which we term SANIT: Saline Aspiration Negative Intravascular Test. Objectives: To demonstrate the author’s (PSP) technique which adds an additional safety step to the process of filler injection, with both CaHA and HA, in order to decrease the risk of intravascular injection. Materials and Methods: Normal skin cleansing and topical anesthesia with prilocaine/lidocaine cream are performed; the facial subunits to be treated are marked. A 3mL Luer lock syringe is filled with 2mL of 0.9% normal saline and a 27G needle, which is turned one half rotation. When a cannula is to be used, the Luer lock syringe is attached to a 27G 4cm single hole disposable cannula. After skin puncture, the 3mL syringe is advanced with the plunger pulled back (negative pressure). Progress is made to the desired depth, all the while aspirating. Once the desired location of filler injection is reached, the syringe is exchanged for the syringe containing a filler, securely grabbing the hub of the needle and taking care to not dislodge the needle tip. Prior to this, we remove 0.1mL of filler to allow for space inside the syringe for aspiration. We again aspirate and inject retrograde. SANIT is especially useful for CaHA, since the G’ is much higher than HA, and thus reflux of blood into the syringe is less likely to occur. Results: The technique has been used safely for the past two years with no adverse events; the increase in cost is negligible (only the cost of 2mL of normal saline). Over 100 patients (over 300 syringes) have been treated with this technique. The risk of accidental intravascular puncture has been calculated to be between 1:6410 to 1:40882 syringes among expert injectors; however, the consequences of intravascular injection can be catastrophic even with board-certified physicians. Conclusions: While the risk of intravascular filler injection is low, the consequences can be disastrous. We believe that adding the SANIT technique can help further mitigate risk with no significant untoward effects and could be considered by all performing injectable fillers. Further follow-up is ongoing.

Keywords: injectable fillers, safety, saline aspiration, injectable filler complications, hyaluronic acid, calcium hydroxyapatite

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Authors: Jan Masak, Eva Kvasnickova, Vladimir Scholtz, Olga Matatkova, Marketa Valkova, Alena Cejkova

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Microbial colonization of medical instruments, catheters, implants, etc. is a serious problem in the spread of nosocomial infections. Biofilms exhibit enormous resistance to environment. The resistance of biofilm populations to antibiotic or biocides often increases by two to three orders of magnitude in comparison with suspension populations. Subjects of interests are substances or physical processes that primarily cause the destruction of biofilm, while the released cells can be killed by existing antibiotics. In addition, agents that do not have a strong lethal effect do not cause such a significant selection pressure to further enhance resistance. Non-thermal plasma (NTP) is defined as neutral, ionized gas composed of particles (photons, electrons, positive and negative ions, free radicals and excited or non-excited molecules) which are in permanent interaction. In this work, the effect of NTP generated by the cometary corona with a metallic grid on the formation and stability of biofilm and metabolic activity of cells in biofilm was studied. NTP was applied on biofilm populations of Staphylococcus epidermidis DBM 3179, Pseudomonas aeruginosa DBM 3081, DBM 3777, ATCC 15442 and ATCC 10145, Escherichia coli DBM 3125 and Candida albicans DBM 2164 grown on solid media on Petri dishes and on the titanium alloy (Ti6Al4V) surface used for the production joint replacements. Erythromycin (for S. epidermidis), polymyxin B (for E. coli and P. aeruginosa), amphotericin B (for C. albicans) and ceftazidime (for P. aeruginosa) were used to study the combined effect of NTP and antibiotics. Biofilms were quantified by crystal violet assay. Metabolic activity of the cells in biofilm was measured using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric test based on the reduction of MTT into formazan by the dehydrogenase system of living cells. Fluorescence microscopy was applied to visualize the biofilm on the surface of the titanium alloy; SYTO 13 was used as a fluorescence probe to stain cells in the biofilm. It has been shown that biofilm populations of all studied microorganisms are very sensitive to the type of used NTP. The inhibition zone of biofilm recorded after 60 minutes exposure to NTP exceeded 20 cm², except P. aeruginosa DBM 3777 and ATCC 10145, where it was about 9 cm². Also metabolic activity of cells in biofilm differed for individual microbial strains. High sensitivity to NTP was observed in S. epidermidis, in which the metabolic activity of biofilm decreased after 30 minutes of NTP exposure to 15% and after 60 minutes to 1%. Conversely, the metabolic activity of cells of C. albicans decreased to 53% after 30 minutes of NTP exposure. Nevertheless, this result can be considered very good. Suitable combinations of exposure time of NTP and the concentration of antibiotic achieved in most cases a remarkable synergic effect on the reduction of the metabolic activity of the cells of the biofilm. For example, in the case of P. aeruginosa DBM 3777, a combination of 30 minutes of NTP with 1 mg/l of ceftazidime resulted in a decrease metabolic activity below 4%.

Keywords: anti-biofilm activity, antibiotic, non-thermal plasma, opportunistic pathogens

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Authors: Elisavet Kechagia

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Due to the interplay of different genetic and environmental risk factors and its heterogeneous nature, the concept of attention deficit hyperactivity disorder (ADHD) has shaped controversy and conflicts, which have been, in turn, reflected in the controversial arguments about its treatment. Taking into account recent well evidence-based researches suggesting that ADHD is a condition, in which biopsychosocial factors are all weaved together, the current paper explores the multiple risk-factors that are likely to influence ADHD, with a particular focus on adolescents with ADHD who might experience comorbid social, emotional and behavioural disorders (SEBD). In the first section of this paper, the primary objective was to investigate the conflicting ideas regarding the definition, diagnosis and treatment of ADHD at an international level as well as to critically examine and identify the limitations of the two most prevailing sets of diagnostic criteria that inform current diagnosis, the American Psychiatric Association’s (APA) diagnostic scheme, DSM-V, and the World Health Organisation’s (WHO) classification of diseases, ICD-10. Taking into consideration the findings of current longitudinal studies on ADHD association with high rates of comorbid conditions and social dysfunction, in the second section the author moves towards an investigation of the transitional points −physical, psychological and social ones− that students with ADHD might experience during early adolescence, as informed by neuroscience and developmental contextualism theory. The third section is an exploration of the different perspectives of ADHD as reflected in individuals’ with ADHD self-reports and the KENT project’s findings on school staff’s attitudes and practices. In the last section, given the high rates of SEBDs in adolescents with ADHD, it is examined how cognitive behavioural therapy (CBT), coupled with other interventions, could be effective in ameliorating anti-social behaviours and/or other emotional and behavioral difficulties of students with ADHD. The findings of a range of randomised control studies indicate that CBT might have positive outcomes in adolescents with multiple behavioural problems, hence it is suggested to be considered both in schools and other community settings. Finally, taking into account the heterogeneous nature of ADHD, the different biopsychosocial and environmental risk factors that take place during adolescence and the discourse and practices concerning ADHD and SEBD, it is suggested how it might be possible to make sense of and meaningful improvements to the education of adolescents with ADHD within a multi-modal and multi-disciplinary whole-school approach that addresses the multiple problems that not only students with ADHD but also their peers might experience. Further research that would be based on more large-scale controls and would investigate the effectiveness of various interventions, as well as the profiles of those students who have benefited from particular approaches and those who have not, will generate further evidence concerning the psychoeducation of adolescents with ADHD allowing for generalised conclusions to be drawn.

Keywords: adolescence, attention deficit hyperctivity disorder, cognitive behavioural theory, comorbid social emotional behavioural disorders, treatment

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Authors: Laura C. Loaiza, Elodie Salager, Nicolas Louvain, Athmane Boulaoued, Antonella Iadecola, Patrik Johansson, Lorenzo Stievano, Vincent Seznec, Laure Monconduit

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Lithium-ion batteries (LIBs) have an important place among energy storage devices due to their high capacity and good cyclability. However, the advancements in portable and transportation applications have extended the research towards new horizons, and today the development is hampered, e.g., by the capacity of the electrodes employed. Silicon and germanium are among the considered modern anode materials as they can undergo alloying reactions with lithium while delivering high capacities. It has been demonstrated that silicon in its highest lithiated state can deliver up to ten times more capacity than graphite (372 mAh/g): 4200 mAh/g for Li₂₂Si₅ and 3579 mAh/g for Li₁₅Si₄, respectively. On the other hand, germanium presents a capacity of 1384 mAh/g for Li₁₅Ge₄, and a better electronic conductivity and Li ion diffusivity as compared to Si. Nonetheless, the commercialization potential of Ge is limited by its cost. The synergetic effect of Si₁₋ₓGeₓ alloys has been proven, the capacity is increased compared to Ge-rich electrodes and the capacity retention is increased compared to Si-rich electrodes, but the exact performance of this type of electrodes will depend on factors like specific capacity, C-rates, cost, etc. There are several reports on various formulations of Si₁₋ₓGeₓ alloys with promising LIB anode performance with most work performed on complex nanostructures resulting from synthesis efforts implying high cost. In the present work, we studied the electrochemical mechanism of the Si₀.₅Ge₀.₅ alloy as a realistic micron-sized electrode formulation using carboxymethyl cellulose (CMC) as the binder. A combination of a large set of in situ and operando techniques were employed to investigate the structural evolution of Si₀.₅Ge₀.₅ during lithiation and delithiation processes: powder X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), Raman spectroscopy, and 7Li solid state nuclear magnetic resonance spectroscopy (NMR). The results have presented a whole view of the structural modifications induced by the lithiation/delithiation processes. The Si₀.₅Ge₀.₅ amorphization was observed at the beginning of discharge. Further lithiation induces the formation of a-Liₓ(Si/Ge) intermediates and the crystallization of Li₁₅(Si₀.₅Ge₀.₅)₄ at the end of the discharge. At really low voltages a reversible process of overlithiation and formation of Li₁₅₊δ(Si₀.₅Ge₀.₅)₄ was identified and related with a structural evolution of Li₁₅(Si₀.₅Ge₀.₅)₄. Upon charge, the c-Li₁₅(Si₀.₅Ge₀.₅)₄ was transformed into a-Liₓ(Si/Ge) intermediates. At the end of the process an amorphous phase assigned to a-SiₓGey was recovered. Thereby, it was demonstrated that Si and Ge are collectively active along the cycling process, upon discharge with the formation of a ternary Li₁₅(Si₀.₅Ge₀.₅)₄ phase (with a step of overlithiation) and upon charge with the rebuilding of the a-Si-Ge phase. This process is undoubtedly behind the enhanced performance of Si₀.₅Ge₀.₅ compared to a physical mixture of Si and Ge.

Keywords: lithium ion battery, silicon germanium anode, in situ characterization, X-Ray diffraction

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Hamadi Cherif, Christophe Coquelet, Paolo Stringari, Denis Clodic, Laura Pellegrini, Stefania Moioli, Stefano Langè

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Biogas is a promising technology which can be used as a vehicle fuel, for heat and electricity production, or injected in the national gas grid. It is storable, transportable, not intermittent and substitutable for fossil fuels. This gas produced from the wastewater treatment by degradation of organic matter under anaerobic conditions is mainly composed of methane and carbon dioxide. To be used as a renewable fuel, biogas, whose energy comes only from methane, must be purified from carbon dioxide and other impurities such as water vapor, siloxanes and hydrogen sulfide. Purification of biogas for this application particularly requires the removal of hydrogen sulfide, which negatively affects the operation and viability of equipment especially pumps, heat exchangers and pipes, causing their corrosion. Several methods are available to eliminate hydrogen sulfide from biogas. Herein, reactive absorption in structured packed column by means of chemical absorption in aqueous sodium hydroxide solutions is considered. This study is based on simulations using Aspen Plus™ V8.0, and comparisons are done with data from an industrial pilot plant treating 85 Nm3/h of biogas which contains about 30 ppm of hydrogen sulfide. The rate-based model approach has been used for simulations in order to determine the efficiencies of separation for different operating conditions. To describe vapor-liquid equilibrium, a γ/ϕ approach has been considered: the Electrolyte NRTL model has been adopted to represent non-idealities in the liquid phase, while the Redlich-Kwong equation of state has been used for the vapor phase. In order to validate the thermodynamic model, Henry’s law constants of each compound in water have been verified against experimental data. Default values available in Aspen Plus™ V8.0 for the properties of pure components properties as heat capacity, density, viscosity and surface tension have also been verified. The obtained results for physical and chemical properties are in a good agreement with experimental data. Reactions involved in the process have been studied rigorously. Equilibrium constants for equilibrium reactions and the reaction rate constant for the kinetically controlled reaction between carbon dioxide and the hydroxide ion have been checked. Results of simulations of the pilot plant purification section show the influence of low temperatures, concentration of sodium hydroxide and hydrodynamic parameters on the selective absorption of hydrogen sulfide. These results show an acceptable degree of accuracy when compared with the experimental data obtained from the pilot plant. Results show also the great efficiency of sodium hydroxide for the removal of hydrogen sulfide. The content of this compound in the gas leaving the column is under 1 ppm.

Keywords: biogas, hydrogen sulfide, reactive absorption, sodium hydroxide, structured packed column

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Authors: Sudikshya Bhandari, Jonathan K. London

Abstract:

The earthquake of April 2015 was one of the biggest disasters in the history of Nepal. The epicenter was located near Barpak, north of the Gorkha district. Before the disaster, this settlement was a compact and homogeneous settlement manifesting its uniqueness through the social and cultural activities, and a distinct vernacular architecture. Narrow alleys with stone paved streets, buildings with slate roofs, and common spaces between the houses made this settlement socially, culturally, and environmentally cohesive. With the presence of micro hydro power plants, local economic activities enabled the local community to exist and thrive. Agriculture and animal rearing are the sources of livelihood for the majority of families, along with the booming homestays (where local people welcome guests to their home, as a business) and local shops. Most of these activities are difficult to find as the houses have been destroyed with the earthquake and the process of reconstruction has been transforming the outlook of the settlement. This study characterized the drastic transformation in Barpak post-earthquake, and analyzed the consequences of the reconstruction process. In addition, it contributes to comprehending a broader representation about unsustainability created by the lack of contextual post-disaster development. Since the research is based in a specific area, a case study approach was used. Sample houses were selected on the basis of ethnicity and house typology. Mixed methods such as key informant and semi structured interviews, focus groups, observations and photographs are used for the collection of data. The research focus is predominantly on the physical change of the house typology from vernacular to externally adopted designs. This transformation of the house entails socio-cultural changes such as social fragmentation with differences among the rich and the poor and decreases in the social connectivity within families and neighborhood. Families have found that new houses require more maintenance and resources that have increased their economic expenses. The study also found that the reconstructed houses are not thermally comfortable in the cold climate of Barpak, leading to the increased use of different sources of heating like electric heaters and more firewood. Lack of storage spaces for crops and livestock have discouraged them to pursue traditional means of livelihood and depend more on buying food from stores, ultimately making it less economical for most of the families. The transformation of space leading to the economic, social and cultural changes demonstrates the unsustainability of Barpak. Conclusions from the study suggest place based and inclusive planning and policy formations that include locals as partners, identifying the possible ways to minimize the impact and implement these recommendations into the future policy and planning scenarios.

Keywords: earthquake, Nepal, reconstruction, settlement, transformation

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Authors: Marie Guittonny-LarchevêQue

Abstract:

In boreal Canada, industrial activities such as forestry, peat extraction and metal mines often occur nearby. At closure, mine waste storage facilities have to be reclaimed. On tailings storage facilities, tree plantations can achieve rapid restoration of forested landscapes. However, trees poorly grow in mine tailings and organic amendments like peat are required to improve tailings’ structure and nutrients. Canada is a well-known producer of horticultural quality peat, but some lower quality peats coming from areas adjacent to the reclaimed mines could allow successful revegetation. In particular, hemic peat coming from the bottom of peat-bogs is more decomposed than fibric peat and is less valued for horticulture. Moreover, forest peat is sometimes excavated and piled by the forest industry after cuttings to stimulate tree regeneration on the exposed mineral soil. The objective of this project was to compare the ability of peats of differing quality and origin to improve tailings structure, nutrients and tree development. A greenhouse experiment was conducted along one growing season in 2016 with a complete randomized block design combining 8 repetitions (blocks) x 2 tree species (Populus tremuloides and Pinus banksiana) x 6 substrates (tailings, commercial horticultural peat, and mixtures of tailings with commercial peat, forest peat, local fibric peat, or local hemic peat) x 2 fertilization levels (with or without mineral fertilization). The used tailings came from a gold mine and were low in sulfur and trace metals. The commercial peat had a slightly acidic pH (around 6) while other peats had a clearly acidic pH (around 3). However, mixing peat with slightly alkaline tailings resulted in a pH close to 7 whatever the tested peats. The macroporosity of mixtures was intermediate between the low values of tailings (4%) and the high values of commercial peat alone (34%). Seedling survival was lower on tailings for poplar compared to all other treatments, with or without fertilization. Survival and growth were similar among all treatments for pine. Fertilization had no impact on the maximal height and diameter of poplar seedlings but changed the relative performance of the substrates. When not fertilized, poplar seedlings grown in commercial peat were the highest and largest, and the smallest and slenderest in tailings, with intermediate values in mixtures. When fertilized, poplar seedlings grown in commercial peat were smaller and slender compared to all other substrates. However for this species, foliar, shoot, and root biomass production was the greatest in commercial peat and the lowest in tailings compared to all mixtures, whether fertilized or not. The mixture with local fibric peat provided the seedlings with the lowest foliar N concentrations compared to all other substrates whatever the species or the fertilization treatment. At the short-term, the performance of all the tested peats were close when mixed to tailings, showing that peats of lower quality could be valorized instead of using horticultural peat. These results demonstrate that intersectorial synergies in accordance with the principles of circular economy may be developed in boreal Canada between local industries around the reclamation of mine waste dumps.

Keywords: boreal trees, mine spoil, mine revegetation, intersectorial synergies

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Authors: Hisham Arab Alkabeya, A. M. Hughes, J. Adams

Abstract:

Background: People with Rheumatoid Arthritis (RA) continue to experience problems with hand function despite new drug advances and targeted medical treatment. Consequently, it is important to identify the factors that influence the impact of RA disease on hand function. This systematic review identified observational studies that reported factors that influenced the impact of RA on hand function. Methods: MEDLINE, EMBASE, CINAL, AMED, PsychINFO, and Web of Science database were searched from January 1990 up to March 2017. Full-text articles published in English that described factors related to hand functional disability in people with RA were selected following predetermined inclusion and exclusion criteria. Pertinent data were thoroughly extracted and documented using a pre-designed data extraction form by the lead author, and cross-checked by the review team for completion and accuracy. Factors related to hand function were classified under the domains of the International Classification of Functioning, Disability, and Health (ICF) framework and health-related factors. Three reviewers independently assessed the methodological quality of the included articles using the quality of cross-sectional studies (AXIS) tool. Factors related to hand function that was investigated in two or more studies were explored using a best-evidence synthesis. Results: Twenty articles form 19 studies met the inclusion criteria from 1,271 citations; all presented cross-sectional data (five high quality and 15 low quality studies), resulting in at best limited evidence in the best-evidence synthesis. For the factors classified under the ICF domains, the best-evidence synthesis indicates that there was a range of body structure and function factors that were related with hand functional disability. However, key factors were hand strength, disease activity, and pain intensity. Low functional status (physical, emotional and social) level was found to be related with limited hand function. For personal factors, there is limited evidence that gender is not related with hand function; whereas, conflicting evidence was found regarding the relationship between age and hand function. In the domain of environmental factors, there was limited evidence that work activity was not related with hand function. Regarding health-related factors, there was limited evidence that the level of the rheumatoid factor (RF) was not related to hand function. Finally, conflicting evidence was found regarding the relationship between hand function and disease duration and general health status. Conclusion: Studies focused on body structure and function factors, highlighting a lack of investigation into personal and environmental factors when considering the impact of RA on hand function. The level of evidence which exists was limited, but identified that modifiable factors such as grip or pinch strength, disease activity and pain are the most influential factors on hand function in people with RA. The review findings suggest that important personal and environmental factors that impact on hand function in people with RA are not yet considered or reported in clinical research. Well-designed longitudinal, preferably cohort, studies are now needed to better understand the causality between personal and environmental factors and hand functional disability in people with RA.

Keywords: factors, hand function, rheumatoid arthritis, systematic review

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Authors: Andrew Cummings, Rhianne Boag, Sarah Bryson, Gordon Turner

Abstract:

Packages designed for transport of radioactive material must satisfy rigorous safety regulations specified by the International Atomic Energy Agency (IAEA). Higher Activity Waste (HAW) transport packages have to maintain containment of their contents during normal and accident conditions of transport (NCT and ACT). To ensure containment criteria is satisfied these packages are required to be leak-tight in all transport conditions to meet allowable activity release rates. Package design safety reports are the safety cases that provide the claims, evidence and arguments to demonstrate that packages meet the regulations and once approved by the competent authority (in the UK this is the Office for Nuclear Regulation) a licence to transport radioactive material is issued for the package(s). The standard approach to demonstrating containment in the RWM transport safety case is set out in BS EN ISO 12807. In this document a method for measuring a leak rate from the package is explained by way of a small interspace test volume situated between two O-ring seals on the underside of the package lid. The interspace volume is pressurised and a pressure drop measured. A small interspace test volume makes the method more sensitive enabling the measurement of smaller leak rates. By ascertaining the activity of the contents, identifying a releasable fraction of material and by treating that fraction of material as a gas, allowable leak rates for NCT and ACT are calculated. The adherence to basic safety principles in ISO12807 is very pessimistic and current practice in the demonstration of transport safety, which is accepted by the UK regulator. It is UK government policy that management of HAW will be through geological disposal. It is proposed that the intermediate level waste be transported to the geological disposal facility (GDF) in large cuboid packages. This poses a challenge for containment demonstration because such packages will have long seals and therefore large interspace test volumes. There is also uncertainty on the releasable fraction of material within the package ullage space. This is because the waste may be in many different forms which makes it difficult to define the fraction of material released by the waste package. Additionally because of the large interspace test volume, measuring the calculated leak rates may not be achievable. For this reason a justification for a lower releasable fraction of material is sought. This paper considers the use of aerosol processes to reduce the releasable fraction for both NCT and ACT. It reviews the basic coagulation and removal processes and applies the dynamic aerosol balance equation. The proposed solution includes only the most well understood physical processes namely; Brownian coagulation and gravitational settling. Other processes have been eliminated either on the basis that they would serve to reduce the release to the environment further (pessimistically in keeping with the essence of nuclear transport safety cases) or that they are not credible in the conditions of transport considered.

Keywords: aerosol processes, Brownian coagulation, gravitational settling, transport regulations

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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