Search results for: India's traditional knowledge digital library

Authors: Mohammad Al-Refai, Majed Wakid

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Introduction: Soil-transmitted diseases (STD) are caused by intestinal worms that are transmitted via various routes into the human body resulting in various clinical manifestations. The intestinal worms causing these infections are known as soil transmitted helminths (STH), including Hook worms, Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), and Strongyloides sterocoralis (S. sterocoralis). Objectives: The aim of this study was to investigate the prevalence of STH among newly arrived expatriate labors in Jeddah city, Saudi Arabia, using three different techniques (direct smears, sedimentation concentration, and real-time PCR). Methods: A total of 188 stool specimens were collected and investigated at the parasitology laboratory in the Special Infectious Agents Unit at King Fahd Medical Research Center, King Abdulaziz University in Jeddah, Saudi Arabia. Microscopic examination of wet mount preparations using normal saline and Lugols Iodine was carried out, followed by the formal ether sedimentation method. In addition, real-time PCR was used as a molecular tool to detect several STH and hookworm speciation. Results: Out of 188 stool specimens analyzed, in addition to STH parasite, several other types were detected. 9 samples (4.79%) were positive for Entamoeba coli, 7 samples (3.72%) for T. trichiura, 6 samples (3.19%) for Necator americanus, 4 samples (2.13%) for S. sterocoralis, 4 samples (2.13%) for A. lumbricoides, 4 samples (2.13%) for E. histolytica, 3 samples (1.60%) for Blastocystis hominis, 2 samples (1.06%) for Ancylostoma duodenale, 2 samples (1.06%) for Giardia lamblia, 1 sample (0.53%) for Iodamoeba buetschlii, 1 sample (0.53%) for Hymenolepis nana, 1 sample (0.53%) for Endolimax nana, and 1 sample (0.53%) for Heterophyes heterophyes. Out of the 35 infected cases, 26 revealed single infection, 8 with double infections, and only one triple infection of different STH species and other intestinal parasites. Higher rates of STH infections were detected among housemaids (11 cases) followed by drivers (7 cases) when compared to other occupations. According to educational level, illiterate participants represent the majority of infected workers (12 cases). The majority of workers' positive cases were from the Philippines. In comparison between laboratory techniques, out of the 188 samples screened for STH, real-time PCR was able to detect the DNA in (19/188) samples followed by Ritchie sedimentation technique (18/188), and direct wet smear (7/188). Conclusion: STH infections are a major public health issue to healthcare systems around the world. Communities must be educated on hygiene practices and the severity of such parasites to human health. As far as drivers and housemaids come to close contact with families, including children and elderlies. This may put family members at risk of developing serious side effects related to STH, especially as the majority of workers were illiterate, lacking the basic hygiene knowledge and practices. We recommend the official authority in Jeddah and around the kingdom of Saudi Arabia to revise the standard screening tests for newly arrived workers and enforce regular follow-up inspections to minimize the chances of the spread of STH from expatriate workers to the public.

Keywords: expatriate labors, Jeddah, prevalence, soil transmitted helminths

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Authors: Catherine Alex Agbor

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The modern Nigerian society is dynamic, divided in zones based on economic, political and educational resources often shared across the zones. The Six Geopolitical Zones in Nigeria is a major division in modern Nigeria, created during the regime of president Ibrahim Badamasi Babangida. They are North Central, North East, North West, South East, South South and South West. However, the zone used in this study is known as former South-Eastern State of Akwa-Ibom State and Cross-River State; former Rivers State of Bayelsa State and Rivers State; and former Mid-Western Region, Nigeria of Delta State and Edo State. Many reforms have taken place overtime, particularly in the education sector. Education is constantly presenting new ideas and innovative approaches which act to facilitate the rapid exchange of knowledge and provide quality basic education for learners. The Federal Government of Nigeria in accordance with its National Council on Education directed the Nigerian Educational Research and Development Council to restructure its basic education curriculum with the hope to enable the nation meet national and global developmental goals. One of the goals of the 9-year Basic Education Programme is developing in the entire citizenry a strong consciousness for education and a strong commitment to its vigorous promotion. Another is ensuring the acquisition of appropriate levels of literacy, numeracy, manipulative, communicative and life-skills as well as the ethical, moral and civic values for laying a solid foundation for lifelong learning. Therefore, this article at the introductory stage is aimed to describe some key issues in Nigeria’s experience in the basic education curriculum. In this study, particular attention is paid to this very recent educational policy of the Nigerian government known as Universal Basic Education, its challenges and what can be done to make the policy achieve its desired objectives. It progresses to analyze modern requirements for second language teaching; and presents the challenges of second language teaching in Nigeria. Finally, it reports a study which investigated special efforts for appropriate achievement of quality education in language classroom in the south-south zone of Nigeria. One fundamental research question was posed on what educational practices can contribute to current understanding of the structure of language curriculum. More explicitly, the study was designed to analyze the extent to which quality content contributes to current understanding of the structure of school curriculum in the zone. Otherwise stated, it investigated how student-centred educational practices impact on their learning of French language. One hundred and eighty (180) participants (teachers) were purposefully sampled for the study. Qualitative technique was used to elicit information from participants. The qualitative method used was Focus Group Discussion (FGD). Participants were divided into six groups comprising of 30 teachers from each zone. Group discussions were based mainly on curriculum contents and practices. Information from participants revealed that the curriculum content, among others is inadequate and should be re-examined. Recommendations were proffered as a panacea to concrete implementation of the basic education in Nigeria.

Keywords: basic education, quality contents, second language, south-south states

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Authors: X. Simon, D. Copena, M. Montero

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The last decades have witnessed a significant increase in renewable energy, especially wind energy, to achieve sustainable development. Specialized literature in this field has carried out interesting case studies to extensively analyze both the environmental benefits of this energy and its social acceptance. However, to the best of our knowledge, work to date makes no analysis of the role of private owners of lands with wind potential within a broader territory of strong wind implantation, nor does it estimate their economic incomes relating them to social acceptance. This work fills this gap by focusing on Galicia, territory housing over 4,000 wind turbines and almost 3,400 MW of power. The main difficulty in getting this financial information is that it is classified, not public. We develop methodological techniques (semi- structured interviews and work groups), inserted within the Participatory Research, to overcome this important obstacle. In this manner, the work directly compiles qualitative and quantitative information on the processes as well as the economic results derived from implementing wind energy in Galicia. During the field work, we held 106 semi-structured interviews and 32 workshops with owners of lands occupied by wind farms. The compiled information made it possible to create the socioeconomic database on wind energy in Galicia (SDWEG). This database collects a diversity of quantitative and qualitative information and contains economic information on the income received by the owners of lands occupied by wind farms. In the Galician case, regulatory framework prevented local participation under the community wind farm formula. The possibility of local participation in the new energy model narrowed down to companies wanting to install a wind farm and demanding land occupation. The economic mechanism of local participation begins here, thus explaining the level of acceptance of wind farms. Land owners can receive significant income given that these payments constitute an important source of economic resources, favor local economic activity, allow rural areas to develop productive dynamism projects and improve the standard of living of rural inhabitants. This work estimates that land owners in Galicia perceive about 10 million euros per year in total wind revenues. This represents between 1% and 2% of total wind farm invoicing. On the other hand, relative revenues (Euros per MW), far from the amounts reached in other spaces, show enormous payment variability. This signals the absence of a regulated market, the predominance of partial agreements, and the existence of asymmetric positions between owners and developers. Sustainable development requires the replacement of conventional technologies by low environmental impact technologies, especially those that emit less CO₂. However, this new paradigm also requires rural owners to participate in the income derived from the structural transformation processes linked to sustainable development. This paper demonstrates that regulatory framework may contribute to increasing sustainable technologies with high social acceptance without relevant local economic participation.

Keywords: regulatory framework, social acceptance, sustainable development, wind energy, wind income for landowners

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Authors: Rosa Nadine Danenberg

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In recent years, bottom-up urban development has started growing as an alternative to conventional top-down planning. In large proportions, citizens and communities initiate small-scale interventions; suddenly seeming to form a trend. As a result, more and more cities are witnessing not only the growth of but also an interest in these initiatives, as they bear the potential to reshape urban spaces. Such alternative city-making efforts cause new dynamics in urban governance, with inevitable consequences for the controlled city planning and its administration. The emergence of enabling relationships between top-down and bottom-up actors signals an increasingly common urban practice. Various case studies show that an enabling relationship is possible, yet, how it can be optimally realized stays rather underexamined. Therefore, the seemingly growing worldwide phenomenon of ‘municipal bottom-up urban development’ necessitates an adequate governance structure. As such, the aim of this research is to contribute knowledge to how municipalities can enable citizen-led urban initiatives from a governance innovation perspective. Empirical case-study research in Stockholm and Istanbul, derived from interviews with founders of four citizen-led urban initiatives and one municipal representative in each city, provided valuable insights to possibilities and constraints for enabling practices. On the one hand, diverging outcomes emphasize the extreme oppositional features of both cases (Stockholm and Istanbul). Firstly, both cities’ characteristics are drastically different. Secondly, the ideologies and motifs for the initiatives to emerge vary widely. Thirdly, the major constraints for citizen-led urban initiatives to relate to the municipality are considerably different. Two types of municipality’s organizational structures produce different underlying mechanisms which demonstrate the constraints. The first municipal organizational structure is steered by bureaucracy (Stockholm). It produces an administrative division that brings up constraints such as the lack of responsibility, transparency and continuity by municipal representatives. The second structure is dominated by municipal politics and governmental hierarchy (Istanbul). It produces informality, lack of transparency and a fragmented civil society. In order to cope with the constraints produced by both types of organizational structures, the initiatives have adjusted their organization to the municipality’s underlying structures. On the other hand, this paper has in fact also come to a rather unifying conclusion. Interestingly, the suggested possibilities for an enabling relationship underline converging new urban governance arrangements. This could imply that for the two varying types of municipality’s organizational structures there is an accurate governance structure. Namely, the combination of a neighborhood council with a municipal guide, with allowance for the initiatives to adopt a politicizing attitude is found as coinciding. Especially its combination appears key to redeem varying constraints. A municipal guide steers the initiatives through bureaucratic struggles, is supported by coproduction methods, while it balances out municipal politics. Next, a neighborhood council, that is politically neutral and run by local citizens, can function as an umbrella for citizen-led urban initiatives. What is crucial is that it should cater for a more entangled relationship between municipalities and initiatives with enhanced involvement of the initiatives in decision-making processes and limited involvement of prevailing constraints pointed out in this research.

Keywords: bottom-up urban development, governance innovation, Istanbul, Stockholm

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Authors: S. Toufigh Bararpour, Davood Karami, Nader Mahinpey

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Dependence of global economics on fossil fuels has led to a large growth in the emission of greenhouse gases (GHGs). Among the various GHGs, carbon dioxide is the main contributor to the greenhouse effect due to its huge emission amount. To mitigate the threatening effect of CO₂, carbon capture and sequestration (CCS) technologies have been studied widely in recent years. For the combustion processes, three main CO₂ capture techniques have been proposed such as post-combustion, pre-combustion and oxyfuel combustion. Post-combustion is the most commonly used CO₂ capture process as it can be readily retrofit into the existing power plants. Multiple advantages have been reported for the post-combustion by solid sorbents such as high CO₂ selectivity, high adsorption capacity, and low required regeneration energy. Chemical adsorption of CO₂ over alkali-metal-based solid sorbents such as K₂CO₃ is a promising method for the selective capture of diluted CO₂ from the huge amount of nitrogen existing in the flue gas. To improve the CO₂ capture performance, K₂CO₃ is supported by a stable and porous material. Al₂O₃ has been employed commonly as the support and enhanced the cyclic CO₂ capture efficiency of K₂CO₃. Different phases of alumina can be obtained by setting the calcination temperature of boehmite at 300, 600 (γ-alumina), 950 (δ-alumina) and 1200 °C (α-alumina). By increasing the calcination temperature, the regeneration capacity of alumina increases, while the surface area reduces. However, sorbents with lower surface areas have lower CO₂ capture capacity as well (except for the sorbents prepared by hydrophilic support materials). To resolve this issue, a highly efficient alumina-aerogel support was synthesized with a BET surface area of over 2000 m²/g and then calcined at a high temperature. The synthesized alumina-aerogel was impregnated on K₂CO₃ based on 50 wt% support/K₂CO₃, which resulted in the preparation of a sorbent with remarkable CO₂ capture performance. The effect of synthesis conditions such as types of alcohols, solvent-to-co-solvent ratios, and aging times was investigated on the performance of the support. The best support was synthesized using methanol as the solvent, after five days of aging time, and at a solvent-to-co-solvent (methanol-to-toluene) ratio (v/v) of 1/5. Response surface methodology was used to investigate the effect of operating parameters such as carbonation temperature and H₂O-to-CO₂ flowrate ratio on the CO₂ capture capacity. The maximum CO₂ capture capacity, at the optimum amounts of operating parameters, was 7.2 mmol CO₂ per gram K₂CO₃. Cyclic behavior of the sorbent was examined over 20 carbonation and regenerations cycles. The alumina-aerogel-supported K₂CO₃ showed a great performance compared to unsupported K₂CO₃ and γ-alumina-supported K₂CO₃. Fundamental performance analyses and long-term thermal and chemical stability test will be performed on the sorbent in the future. The applicability of the sorbent for a bench-scale process will be evaluated, and a corresponding process model will be established. The fundamental material knowledge and respective process development will be delivered to industrial partners for the design of a pilot-scale testing unit, thereby facilitating the industrial application of alumina-aerogel.

Keywords: alumina-aerogel, CO₂ capture, K₂CO₃, optimization

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Authors: C. Fernandez-Plaza, I. Abad, E. Diaz, I. Diaz

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Births occurring before the 37th week of gestation are considered preterm births. A threat of preterm is defined as the beginning of regular uterine contractions, dilation and cervical effacement between 23 and 36 gestation weeks. To author's best knowledge, the factors that determine the beginning of the birth are not completely defined yet. In particular, the incidence of sleep habits on preterm births is weekly studied. The aim of this study is to develop a model to predict the factors affecting premature delivery on pregnancy, based on the above potential risk factors, including those derived from sleep habits and light exposure at night (introduced as 12 variables obtained by a telephone survey using two questionnaires previously used by other authors). Thus, three groups of variables were included in the study (maternal, fetal and sleep habits). The study was approved by Research Ethics Committee of the Principado of Asturias (Spain). An observational, retrospective and descriptive study was performed with 481 births between January 1, 2015 and May 10, 2016 in the University Central Hospital of Asturias (Spain). A statistical analysis using SPSS was carried out to compare qualitative and quantitative variables between preterm and term delivery. Chi-square test qualitative variable and t-test for quantitative variables were applied. Statistically significant differences (p < 0.05) between preterm vs. term births were found for primiparity, multi-parity, kind of conception, place of residence or premature rupture of membranes and interruption during nights. In addition to the statistical analysis, machine learning methods to look for a prediction model were tested. In particular, tree based models were applied as the trade-off between performance and interpretability is especially suitable for this study. C5.0, recursive partitioning, random forest and tree bag models were analysed using caret R-package. Cross validation with 10-folds and parameter tuning to optimize the methods were applied. In addition, different noise reduction methods were applied to the initial data using NoiseFiltersR package. The best performance was obtained by C5.0 method with Accuracy 0.91, Sensitivity 0.93, Specificity 0.89 and Precision 0.91. Some well known preterm birth factors were identified: Cervix Dilation, maternal BMI, Premature rupture of membranes or nuchal translucency analysis in the first trimester. The model also identifies other new factors related to sleep habits such as light through window, bedtime on working days, usage of electronic devices before sleeping from Mondays to Fridays or change of sleeping habits reflected in the number of hours, in the depth of sleep or in the lighting of the room. IF dilation < = 2.95 AND usage of electronic devices before sleeping from Mondays to Friday = YES and change of sleeping habits = YES, then preterm is one of the predicting rules obtained by C5.0. In this work a model for predicting preterm births is developed. It is based on machine learning together with noise reduction techniques. The method maximizing the performance is the one selected. This model shows the influence of variables related to sleep habits in preterm prediction.

Keywords: machine learning, noise reduction, preterm birth, sleep habit

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Authors: Tomasz Balabanski, Anna Biedunkiewicz

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Research on basic bacteriological and physicochemical parameters conducted by state institutions (Provincial Sanitary and Epidemiological Station and District Sanitary and Epidemiological Station) are limited to bathing waters under constant sanitary and epidemiological supervision. Unfortunately, no routine or monitoring tests are carried out for the presence of microfungi. This also applies to beach sand used for recreational purposes. The purpose of the planned own research was to determine the diversity of the mycobiota present on supervised and unsupervised sandy beaches, on the shores of lakes, of municipal baths used for recreation. The research material consisted of microfungi isolated from April to October 2019 from sandy beaches of supervised and unsupervised lakes located within the administrative boundaries of the city of Olsztyn (North-Eastern Poland, Europe). Four lakes, out of the fifteen available (Tyrsko, Kortowskie, Skanda, and Ukiel), whose bathing waters are subjected to routine bacteriological tests, were selected for testing. To compare the diversity of the mycobiota composition on the surface and below the sand mixing layer, samples were taken from two depths (10 cm and 50 cm), using a soil auger. Micro-fungi from sand samples were obtained by surface inoculation on an RBC medium from the 1st dilution (1:10). After incubation at 25°C for 96-144 h, the average number of CFU/dm³ was counted. Morphologically differing yeast colonies were passaged into Sabouraud agar slants with gentamicin and incubated again. For detailed laboratory analyses, culture methods (macro- and micro-cultures) and identification methods recommended in diagnostic mycological laboratories were used. The conducted research allowed obtaining 140 yeast isolates. The total average population ranged from 1.37 × 10⁻² CFU/dm³ before the bathing season (April 2019), 1.64 × 10⁻³ CFU/dm³ in the season (May-September 2019), and 1.60 × 10⁻² CFU/dm³ after the end of the season (October 2019). More microfungi were obtained from the surface layer of sand (100 isolates) than from the deeper layer (40 isolates). Reported microfungi may circulate seasonally between individual elements of the lake ecosystem. From the sand/soil from the catchment area beaches, they can get into bathing waters, stopping periodically on the coastal phyllosphere. The sand of the beaches and the phyllosphere are a kind of filter for the water reservoir. The presence of microfungi with various pathogenicity potential in these places is of major epidemiological importance. Therefore, full monitoring of not only recreational waters but also sandy beaches should be treated as an element of constant control by appropriate supervisory institutions, allowing recreational areas for public use so that the use of these places does not involve the risk of infection. Acknowledgment: 'Development Program of the University of Warmia and Mazury in Olsztyn', POWR.03.05.00-00-Z310/17, co-financed by the European Union under the European Social Fund from the Operational Program Knowledge Education Development. Tomasz Bałabański is a recipient of a scholarship from the Programme Interdisciplinary Doctoral Studies in Biology and Biotechnology (POWR.03.05.00-00-Z310/17), which is funded by the 'European Social Fund'.

Keywords: beach, microfungi, sand, yeasts

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Authors: Leonie Bradfield, Stephen Fityus, John Simmons

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The shearing behavior of current and planned coal mine spoil dumps up to 400m in height is studied using large-sample-high-stress direct shear tests performed on a range of spoils common to the coalfields of Eastern Australia. The motivation for the study is to address industry concerns that some constructed spoil dump heights ( > 350m) are exceeding the scale ( ≤ 120m) for which reliable design information exists, and because modern geotechnical laboratories are not equipped to test representative spoil specimens at field-scale stresses. For more than two decades, shear strength estimation for spoil dumps has been based on either infrequent, very small-scale tests where oversize particles are scalped to comply with device specimen size capacity such that the influence of prototype-sized particles on shear strength is not captured; or on published guidelines that provide linear shear strength envelopes derived from small-scale test data and verified in practice by slope performance of dumps up to 120m in height. To date, these published guidelines appear to have been reliable. However, in the field of rockfill dam design there is a broad acceptance of a curvilinear shear strength envelope, and if this is applicable to coal mine spoils, then these industry-accepted guidelines may overestimate the strength and stability of dumps at higher stress levels. The pressing need to rationally define the shearing behavior of more representative spoil specimens at field-scale stresses led to the successful design, construction and operation of a large direct shear machine (LDSM) and its subsequent application to provide reliable design information for current and planned very-high dumps. The LDSM can test at a much larger scale, in terms of combined specimen size (720mm x 720mm x 600mm) and stress (σn up to 4.6MPa), than has ever previously been achieved using a direct shear machine for geotechnical testing of rockfill. The results of an extensive LDSM testing program on a wide range of coal-mine spoils are compared to a published framework that widely accepted by the Australian coal mining industry as the standard for shear strength characterization of mine spoil. A critical outcome is that the LDSM data highlights several non-compliant spoils, and stress-dependent shearing behavior, for which the correct application of the published framework will not provide reliable shear strength parameters for design. Shear strength envelopes developed from the LDSM data are also compared with dam engineering knowledge, where failure envelopes of rockfills are curved in a concave-down manner. The LDSM data indicates that shear strength envelopes for coal-mine spoils abundant with rock fragments are not in fact curved and that the shape of the failure envelope is ultimately determined by the strength of rock fragments. Curvilinear failure envelopes were found to be appropriate for soil-like spoils containing minor or no rock fragments, or hard-soil aggregates.

Keywords: coal mine, direct shear test, high dump, large scale, mine spoil, shear strength, spoil dump

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Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

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Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

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Authors: Vijaya Dixit Aasheesh Dixit

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Shipbuilding industry operates in Engineer Procure Construct (EPC) context. Product mix of a shipyard comprises of various types of ships like bulk carriers, tankers, barges, coast guard vessels, sub-marines etc. Each order is unique based on the type of ship and customized requirements, which are engineered into the product right from design stage. Thus, to execute every new project, a shipyard needs to upgrade its production expertise. As a result, over the long run, holistic learning occurs across different types of projects which contributes to the knowledge base of the shipyard. Simultaneously, in the short term, during execution of a project comprising of multiple sister ships, repetition of similar tasks leads to learning at activity level. This research aims to capture above learnings of a shipyard and incorporate learning curve effect in project scheduling and materials procurement to improve project performance. Extant literature provides support for the existence of such learnings in an organization. In shipbuilding, there are sequences of similar activities which are expected to exhibit learning curve behavior. For example, the nearly identical structural sub-blocks which are successively fabricated, erected, and outfitted with piping and electrical systems. Learning curve representation can model not only a decrease in mean completion time of an activity, but also a decrease in uncertainty of activity duration. Sister ships have similar material requirements. The same supplier base supplies materials for all the sister ships within a project. On one hand, this provides an opportunity to reduce transportation cost by batching the order quantities of multiple ships. On the other hand, it increases the inventory holding cost at shipyard and the risk of obsolescence. Further, due to learning curve effect the production scheduled of each consequent ship gets compressed. Thus, the material requirement schedule of every next ship differs from its previous ship. As more and more ships get constructed, compressed production schedules increase the possibility of batching the orders of sister ships. This work aims at integrating materials management with project scheduling of long duration projects for manufacturing of multiple sister ships. It incorporates the learning curve effect on progressively compressing material requirement schedules and addresses the above trade-off of transportation cost and inventory holding and shortage costs while satisfying budget constraints of various stages of the project. The activity durations and lead time of items are not crisp and are available in the form of probabilistic distribution. A Stochastic Mixed Integer Programming (SMIP) model is formulated which is solved using evolutionary algorithm. Its output provides ordering dates of items and degree of order batching for all types of items. Sensitivity analysis determines the threshold number of sister ships required in a project to leverage the advantage of learning curve effect in materials management decisions. This analysis will help materials managers to gain insights about the scenarios: when and to what degree is it beneficial to treat a multiple ship project as an integrated one by batching the order quantities and when and to what degree to practice distinctive procurement for individual ship.

Keywords: learning curve, materials management, shipbuilding, sister ships

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Authors: Sara Saboonian, Pierre Filion

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The dispersed-suburban model has been the dominant one across North America for the past seventy years, characterized by automobile reliance, low density, and land-use specialization. Two planning models have emerged as possible alternatives to address the ills inflicted by this development pattern. First, there is intensification, which promotes efficient infrastructure by connecting high-density, multi-functional, and walkable nodes with public transit services within the suburban landscape. Second is green infrastructure, which provides environmental health and human well-being by preserving and restoring ecosystem services. This research studies incompatibilities and the possibility of amalgamating the two alternatives in an attempt to develop a comprehensive alternative to suburban model that advocates density, multi-functionality and transit- and pedestrian-conduciveness, with measures capable of mitigating the adverse environmental impacts of compactness. The research investigates three Canadian urban growth centers, where intensification is the current planning practice, and the awareness of green infrastructure benefits is on the rise. However, these three centers are contrasted by their development stage, the presence or absence of protected natural land, their environmental approach, and their adverse environmental consequences according to the planning cannons of different periods. The methods include reviewing the literature on green infrastructure planning, criticizing the Ontario provincial plans for intensification, surveying residents’ preferences for alternative models, and interviewing officials who deal with the local planning for the centers. Moreover, the research draws on recalling debates between New Urbanism and Landscape/Ecological Urbanism. The case studies expose the difficulties in creating urban growth centres that accommodate green infrastructure while adhering to intensification principles. First, the dominant status of intensification and the obstacles confronting intensification have monopolized the planners’ concerns. Second, the tension between green infrastructure and intensification explains the absence of the green infrastructure typologies that correspond to intensification-compatible forms and dynamics. Finally, the lack of highlighted social-economic benefits of green infrastructure reduces residents’ participation. Moreover, the results from the research provide insight into predominating urbanization theories, New Urbanism and Landscape/Ecological Urbanism. In order to understand political, planning, and ecological dynamics of such blending, dexterous context-specific planning is required. Findings suggest the influence of the following factors on amalgamating intensification and green infrastructure. Initially, producing ecosystem services-based justifications for green infrastructure development in the intensification context provides an expert-driven backbone for the implementation programs. This knowledge-base should be translated to effectively imbue different urban stakeholders. Moreover, due to the limited greenfields in intensified areas, spatial distribution and development of multi-level corridors such as pedestrian-hospitable settings and transportation networks along green infrastructure measures are required. Finally, to ensure the long-term integrity of implemented green infrastructure measures, significant investment in public engagement and education, as well as clarification of management responsibilities is essential.

Keywords: ecosystem services, green infrastructure, intensification, planning

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Authors: Thilina Ranaweera, Enes Makalic, John L. Hopper, Adrian Bickerstaffe

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Data are the primary asset of biomedical researchers, and the engine for both discovery and research translation. As the volume and complexity of research datasets increase, especially with new technologies such as large single nucleotide polymorphism (SNP) chips, so too does the requirement for software to manage, process and analyze the data. Researchers often need to execute complicated queries and conduct complex analyzes of large-scale datasets. Existing tools to analyze such data, and other types of high-dimensional data, unfortunately suffer from one or more major problems. They typically require a high level of computing expertise, are too simplistic (i.e., do not fit realistic models that allow for complex interactions), are limited by computing power, do not exploit the computing power of large-scale parallel architectures (e.g. supercomputers, GPU clusters etc.), or are limited in the types of analysis available, compounded by the fact that integrating new analysis methods is not straightforward. Solutions to these problems, such as those developed and implemented on parallel architectures, are currently available to only a relatively small portion of medical researchers with access and know-how. The past decade has seen a rapid expansion of data management systems for the medical domain. Much attention has been given to systems that manage phenotype datasets generated by medical studies. The introduction of heterogeneous genomic data for research subjects that reside in these systems has highlighted the need for substantial improvements in software architecture. To address this problem, we have developed SPARK, an enabling and translational system for medical research, leveraging existing high performance computing resources, and analysis techniques currently available or being developed. It builds these into The Ark, an open-source web-based system designed to manage medical data. SPARK provides a next-generation biomedical data management solution that is based upon a novel Micro-Service architecture and Big Data technologies. The system serves to demonstrate the applicability of Micro-Service architectures for the development of high performance computing applications. When applied to high-dimensional medical datasets such as genomic data, relational data management approaches with normalized data structures suffer from unfeasibly high execution times for basic operations such as insert (i.e. importing a GWAS dataset) and the queries that are typical of the genomics research domain. SPARK resolves these problems by incorporating non-relational NoSQL databases that have been driven by the emergence of Big Data. SPARK provides researchers across the world with user-friendly access to state-of-the-art data management and analysis tools while eliminating the need for high-level informatics and programming skills. The system will benefit health and medical research by eliminating the burden of large-scale data management, querying, cleaning, and analysis. SPARK represents a major advancement in genome research technologies, vastly reducing the burden of working with genomic datasets, and enabling cutting edge analysis approaches that have previously been out of reach for many medical researchers.

Keywords: biomedical research, genomics, information systems, software

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Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

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Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Ma Chu Jui

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Culture plays a pivotal role in shaping societal responses to change and fostering adaptability. In the realm of healthcare provision, hospitals serve as dynamic settings molded by the cultural consciousness of healthcare professionals. This intricate interplay extends to their expectations of leadership, communication styles, and attitudes towards patient care. Recognizing the cultural inclinations of healthcare professionals becomes imperative in navigating this complex landscape. This study will utilize Hofstede's Value Survey Module 2013 (VSM 2013) as a comprehensive analytical tool. The targeted participants for this research are in-service nursing professionals with a tenure of at least three months, specifically employed in the nursing department of an Eastern hospital. This quantitative approach seeks to quantify diverse cultural tendencies among the targeted nursing professionals, elucidating not only abstract cultural concepts but also revealing their cultural inclinations across different dimensions. The study anticipates gathering between 400 to 500 responses, ensuring a robust dataset for a comprehensive analysis. The focused approach on nursing professionals within the Eastern hospital setting enhances the relevance and specificity of the cultural insights obtained. The research aims to contribute valuable knowledge to the understanding of cultural tendencies among in-service nursing personnel in the nursing department of this specific Eastern hospital. The VSM 2013 will be initially distributed to this specific group to collect responses, aiming to calculate scores on each of Hofstede's six cultural dimensions—Power Distance Index (PDI), Individualism vs. Collectivism (IDV), Uncertainty Avoidance Index (UAI), Masculinity vs. Femininity (MAS), Long-Term Orientation vs. Short-Term Normative Orientation (LTO), and Indulgence vs. Restraint (IVR). the study unveils a significant correlation between different cultural dimensions and healthcare professionals' tendencies in understanding leadership expectations through PDI, grasping behavioral patterns via IDV, acknowledging risk acceptance through UAI, and understanding their long-term and short-term behaviors through LTO. These tendencies extend to communication styles and attitudes towards patient care. These findings provide valuable insights into the nuanced interconnections between cultural factors and healthcare practices. Through a detailed analysis of the varying levels of these cultural dimensions, we gain a comprehensive understanding of the predominant inclinations among the majority of healthcare professionals. This nuanced perspective adds depth to our comprehension of how cultural values shape their approach to leadership, communication, and patient care, contributing to a more holistic understanding of the healthcare landscape. A profound comprehension of the cultural paradigms embraced by healthcare professionals holds transformative potential. Beyond a mere understanding, it acts as a catalyst for elevating the caliber of healthcare services. This heightened awareness fosters cohesive collaboration among healthcare teams, paving the way for the establishment of a unified healthcare ethos. By cultivating shared values, our study envisions a healthcare environment characterized by enhanced quality, improved teamwork, and ultimately, a more favorable and patient-centric healthcare landscape. In essence, our research underscores the critical role of cultural awareness in shaping the future of healthcare delivery.

Keywords: hofstede's cultural, cultural dimensions, cultural values in healthcare, cultural awareness in nursing

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Authors: Rodriguez Diego, Del Valle Martin, Hargreaves Matias, Riveros Jose Luis

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Nutrient deficiencies due to a diet low in quantitative and qualitative terms, are prevalent throughout the developing world, especially in sub-Saharan Africa. Children and women of childbearing age are especially vulnerable. Limited availability, access and intake of animal foods at home and lack of knowledge about their value in the diet and the role they play in health, contribute to poor diet quality. Poor bioavailability of micronutrients in diets based on foods high in fiber and phytates, the low content of some micronutrients in these foods are further factors to consider. Goats are deeply embedded in almost every Sub-Saharan African rural culture, generally kept for their milk, meat, hair or leather. Goats have played an important role in African social life, especially in food security. Goat meat has good properties for human wellbeing, with a special role in lower income households. It has a high-quality protein (20 protein g/100 meat g) including all essential amino acids, good unsaturated/satured fatty acids relationship, and it is an important B-vitamin source with high micronutrients bioavailability. Mozambique has major food security problems, with poor food access and utilization, undiversified diets, chronic poverty and child malnutrition. Our objective was to design a nutritional intervention based on a dietary diversification, nutritional education, cultural beliefs and local resources, aimed to strengthen food security of children at Barrio Broma village (15°43'58.78"S; 32°46'7.27"E) in Chitima, Mozambique. Two surveys were conducted first of socio-productive local databases and then to 100 rural households about livelihoods, food diversity and anthropometric measurements in children under 5 years. Our results indicate that the main economic activity is goat production, based on a native breed with two deliveries per year in the absence of any management. Adult goats weighted 27.2±10.5 kg and raised a height of 63.5±3.8 cm. Data showed high levels of poverty, with a food diversity score of 2.3 (0-12 points), where only 30% of households consume protein and 13% iron, zinc, and B12 vitamin. The main constraints to food security were poor access to water and low income to buy food. Our dietary intervention was based on improving diet quality by increasing the access to dried goat meat, fresh vegetables, and legumes, and its utilization by a nutritional education program. This proposal was based on local culture and living conditions characterized by the absence of electricity power and drinkable water. The drying process proposed would secure the food maintenance under local conditions guaranteeing food safety for a longer period. Additionally, an ancient local drying technique was rescued and used. Moreover, this kind of dietary intervention would be the most efficient way to improve the infant nutrition by delivering macro and micronutrients on time to these vulnerable populations.

Keywords: child malnutrition, dietary diversification, food security, goat meat

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Authors: Peggy M. Randon, Lisa Randon

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Introduction: The post-COVID-19 era has presented unique challenges for addressing complex mental health issues, particularly due to exacerbated stress, increased social isolation, and disrupted continuity of care. This article outlines relevant health disparities and policy implications within the context of the United States while maintaining international relevance. Methods: A comprehensive literature review (including studies, reports, and policy documents) was conducted to examine concerns related to childhood-onset schizophrenia and the impact on patients and their families. Qualitative and quantitative data were synthesized to provide insights into the complex etiology of schizophrenia, the effects of the pandemic, and the challenges faced by socioeconomically disadvantaged populations. Case studies were employed to illustrate real-world examples and areas requiring policy reform. Results: Early intervention in childhood is crucial for preventing or mitigating the long-term impact of complex psychotic disorders, particularly schizophrenia. A comprehensive understanding of the genetic, environmental, and physiological factors contributing to the development of schizophrenia is essential. The COVID-19 pandemic worsened symptoms and disrupted treatment for many adolescent patients with schizophrenia, emphasizing the need for adaptive interventions and the utilization of virtual platforms. Health disparities, including stigma, financial constraints, and language or cultural barriers, further limit access to care, especially for socioeconomically disadvantaged populations. Policy implications: Current US health policies inadequately support patients with schizophrenia. The limited availability of longitudinal care, insufficient resources for families, and stigmatization represent ongoing policy challenges. Addressing these issues necessitates increased research funding, improved access to affordable treatment plans, and cultural competency training for healthcare providers. Public awareness campaigns are crucial to promote knowledge, awareness, and acceptance of mental health disorders. Conclusion: The unique challenges faced by children and families in the US affected by schizophrenia and other psychotic disorders have yet to be adequately addressed on institutional and systemic levels. The relevance of findings to an international audience is emphasized by examining the complex factors contributing to the onset of psychotic disorders and their global policy implications. The broad impact of the COVID-19 pandemic on mental health underscores the need for adaptive interventions and global responses. Addressing policy challenges, improving access to care, and reducing the stigma associated with mental health disorders are crucial steps toward enhancing the lives of adolescents and young adults with schizophrenia and their family members. The implementation of virtual platforms can help overcome barriers and ensure equitable access to support and resources for all patients, enabling them to lead healthy and fulfilling lives.

Keywords: childhood, schizophrenia, policy, United, States, health, disparities

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Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo N. Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

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Background: While delays to care exist in resource rich settings, greater delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of traumatic brain injury (TBI) in Sub Saharan Africa (SSA). While many LMICs have government subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold. First, due to a lack of a functional CT scanner at the tertiary hospital, patients need to arrange their own transportation to the nearby private facility for CT scans. Second, self-financing for the private CT scans ranges from $80 - $130, which is near the average monthly income in Kampala. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified ‘three delays’ framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Kristina F. Wolff

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Background: In the Federal Republic of Germany, violence against women is deeply embedded in society. Germany is, as of March 2020, the most populous member state of the European Union with 83.2 million inhabitants and, although more than half of its inhabitants are women, gender equality was not certified in the Basic Law until 1957. Women have only been allowed to enter paid employment without their husband's consent since 1977 and have marital rape prosecuted only since 1997. While the lack of equality between men and women is named in the preamble of the Istanbul Convention as the cause of gender-specific, structural, traditional violence against women, Germany continues to sink on the latest Gender Equality Index. According to Police Crime Statistics (PCS), women are significantly more often victims of lethal violence, emanating from men than vice versa. The PCS, which, since 2015, also collects gender-specific data on violent crimes, is kept by the Federal Criminal Police Office, but without taking into account the relevant criteria for targeted prevention, such as the history of violence of the perpetrator/killer, weapon, motivation, etc.. Institutions such as EIGE or the World Health Organization have been asking Germany for years in vain for comparable data on violence against women in order to gain an overview or to develop cross-border synergies. The PCS are the only official data collection on violence against women. All players involved are depend on this data set, which is published only in November of the following year and is thus already completely outdated at the time of publication. In order to combat German femicides causally, purposefully and efficiently, evidence-based data was urgently needed. Methodology: Beginning in January 2019, a database was set up that now tracks more than 600 German femicides, broken down by more than 100 crime-related individual criteria, which in turn go far beyond the official PCS. These data are evaluated on the one hand by daily media research, and on the other hand by case-specific inquiries at the respective public prosecutor's offices and courts nationwide. This quantitative long-term study covers domestic violence as well as a variety of different types of gender-specific, lethal violence, including, for example, femicides committed by German citizens abroad. Additionallyalcohol/ narcotic and/or drug abuse, infanticides and the gender aspect in the judiciary are also considered. Results: Since November 2020, evidence-based data from a scientific survey have been available for the first time in Germany, supplementing the rudimentary picture of reality provided by PCS with a number of relevant parameters. The most important goal of the study is to identify "red flags" that enable general preventive awareness, that serve increasingly precise hazard assessment in acute hazard situations, and from which concrete instructions for action can be identified. Already at a very early stage of the study it could be proven that in more than half of all femicides with a sexual perpetrator/victim constellation there was an age difference of five years or more. Summary: Without reliable data and an understanding of the nature and extent, cause and effect, it is impossible to sustainably curb violence against girls and women, which increasingly often culminates in femicide. In Germany, valid data from a scientific survey has been available for the first time since November 2020, supplementing the rudimentary reality picture of the official and, to date, sole crime statistics with several relevant parameters. The basic research provides insights into geo-concentration, monthly peaks and the modus operandi of male violent excesses. A significant increase of child homicides in the course of femicides and/or child homicides as an instrument of violence against the mother could be proven as well as a danger of affected persons due to an age difference of five years and more. In view of the steadily increasing wave of violence against women, these study results are an eminent contribution to the preventive containment of German femicides.

Keywords: femicide, violence against women, gender specific data, rule Of law, Istanbul convention, gender equality, gender based violence

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Authors: Jagmeet S. Kanwal, Julia F. Langley

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Music can heal the body, but a mechanistic understanding of this phenomenon is lacking. This study explores the effects of music presentation on neurologic and physiologic responses leading to metabolic changes in the human body. The mind and body co-exist in a corporeal entity and within this framework, sickness ensues when the mind-body balance goes awry. It is further hypothesized that music has the capacity to directly reset this balance. Two lines of inquiry taken together can provide a mechanistic understanding of this phenomenon 1) Empirical evidence for a sound-sensitive pressure sensor system in the body, and 2) The notion of a “healing center” within the brain that is activated by specific patterns of sounds. From an acoustics perspective, music is spatially distributed as pressure waves ranging from a few cm to several meters in wavelength. These waves interact and propagate in three-dimensions in unique ways, depending on the wavelength. Furthermore, music creates dynamically changing wave-fronts. Frequencies between 200 Hz and 1 kHz generate wavelengths that range from 5'6" to 1 foot. These dimensions are in the range of the body size of most people making it plausible that these pressure waves can geometrically interact with the body surface and create distinct patterns of pressure stimulation across the skin surface. For humans, short wavelength, high frequency (> 200 Hz) sounds are best received via cochlear receptors. For low frequency (< 200 Hz), long wavelength sound vibrations, however, the whole body may act as an ideal receiver. A vast array of highly sensitive pressure receptors (Pacinian corpuscles) is present just beneath the skin surface, as well as in the tendons, bones, several organs in the abdomen, and the sexual organs. Per the available empirical evidence, these receptors contribute to music perception by allowing the whole body to function as a sound receiver, and knowledge of how they function is essential to fully understanding the therapeutic effect of music. Neuroscientific studies have established that music stimulates the limbic system that can trigger states of anxiety, arousal, fear, and other emotions. These emotional states of brain activity play a crucial role in filtering top-down feedback from thoughts and bottom-up sensory inputs to the autonomic system, which automatically regulates bodily functions. Music likely exerts its pleasurable and healing effects by enhancing functional and effective connectivity and feedback mechanisms between brain regions that mediate reward, autonomic, and cognitive processing. Stimulation of pressure receptors under the skin by low-frequency music-induced sensations can activate multiple centers in the brain, including the amygdala, the cingulate cortex, and nucleus accumbens. Melodies in music in the low (< 600 Hz) frequency range may augment auditory inputs after convergence of the pressure-sensitive inputs from the vagus nerve onto emotive processing regions within the limbic system. The integration of music-generated auditory and somato-visceral inputs may lead to a synergistic input to the brain that promotes healing. Thus, music can literally heal humans through “touch” as it energizes the brain’s autonomic system for restoring homeostasis.

Keywords: acoustics, brain, music healing, pressure receptors

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Authors: Juan A. Arzate, Funda C. Ertem, M. Nicolas Cruz-Bournazou, Peter Neubauer, Stefan Junne

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— One of the biggest challenges the world faces today is global warming that is caused by greenhouse gases (GHGs) coming from the combustion of fossil fuels for energy generation. In order to mitigate climate change, the European Union has committed to reducing GHG emissions to 80–95% below the level of the 1990s by the year 2050. Renewable technologies are vital to diminish energy-related GHG emissions. Since water and biomass are limited resources, the largest contributions to renewable energy (RE) systems will have to come from wind and solar power. Nevertheless, high proportions of fluctuating RE will present a number of challenges, especially regarding the need to balance the variable energy demand with the weather dependent fluctuation of energy supply. Therefore, biogas plants in this content would play an important role, since they are easily adaptable. Feedstock availability varies locally or seasonally; however there is a lack of knowledge in how biogas plants should be operated in a stable manner by local feedstock. This problem may be prevented through suitable control strategies. Such strategies require the development of convenient mathematical models, which fairly describe the main processes. Modelling allows us to predict the system behavior of biogas plants when different feedstocks are used with different loading rates. Life cycle assessment (LCA) is a technique for analyzing several sides from evolution of a product till its disposal in an environmental point of view. It is highly recommend to use as a decision making tool. In order to achieve suitable strategies, the combination of a flexible energy generation provided by biogas plants, a secure production process and the maximization of the environmental benefits can be obtained by the combination of process modelling and LCA approaches. For this reason, this study focuses on the biogas plant which flexibly generates required energy from the co-digestion of maize, grass and cattle manure, while emitting the lowest amount of GHG´s. To achieve this goal AMOCO model was combined with LCA. The program was structured in Matlab to simulate any biogas process based on the AMOCO model and combined with the equations necessary to obtain climate change, acidification and eutrophication potentials of the whole production system based on ReCiPe midpoint v.1.06 methodology. Developed simulation was optimized based on real data from operating biogas plants and existing literature research. The results prove that AMOCO model can successfully imitate the system behavior of biogas plants and the necessary time required for the process to adapt in order to generate demanded energy from available feedstock. Combination with LCA approach provided opportunity to keep the resulting emissions from operation at the lowest possible level. This would allow for a prediction of the process, when the feedstock utilization supports the establishment of closed material circles within a smart bio-production grid – under the constraint of minimal drawbacks for the environment and maximal sustainability.

Keywords: AMOCO model, GHG emissions, life cycle assessment, modelling

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Authors: Petros M. Chronopoulos, Evangelos Z. Astreinidis

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A major issue of the structural assessment and rehabilitation of existing RC structures is the inadequate lap-splicing of the longitudinal reinforcement. Although prohibited by modern Design Codes, the practice of arranging lap-splices inside the critical regions of RC elements was commonly applied in the past. Today this practice is still the rule, at least for conventional new buildings. Therefore, a lot of relevant research is ongoing in many earthquake prone countries. The rehabilitation of deficient lap-splices of RC elements by means of external confinement is widely accepted as the most efficient technique. If correctly applied, this versatile technique offers a limited increase of flexural capacity and a considerable increase of local ductility and of axial and shear capacities. Moreover, this intervention does not affect the stiffness of the elements and does not affect the dynamic characteristics of the structure. This technique has been extensively discussed and researched contributing to vast accumulation of technical and scientific knowledge that has been reported in relevant books, reports and papers, and included in recent Design Codes and Guides. These references are mostly dealing with modeling and redesign, covering both the enhanced (axial and) shear capacity (due to the additional external closed hoops or jackets) and the increased ductility (due to the confining action, preventing the unzipping of lap-splices and the buckling of continuous reinforcement). An analytical and experimental program devoted to RC members with lap-splices is completed in the Lab. of RC/NTU of Athens/GR. This program aims at the proposal of a rational and safe theoretical model and the calibration of the relevant Design Codes’ provisions. Tests, on forty two (42) full scale specimens, covering mostly beams and columns (not walls), strengthened or not, with adequate or inadequate lap-splices, have been already performed and evaluated. In this paper, the results of twelve (12) specimens under fully reversed cyclic actions are presented and discussed. In eight (8) specimens the lap-splices were inadequate (splicing length of 20 or 30 bar diameters) and they were retrofitted before testing by means of additional external confinement. The two (2) most commonly applied confining materials were used in this study, namely steel and FRPs. More specifically, jackets made of CFRP wraps or light cages made of mild steel were applied. The main parameters of these tests were (i) the degree of confinement (internal and external), and (ii) the length of lap-splices, equal to 20, 30 or 45 bar diameters. These tests were thoroughly instrumented and monitored, by means of conventional (LVDTs, strain gages, etc.) and innovative (optic fibre-Bragg-grating) sensors. This allowed for a thorough investigation of the most influencing design parameter, namely the hoop-stress developed in the confining material. Based on these test results and on comparisons with the provisions of modern Design Codes, it could be argued that shorter (than the normative) lap-splices, commonly found in old structures, could still be effective and safe (at least for lengths more than an absolute minimum), depending on the required ductility, if a properly arranged and adequately detailed external confinement is applied.

Keywords: concrete, fibre-Bragg-grating sensors, lap-splices, retrofitting / rehabilitation

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Authors: Mohosina Jabin Toma, Gerald Tembrevilla, Marina Milner-Bolotin

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Science education in Bangladesh is losing its appeal at an alarming rate due to the lack of science laboratory equipment, excessive teacher-student ratio, and outdated teaching strategies. Research-based educational technologies aim to address some of the problems faced by teachers who have limited access to laboratory resources, like many Bangladeshi teachers. Physics Education Technology (PhET) research team has been developing science and mathematics interactive simulations to help students develop deeper conceptual understanding. Still, PhET simulations are rarely used in Bangladesh. The purpose of this study is to explore Bangladeshi teachers’ challenges in learning to implement PhET-enhanced pedagogies and examine teachers’ views on PhET’s pedagogical opportunities in secondary science education. Since it is a new technology for Bangladesh, seven workshops on PhET were conducted in Dhaka city for 129 in-service and pre-service teachers in the winter of 2023 prior to data collection. This study followed an explanatory mixed method approach that included a pre-and post-workshop survey and five semi-structured interviews. Teachers participated in the workshops voluntarily and shared their experiences at the end. Teachers’ challenges were also identified from workshop discussions and observations. The interviews took place three to four weeks after the workshop and shed light on teachers’ experiences of using PhET in actual classroom settings. The results suggest that teachers had difficulty handling new technology; hence, they recommended preparing a booklet and Bengali YouTube videos on PhET to assist them in overcoming their struggles. Teachers also faced challenges in using any inquiry-based learning approach due to the content-loaded curriculum and exam-oriented education system, as well as limited experience with inquiry-based education. The short duration of classes makes it difficult for them to design PhET activities. Furthermore, considering limited access to computers and the internet in school, teachers think PhET simulations can bring positive changes if used in homework activities. Teachers also think they lack pedagogical skills and sound content knowledge to take full advantage of PhET. They highly appreciated the workshops and proposed that the government designs some teacher training modules on how to incorporate PhET simulations. Despite all the challenges, teachers believe PhET can enhance student learning, ensure student engagement and increase student interest in STEM Education. Considering the lack of science laboratory equipment, teachers recognized the potential of PhET as a supplement to hands-on activities for secondary science education in Bangladesh. They believed that if PhET develops more curriculum-relevant sims, it will bring revolutionary changes to how Bangladeshi students learn science. All the participating teachers in this study came from two organizations, and all the workshops took place in urban areas; therefore, the findings cannot be generalized to all secondary science teachers. A nationwide study is required to include teachers from diverse backgrounds. A further study can shed light on how building a professional learning community can lessen teachers’ challenges in incorporating PhET-enhanced pedagogy in their teaching.

Keywords: educational technology, inquiry-based learning, PhET interactive simulations, PhET-enhanced pedagogies, science education, science laboratory equipment, teacher professional development

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: M. Trousselard, D. Steiler, C. Drogou, P. van-Beers, G. Lamour, S. N. Crosnier, O. Bouilland, P. Dubost, M. Chennaoui, D. Léger

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According to published data, undersea navigation for long periods (nuclear-powered ballistic missile submarine, SSBN) constitutes an extreme environment in which crews are subjected to multiple stresses, including the absence of natural light, illuminance below 1,000 lux, and watch schedules that do not respect natural chronobiological rhythms, for a period of 60-80 days. These stresses seem clearly detrimental to the submariners’ sleep, with consequences for their affective (seasonal affective disorder-like) and cognitive functioning. In the long term, there are abundant publications regarding the consequences of sleep disruption for the occurrence of organic cardiovascular, metabolic, immunological or malignant diseases. It seems essential to propose countermeasures for the duration of the patrol in order to reduce the negative physiological effects on the sleep and mood of submariners. Light therapy, the preferred treatment for dysfunctions of the internal biological clock and the resulting seasonal depression, cannot be used without data to assist knowledge of submariners’ chronobiology (melatonin secretion curve) during patrols, given the unusual characteristics of their working environment. These data are not available in the literature. The aim of this project was to assess, in the course of two studies, the benefits of two environmental techniques for managing chronobiological stress: techniques for optimizing potential (TOP; study 1)3, an existing programme to help in the psychophysiological regulation of stress and sleep in the armed forces, and dawn and dusk simulators (DDS, study 2). For each experiment, psychological, physiological (sleep) or biological (melatonin secretion) data were collected on D20 and D50 of patrol. In the first experiment, we studied sleep and depressive distress in 19 submariners in an operational setting on board an SSBM during a first patrol, and assessed the impact of TOP on the quality of sleep and depressive distress in these same submariners over the course of a second patrol. The submariners were trained in TOP between the two patrols for a 2-month period, at a rate of 1 h of training per week, and assigned daily informal exercises. Results show moderate disruptions in sleep pattern and duration associated with the intensity of depressive distress. The use of TOP during the following patrol improved sleep and depressive mood only in submariners who regularly practiced the techniques. In light of these limited benefits, we assessed, in a second experiment, the benefits of DDS on chronobiology (daily secretion of melatonin) and depressive distress. Ninety submariners were randomly allocated to two groups, group 1 using DDS daily, and group 2 constituting the control group. Although the placebo effect was not controlled, results showed a beneficial effect on chronobiology and depressive mood for submariners with a morning chronotype. Conclusions: These findings demonstrate the difficulty of practicing the tools of psychophysiological management in real life. They raise the question of the subjects’ autonomy with respect to using aids that involve regular practice. It seems important to study autonomy in future studies, as a cognitive resource resulting from the interaction between internal positive resources and “coping” resources, to gain a better understanding of compliance problems.

Keywords: chronobiology, light therapy, seasonal affective disorder, sleep, stress, stress management, submarine

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Authors: Keith Schofield, Garry R. Prentice

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The perceptions of the work an academic does, and the environment in which they do it, contributes to the professional identity of that academic. In turn, this has implications for the level of involvement they have in their job, their satisfaction, and their work product. This research explores academic identities in British and Irish institutions and considers the complex interplay between identity, practice, and participation. Theoretical assumptions made in this paper assert that meaningful work has positive effects on work pride, organisational commitment, organisational citizenship, and motivation; when employees participate enthusiastically they are likely to be more engaged, more successful, and more satisfied. Further examination is given to the context in which this participation happens; the nature of institutional process, management, and relationships with colleagues, team members, and students is considered. The present study follows a mixed-methods approach to explore work satisfaction constructs in a number of academic contexts in the UK and Ireland. The quantitative component of this research (Convenience Sample: 155 academics, and support/ administrative staff; 36.1% male, 63.9% female; 60.8% academic staff, 39.2% support/ administration staff; across a number of universities in the UK and Ireland) was based on an established emotional labour model and was tested across gender groups, job roles, and years of service. This was complimented by qualitative semi-structured interviews (Purposive Sample: 10 academics, and 5 support/ administrative staff across the same universities in the UK and Ireland) to examine various themes including values within academia, work conditions, professional development, and transmission of knowledge to students. Experiences from both academic and support perspectives were sought in order to gain a holistic view of academia and to provide an opportunity to explore the dynamic of the academic/administrator relationship within the broader institutional context. The quantitative emotional labour model, tested via a path analysis, provided a robust description of the relationships within the data. The significant relationships found within the quantitative emotional labour model included a link between non-expression of true feelings resulting in emotional labourious work and lower levels of intrinsic motivation and higher levels of extrinsic motivation. Higher levels of intrinsic motivation also linked positively to work pride. These findings were further explored in the qualitative elements of the research where themes emerged including the disconnection between faculty management and staff, personal fulfilment and the friction between the identities of teacher, researcher/ practitioner and administrator. The implications of the research findings from this study are combined and discussed in relation to possible identity-related and emotional labour management-related interventions. Further, suggestions are made to institutions concerning the application of these findings including the development of academic practices, with specific reference to the duality of identity required to service the combined teacher/ researcher role. Broader considerations of the paper include how individuals and institutions may engage with the changing nature of students-as-consumers as well as a recommendation to centralise personal fulfillment through the development of professional academic identities.

Keywords: academic work, emotional labour, identity friction, mixed methods

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Authors: Claudia Trillo

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Regional innovation eco-ecosystems are composed of a variety of interconnected urban innovation eco-systems, mutually reinforcing each other and making the whole territorial system successful. Combining principles drawn from the new economic growth theory and from the socio-constructivist approach to the economic growth, with the new geography of innovation emerging from the networked nature of innovation districts, this paper explores the spatial configuration of urban innovation districts, with the aim of unveiling replicable spatial patterns and transferable portfolios of urban policies. While some authors suggest that cities should be considered ideal natural clusters, supporting cross-fertilization and innovation thanks to the physical setting they provide to the construction of collective knowledge, still a considerable distance persists between regional development strategies and urban policies. Moreover, while public and private policies supporting entrepreneurship normally consider innovation as the cornerstone of any action aimed at uplifting the competitiveness and economic success of a certain area, a growing body of literature suggests that innovation is non-neutral, hence, it should be constantly assessed against equity and social inclusion. This paper draws from a robust qualitative empirical dataset gathered through 4-years research conducted in Boston to provide readers with an evidence-based set of recommendations drawn from the lessons learned through the investigation of the chosen innovation districts in the Boston area. The evaluative framework used for assessing the overall performance of the chosen case studies stems from the Habitat III Sustainable Development Goals rationale. The concept of inclusive growth has been considered essential to assess the social innovation domain in each of the chosen cases. The key success factors for the development of the Boston innovation ecosystem can be generalized as follows: 1) a quadruple helix model embedded in the physical structure of the two cities (Boston and Cambridge), in which anchor Higher Education (HE) institutions continuously nurture the Entrepreneurial Environment. 2) an entrepreneurial approach emerging from the local governments, eliciting risk-taking and bottom-up civic participation in tackling key issues in the city. 3) a networking structure of some intermediary actors supporting entrepreneurial collaboration, cross-fertilization and co-creation, which collaborate at multiple-scales thus enabling positive spillovers from the stronger to the weaker contexts. 4) awareness of the socio-economic value of the built environment as enabler of cognitive networks allowing activation of the collective intelligence. 5) creation of civic-led spaces enabling grassroot collaboration and cooperation. Evidence shows that there is not a single magic recipe for the successful implementation of place-based and social innovation-driven strategies. On the contrary, the variety of place-grounded combinations of micro and macro initiatives, embedded in the social and spatial fine grain of places and encompassing a diversity of actors, can create the conditions enabling places to thrive and local economic activities to grow in a sustainable way.

Keywords: innovation-driven sustainable Eco-systems , place-based sustainable urban development, sustainable innovation districts, social innovation, urban policie

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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

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

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

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