Search results for: climate change effects on water resources
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 26353

Search results for: climate change effects on water resources

73 Analysis of Vibration and Shock Levels during Transport and Handling of Bananas within the Post-Harvest Supply Chain in Australia

Authors: Indika Fernando, Jiangang Fei, Roger Stanley, Hossein Enshaei

Abstract:

Delicate produce such as fresh fruits are increasingly susceptible to physiological damage during the essential post-harvest operations such as transport and handling. Vibration and shock during the distribution are identified factors for produce damage within post-harvest supply chains. Mechanical damages caused during transit may significantly diminish the quality of fresh produce which may also result in a substantial wastage. Bananas are one of the staple fruit crops and the most sold supermarket produce in Australia. It is also the largest horticultural industry in the state of Queensland where 95% of the total production of bananas are cultivated. This results in significantly lengthy interstate supply chains where fruits are exposed to prolonged vibration and shocks. This paper is focused on determining the shock and vibration levels experienced by packaged bananas during transit from the farm gate to the retail market. Tri-axis acceleration data were captured by custom made accelerometer based data loggers which were set to a predetermined sampling rate of 400 Hz. The devices recorded data continuously for 96 Hours in the interstate journey of nearly 3000 Km from the growing fields in far north Queensland to the central distribution centre in Melbourne in Victoria. After the bananas were ripened at the ripening facility in Melbourne, the data loggers were used to capture the transport and handling conditions from the central distribution centre to three retail outlets within the outskirts of Melbourne. The quality of bananas were assessed before and after transport at each location along the supply chain. Time series vibration and shock data were used to determine the frequency and the severity of the transient shocks experienced by the packages. Frequency spectrogram was generated to determine the dominant frequencies within each segment of the post-harvest supply chain. Root Mean Square (RMS) acceleration levels were calculated to characterise the vibration intensity during transport. Data were further analysed by Fast Fourier Transform (FFT) and the Power Spectral Density (PSD) profiles were generated to determine the critical frequency ranges. It revealed the frequency range in which the escalated energy levels were transferred to the packages. It was found that the vertical vibration was the highest and the acceleration levels mostly oscillated between ± 1g during transport. Several shock responses were recorded exceeding this range which were mostly attributed to package handling. These detrimental high impact shocks may eventually lead to mechanical damages in bananas such as impact bruising, compression bruising and neck injuries which affect their freshness and visual quality. It was revealed that the frequency range between 0-5 Hz and 15-20 Hz exert an escalated level of vibration energy to the packaged bananas which may result in abrasion damages such as scuffing, fruit rub and blackened rub. Further research is indicated specially in the identified critical frequency ranges to minimise exposure of fruits to the harmful effects of vibration. Improving the handling conditions and also further study on package failure mechanisms when exposed to transient shock excitation will be crucial to improve the visual quality of bananas within the post-harvest supply chain in Australia.

Keywords: bananas, handling, post-harvest, supply chain, shocks, transport, vibration

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72 Promoting Environmental Sustainability in Rural Areas with CMUH Green Experiential Education Center

Authors: Yi-Chu Liu, Hsiu-Huei Hung, Li-Hui Yang, Ming-Jyh Chen

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introduction: To promote environmental sustainability, the hospital formed a corporate volunteer team in 2016 to build the Green Experiential Education Center. Our green creation center utilizes attic space to achieve sustainability objectives such as energy efficiency and carbon reduction. Other than executing sustainable plans, the center emphasizes experiential education. We invite our community to actively participate in building a sustainable, economically viable environment. Since 2020, the China Medical University Hospital has provided medical care to the Tgbin community in Taichung City's Heping District. The tribe, primarily composed of Atayal people, the elderly comprise 18% of the total population, and these families' per capita income is relatively low compared to Taiwanese citizens elsewhere. Purpose / Methods: With the experiences at the Green Experiential Education Center, CMUH team identifies the following objectives: Create an aquaponic system to supply vulnerable local households with food. Create a solar renewable energy system to meet the electricity needs of vulnerable local households. Promote the purchase of green electricity certificates to reduce the hospital's carbon emissions and generate additional revenue for the local community. Materials and Methods: In March 2020, we visited the community and installed The aquaponic system in January 2021. CMUH spent 150,000NT (approximately 5000US dollars) in March 2021 to build a 100-square-meter aquaponic system. The production of vegetables and fish caught determines the number of vulnerable families that can be supported. The aquaponics system is a kind of Low energy consumption and environmentally friendly production method, and can simultaneously achieve energy saving, water saving, and fertilizer saving .In September 2023, CMUH will complete a solar renewable energy system. The system will cover an area of 308 square meters and costs approximately NT$240,000 (approximately US$8,000). The installation of electricity meters will enable statistical analysis of power generation. And complete the Taiwan National Renewable Energy Certificate application process. The green electricity certificate will be obtained based on the monthly power generation from the solar renewable energy system. Results: I Food availability and access are crucial considering the remote location and aging population. By creating a fish and vegetable symbiosis system, the vegetables and catches produced will enable economically disadvantaged families to lower food costs. In 2021 and 2022, the aquaponic system produced 52 kilograms of vegetables and 75 kilograms of catch. The production ensures the daily needs of 8 disadvantaged families. Conclusions: The hospital serves as a fortress for public health and the ideal setting for corporate social responsibility. China Medical University Hospital and the Green Experiential Education Center work to strengthen ties with rural communities and offer top-notch specialty medical care. We are committed to assisting people in escaping poverty and hunger as part of the 2030 Sustainable Development Goals.

Keywords: environmental education, sustainability, energy conservation, carbon emissions, rural area development

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71 Fine Characterization of Glucose Modified Human Serum Albumin by Different Biophysical and Biochemical Techniques at a Range

Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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70 The Multiplier Effects of Intelligent Transport System to Nigerian Economy

Authors: Festus Okotie

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Nigeria is the giant of Africa with great and diverse transport potentials yet to be fully tapped into and explored.it is the most populated nation in Africa with nearly 200 million people, the sixth largest oil producer overall and largest oil producer in Africa with proven oil and gas reserves of 37 billion barrels and 192 trillion cubic feet, over 300 square kilometers of arable land and significant deposits of largely untapped minerals. A world bank indicator which measures trading across border ranked Nigeria at 183 out of 185 countries in 2017 and although different governments in the past made efforts through different interventions such as 2007 ports reforms led by Ngozi Okonjo-Iweala, a former minister of Finance and world bank managing director also attempted to resolve some of the challenges such as infrastructure shortcomings, policy and regulatory inconsistencies, overlapping functions and duplicated roles among the different MDA’S. It is one of the fundamental structures smart nations and cities are using to improve the living conditions of its citizens and achieving sustainability. Examples of some of its benefits includes tracking high pedestrian areas, traffic patterns, railway stations, planning and scheduling bus times, it also enhances interoperability, creates alerts of transport situation and has swift capacity to share information among the different platforms and transport modes. It also offers a comprehensive approach to risk management, putting emergency procedures and response capabilities in place, identifying dangers, including vandalism or violence, fare evasion, and medical emergencies. The Nigerian transport system is urgently in need of modern infrastructures such as ITS. Smart city transport technology helps cities to function productively, while improving services for businesses and lives of is citizens. This technology has the ability to improve travel across traditional modes of transport, such as cars and buses, with immediate benefits for city dwellers and also helps in managing transport systems such as dangerous weather conditions, heavy traffic, and unsafe speeds which can result in accidents and loss of lives. Intelligent transportation systems help in traffic control such as permitting traffic lights to react to changing traffic patterns, instead of working on a fixed schedule in traffic. Intelligent transportation systems is very important in Nigeria’s transportation sector and so would require trained personnel to drive its efficiency to greater height because the purpose of introducing it is to add value and at the same time reduce motor vehicle miles and traffic congestion which is a major challenge around Tin can island and Apapa Port, a major transportation hub in Nigeria. The need for the federal government, state governments, houses of assembly to organise a national transportation workshop to begin the process of addressing the challenges in our nation’s transport sector is highly expedient and so bills that will facilitate the implementation of policies to promote intelligent transportation systems needs to be sponsored because of its potentials to create thousands of jobs for our citizens, provide farmers with better access to cities and a better living condition for Nigerians.

Keywords: intelligent, transport, system, Nigeria

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69 Raman Spectral Fingerprints of Healthy and Cancerous Human Colorectal Tissues

Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

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Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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68 The Safe Introduction of Tocilizumab for the Treatment of SARS-CoV-2 Pneumonia at an East London District General Hospital

Authors: Andrew Read, Alice Parry, Kate Woods

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Since the advent of the SARS-CoV-2 pandemic, the search for medications that can reduce mortality and morbidity has been a global research priority. Several multi-center trials have recently demonstrated improved mortality associated with the use of Tocilizumab, an interleukin-6 receptor antagonist, in patients with severe SARS-CoV-2 pneumonia. Initial data supported the administration in patients requiring respiratory support (non-invasive or invasive ventilation), but more recent data has shown benefit in all hypoxic patients. At the height of the second wave of COVID-19 infections in London, our hospital introduced the use of Tocilizumab for patients with severe COVID-19. Tocilizumab is licensed for use in chronic inflammatory conditions and has been associated with an increased risk of severe bacterial and fungal infections, as well as reactivation of chronic viral infections (e.g., hepatitis B). It is a specialist drug that suppresses the formation of C-reactive protein (CRP) for 6 – 12 weeks. It is not widely used by the general medical community. We aimed to assess Tocilizumab use in our hospital and to implement changes to the protocol as required to ensure administration was safe and appropriate. A retrospective study design was used to assess prescriptions over an initial 3-week period in both intensive care and on the medical wards. This amounted to a total of 13 patients. The initial data collection identified four key areas of concern: adherence to national and local inclusion & exclusion criteria; a collection of appropriate screening blood prior to administration; documentation of informed consent or best interest decision and documentation of Tocilizumab administration on patient discharge information, to alert future healthcare providers that typical measures of inflammation and infection, such as CRP, are unreliable for up to 3-months. Data were collected from electronic notes, blood results and observation charts, and cross referenced with pharmacy data. Initial results showed that all four key areas were completed in approximately 50% of cases. Of particular concern was adherence to exclusion criteria, such as current evidence of bacterial infection, and ensuring the correct screening blood was sent to exclude infections such as hepatitis. To remedy this and improve patient safety, the initial data was presented to relevant healthcare professionals. Subsequently, three interventions were introduced and education on each provided to hospital staff. An electronic ‘order set’ collating the appropriate screening blood was created simplifying the screening process. Pre-formed electronic documentation which can be inserted into the notes was created to provide a framework for consent discussions and reduce the time needed for junior doctors to complete this task. Additionally, a ‘Tocilizumab’ administration card was created and administered via pharmacy. This was distributed to each patient on discharge to ensure future healthcare professionals were aware of the potential effects of Tocilizumab administration, including suppression of CRP. Following these changes, repeat data collection over two months illustrated that each of the 4 safety aspects was met with a 100% success rate in every patient. Although this demonstrates good progress and effective interventions the challenge will be to maintain this progress. The audit data collection is ongoing

Keywords: education, patient safety , SARS-CoV-2, Tocilizumab

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67 Evaluation of Random Forest and Support Vector Machine Classification Performance for the Prediction of Early Multiple Sclerosis from Resting State FMRI Connectivity Data

Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

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The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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66 Examining the Behavioral, Hygienic and Expectational Changes in Adolescents and Young Women during COVID-19 Quarantine in Colombia

Authors: Rocio Murad, Marcela Sanchez, Mariana Calderon Jaramillo, Danny Rivera, Angela Cifuentes, Daniela Roldán, Juan Carlos Rivillas

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Women and girls have specific health needs, but during health pandemics such as COVID19 they are less likely to have access to quality essential health information, commodities and services, or insurance coverage for routine and catastrophic health expenses, especially in rural and marginalized communities. This is compounded by multiple or intersecting inequalities, such as ethnicity, socioeconomic status, disability, age, geographic location, and sexual orientation, among others. Despite concerted collective action, there is a lack of information on the situation of women, adolescents and youth, including gender inequalities exacerbated by the pandemic. Much more needs to be done to amplify the lived realities of women and adolescents in global and national advocacy and policy responses. The COVID 19 pandemic reflects the need for systematic advocacy policies based on the lived experiences of women and adolescents, underpinned by human rights. This research is part of the initiative of Profamilia Association (Solidarity Study), and its objective is twofold: i) to analyze the behavioral changes and immediate expectations of Colombians during the stage of relaxation of the confinement measures decreed by the national government; and ii) to identify the needs, experiences and resilient practices of adolescents and young women during the COVID-19 crisis in Colombia. Descriptive analysis of data collected by Profamilia through the Solidaridad study, an exploratory cross-sectional descriptive study that used subnational level data from a nonprobabilistic sample survey conducted to 1735 adults, between September 01 and 11, 2020. Interviews were conducted with key stakeholders about their experiences during COVID19, under three key axes: i) main challenges for adolescents and young women; ii) examples of what has worked well in responding to the challenge; and iii) how/what services are/should be provided during COVID-19 (and beyond) to address the challenge. Interviewees were selected based on prior mapping of social groups of interest. In total, 23 adolescents and young women participated in the interviews. The results show that people adopted behavioral changes such as wearing masks, avoiding people with symptoms, and reducing mobility, but there was also a doubling of concerns for many reasons, from effects on mental health, sexual health, and unattended reproductive health to the burden of care and working at home. The favorable perception that people had at the beginning of the quarantine about the response and actions of the national and local government to control Covid-19 decreased over the course of the quarantine. The challenges and needs of adolescents and young women were highlighted during the most restrictive measures to contain the COVID-19 pandemic, which resulted in disruptions to daily activities, education and work, as well as restrictions to mobility and social interaction. Concerns raised by participants included: impact on mental health and wellbeing due to disruption of daily life; limitations in access to formal and informal education; food insecurity; migration; loss of livelihoods; lack of access to health information and services; limitations to sexual and reproductive health and rights; insecurity problems; and problems in communication and treatment among household members.

Keywords: COVID-19, changes in behavior, adolescents, women

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65 Consumer Preferences for Low-Carbon Futures: A Structural Equation Model Based on the Domestic Hydrogen Acceptance Framework

Authors: Joel A. Gordon, Nazmiye Balta-Ozkan, Seyed Ali Nabavi

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Hydrogen-fueled technologies are rapidly advancing as a critical component of the low-carbon energy transition. In countries historically reliant on natural gas for home heating, such as the UK, hydrogen may prove fundamental for decarbonizing the residential sector, alongside other technologies such as heat pumps and district heat networks. While the UK government is set to take a long-term policy decision on the role of domestic hydrogen by 2026, there are considerable uncertainties regarding consumer preferences for ‘hydrogen homes’ (i.e., hydrogen-fueled appliances for space heating, hot water, and cooking. In comparison to other hydrogen energy technologies, such as road transport applications, to date, few studies have engaged with the social acceptance aspects of the domestic hydrogen transition, resulting in a stark knowledge deficit and pronounced risk to policymaking efforts. In response, this study aims to safeguard against undesirable policy measures by revealing the underlying relationships between the factors of domestic hydrogen acceptance and their respective dimensions: attitudinal, socio-political, community, market, and behavioral acceptance. The study employs an online survey (n=~2100) to gauge how different UK householders perceive the proposition of switching from natural gas to hydrogen-fueled appliances. In addition to accounting for housing characteristics (i.e., housing tenure, property type and number of occupants per dwelling) and several other socio-structural variables (e.g. age, gender, and location), the study explores the impacts of consumer heterogeneity on hydrogen acceptance by recruiting respondents from across five distinct groups: (1) fuel poor householders, (2) technology engaged householders, (3) environmentally engaged householders, (4) technology and environmentally engaged householders, and (5) a baseline group (n=~700) which filters out each of the smaller targeted groups (n=~350). This research design reflects the notion that supporting a socially fair and efficient transition to hydrogen will require parallel engagement with potential early adopters and demographic groups impacted by fuel poverty while also accounting strongly for public attitudes towards net zero. Employing a second-order multigroup confirmatory factor analysis (CFA) in Mplus, the proposed hydrogen acceptance model is tested to fit the data through a partial least squares (PLS) approach. In addition to testing differences between and within groups, the findings provide policymakers with critical insights regarding the significance of knowledge and awareness, safety perceptions, perceived community impacts, cost factors, and trust in key actors and stakeholders as potential explanatory factors of hydrogen acceptance. Preliminary results suggest that knowledge and awareness of hydrogen are positively associated with support for domestic hydrogen at the household, community, and national levels. However, with the exception of technology and/or environmentally engaged citizens, much of the population remains unfamiliar with hydrogen and somewhat skeptical of its application in homes. Knowledge and awareness present as critical to facilitating positive safety perceptions, alongside higher levels of trust and more favorable expectations for community benefits, appliance performance, and potential cost savings. Based on these preliminary findings, policymakers should be put on red alert about diffusing hydrogen into the public consciousness in alignment with energy security, fuel poverty, and net-zero agendas.

Keywords: hydrogen homes, social acceptance, consumer heterogeneity, heat decarbonization

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64 Carbon Nanotube-Based Catalyst Modification to Improve Proton Exchange Membrane Fuel Cell Interlayer Interactions

Authors: Ling Ai, Ziyu Zhao, Zeyu Zhou, Xiaochen Yang, Heng Zhai, Stuart Holmes

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Optimizing the catalyst layer structure is crucial for enhancing the performance of proton exchange membrane fuel cells (PEMFCs) with low Platinum (Pt) loading. Current works focused on the utilization, durability, and site activity of Pt particles on support, and performance enhancement has been achieved by loading Pt onto porous support with different morphology, such as graphene, carbon fiber, and carbon black. Some schemes have also incorporated cost considerations to achieve lower Pt loading. However, the design of the catalyst layer (CL) structure in the membrane electrode assembly (MEA) must consider the interactions between the layers. Addressing the crucial aspects of water management, low contact resistance, and the establishment of effective three-phase boundary for MEA, multi-walled carbon nanotubes (MWCNTs) are promising CL support due to their intrinsically high hydrophobicity, high axial electrical conductivity, and potential for ordered alignment. However, the drawbacks of MWCNTs, such as strong agglomeration, wall surface chemical inertness, and unopened ends, are unfavorable for Pt nanoparticle loading, which is detrimental to MEA processing and leads to inhomogeneous CL surfaces. This further deteriorates the utilization of Pt and increases the contact resistance. Robust chemical oxidation or nitrogen doping can introduce polar functional groups onto the surface of MWCNTs, facilitating the creation of open tube ends and inducing defects in tube walls. This improves dispersibility and load capacity but reduces length and conductivity. Consequently, a trade-off exists between maintaining the intrinsic properties and the degree of functionalization of MWCNTs. In this work, MWCNTs were modified based on the operational requirements of the MEA from the viewpoint of interlayer interactions, including the search for the optimal degree of oxidation, N-doping, and micro-arrangement. MWCNT were functionalized by oxidizing, N-doping, as well as micro-alignment to achieve lower contact resistance between CL and proton exchange membrane (PEM), better hydrophobicity, and enhanced performance. Furthermore, this work expects to construct a more continuously distributed three-phase boundary by aligning MWCNT to form a locally ordered structure, which is essential for the efficient utilization of Pt active sites. Different from other chemical oxidation schemes that used HNO3:H2SO4 (1:3) mixed acid to strongly oxidize MWCNT, this scheme adopted pure HNO3 to partially oxidize MWCNT at a lower reflux temperature (80 ℃) and a shorter treatment time (0 to 10 h) to preserve the morphology and intrinsic conductivity of MWCNT. The maximum power density of 979.81 mw cm-2 was achieved by Pt loading on 6h MWCNT oxidation time (Pt-MWCNT6h). This represented a 59.53% improvement over the commercial Pt/C catalyst of 614.17 (mw cm-2). In addition, due to the stronger electrical conductivity, the charge transfer resistance of Pt-MWCNT6h in the electrochemical impedance spectroscopy (EIS) test was 0.09 Ohm cm-2, which was 48.86% lower than that of Pt/C. This study will discuss the developed catalysts and their efficacy in a working fuel cell system. This research will validate the impact of low-functionalization modification of MWCNTs on the performance of PEMFC, which simplifies the preparation challenges of CL and contributing for the widespread commercial application of PEMFCs on a larger scale.

Keywords: carbon nanotubes, electrocatalyst, membrane electrode assembly, proton exchange membrane fuel cell

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63 Acoustic Radiation Force Impulse Elastography of the Hepatic Tissue of Canine Brachycephalic Patients

Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

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The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

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62 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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61 An Integrated Real-Time Hydrodynamic and Coastal Risk Assessment Model

Authors: M. Reza Hashemi, Chris Small, Scott Hayward

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The Northeast Coast of the US faces damaging effects of coastal flooding and winds due to Atlantic tropical and extratropical storms each year. Historically, several large storm events have produced substantial levels of damage to the region; most notably of which were the Great Atlantic Hurricane of 1938, Hurricane Carol, Hurricane Bob, and recently Hurricane Sandy (2012). The objective of this study was to develop an integrated modeling system that could be used as a forecasting/hindcasting tool to evaluate and communicate the risk coastal communities face from these coastal storms. This modeling system utilizes the ADvanced CIRCulation (ADCIRC) model for storm surge predictions and the Simulating Waves Nearshore (SWAN) model for the wave environment. These models were coupled, passing information to each other and computing over the same unstructured domain, allowing for the most accurate representation of the physical storm processes. The coupled SWAN-ADCIRC model was validated and has been set up to perform real-time forecast simulations (as well as hindcast). Modeled storm parameters were then passed to a coastal risk assessment tool. This tool, which is generic and universally applicable, generates spatial structural damage estimate maps on an individual structure basis for an area of interest. The required inputs for the coastal risk model included a detailed information about the individual structures, inundation levels, and wave heights for the selected region. Additionally, calculation of wind damage to structures was incorporated. The integrated coastal risk assessment system was then tested and applied to Charlestown, a small vulnerable coastal town along the southern shore of Rhode Island. The modeling system was applied to Hurricane Sandy and a synthetic storm. In both storm cases, effect of natural dunes on coastal risk was investigated. The resulting damage maps for the area (Charlestown) clearly showed that the dune eroded scenarios affected more structures, and increased the estimated damage. The system was also tested in forecast mode for a large Nor’Easters: Stella (March 2017). The results showed a good performance of the coupled model in forecast mode when compared to observations. Finally, a nearshore model XBeach was then nested within this regional grid (ADCIRC-SWAN) to simulate nearshore sediment transport processes and coastal erosion. Hurricane Irene (2011) was used to validate XBeach, on the basis of a unique beach profile dataset at the region. XBeach showed a relatively good performance, being able to estimate eroded volumes along the beach transects with a mean error of 16%. The validated model was then used to analyze the effectiveness of several erosion mitigation methods that were recommended in a recent study of coastal erosion in New England: beach nourishment, coastal bank (engineered core), and submerged breakwater as well as artificial surfing reef. It was shown that beach nourishment and coastal banks perform better to mitigate shoreline retreat and coastal erosion.

Keywords: ADCIRC, coastal flooding, storm surge, coastal risk assessment, living shorelines

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60 A Comprehensive Approach to Create ‘Livable Streets’ in the Mixed Land Use of Urban Neighborhoods: A Case Study of Bangalore Street

Authors: K. C. Tanuja, Mamatha P. Raj

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"People have always lived on streets. They have been the places where children first learned about the world, where neighbours met, the social centres of towns and cities, the rallying points for revolts, the scenes of repression. The street has always been the scene of this conflict, between living and access, between resident and traveller, between street life and the threat of death.” Livable Streets by Donald Appleyard. Urbanisation is happening rapidly all over the world. As population increasing in the urban settlements, its required to provide quality of life to all the inhabitants who live in. Urban design is a place making strategic planning. Urban design principles promote visualising any place environmentally, socially and economically viable. Urban design strategies include building mass, transit development, economic viability and sustenance and social aspects. Cities are wonderful inventions of diversity- People, things, activities, ideas and ideologies. Cities should be smarter and adjustable to present technology and intelligent system. Streets represent the community in terms of social and physical aspects. Streets are an urban form that responds to many issues and are central to urban life. Streets are for livability, safety, mobility, place of interest, economic opportunity, balancing the ecology and for mass transit. Urban streets are places where people walk, shop, meet and engage in different types of social and recreational activities which make urban community enjoyable. Streets knit the urban fabric of activities. Urban streets become livable with the introduction of social network enhancing the pedestrian character by providing good design features which in turn should achieve the minimal impact of motor vehicle use on pedestrians. Livable streets are the spatial definition to the public right of way on urban streets. Streets in India have traditionally been the public spaces where social life happened or created from ages. Streets constitute the urban public realm where people congregate, celebrate and interact. Streets are public places that can promote social interaction, active living and community identity. Streets as potential contributors to a better living environment, knitting together the urban fabric of people and places that make up a community. Livable streets or complete streets are making our streets as social places, roadways and sidewalks accessible, safe, efficient and useable for all people. The purpose of this paper is to understand the concept of livable street and parameters of livability on urban streets. Streets to be designed as the pedestrians are the main users and create spaces and furniture for social interaction which serves for the needs of the people of all ages and abilities. The problems of streets like congestion due to width of the street, traffic movement and adjacent land use and type of movement need to be redesigned and improve conditions defining the clear movement path for vehicles and pedestrians. Well-designed spatial qualities of street enhances the street environment, livability and then achieves quality of life to the pedestrians. A methodology been derived to arrive at the typologies in street design after analysis of existing situation and comparing with livable standards. It was Donald Appleyard‟s Livable Streets laid out the social effects on streets creating the social network to achieve Livable Streets.

Keywords: livable streets, social interaction, pedestrian use, urban design

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59 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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58 Developing Primal Teachers beyond the Classroom: The Quadrant Intelligence (Q-I) Model

Authors: Alexander K. Edwards

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Introduction: The moral dimension of teacher education globally has assumed a new paradigm of thinking based on the public gain (return-on-investments), value-creation (quality), professionalism (practice), and business strategies (innovations). Abundant literature reveals an interesting revolutionary trend in complimenting the raising of teachers and academic performances. Because of the global competition in the knowledge-creation and service areas, the C21st teacher at all levels is expected to be resourceful, strategic thinker, socially intelligent, relationship aptitude, and entrepreneur astute. This study is a significant contribution to practice and innovations to raise exemplary or primal teachers. In this study, the qualities needed were considered as ‘Quadrant Intelligence (Q-i)’ model for a primal teacher leadership beyond the classroom. The researcher started by examining the issue of the majority of teachers in Ghana Education Services (GES) in need of this Q-i to be effective and efficient. The conceptual framing became determinants of such Q-i. This is significant for global employability and versatility in teacher education to create premium and primal teacher leadership, which are again gaining high attention in scholarship due to failing schools. The moral aspect of teachers failing learners is a highly important discussion. In GES, some schools score zero percent at the basic education certificate examination (BECE). The question is what will make any professional teacher highly productive, marketable, and an entrepreneur? What will give teachers the moral consciousness of doing the best to succeed? Method: This study set out to develop a model for primal teachers in GES as an innovative way to highlight a premium development for the C21st business-education acumen through desk reviews. The study is conceptually framed by examining certain skill sets such as strategic thinking, social intelligence, relational and emotional intelligence and entrepreneurship to answer three main burning questions and other hypotheses. Then the study applied the causal comparative methodology with a purposive sampling technique (N=500) from CoE, GES, NTVI, and other teachers associations. Participants responded to a 30-items, researcher-developed questionnaire. Data is analyzed on the quadrant constructs and reported as ex post facto analyses of multi-variances and regressions. Multiple associations were established for statistical significance (p=0.05). Causes and effects are postulated for scientific discussions. Findings: It was found out that these quadrants are very significant in teacher development. There were significant variations in the demographic groups. However, most teachers lack considerable skills in entrepreneurship, leadership in teaching and learning, and business thinking strategies. These have significant effect on practices and outcomes. Conclusion and Recommendations: It is quite conclusive therefore that in GES teachers may need further instructions in innovations and creativity to transform knowledge-creation into business venture. In service training (INSET) has to be comprehensive. Teacher education curricula at Colleges may have to be re-visited. Teachers have the potential to raise their social capital, to be entrepreneur, and to exhibit professionalism beyond their community services. Their primal leadership focus will benefit many clienteles including students and social circles. Recommendations examined the policy implications for curriculum design, practice, innovations and educational leadership.

Keywords: emotional intelligence, entrepreneurship, leadership, quadrant intelligence (q-i), primal teacher leadership, strategic thinking, social intelligence

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57 A Study on the Relation among Primary Care Professionals Serving Disadvantaged Community, Socioeconomic Status, and Adverse Health Outcome

Authors: Chau-Kuang Chen, Juanita Buford, Colette Davis, Raisha Allen, John Hughes, James Tyus, Dexter Samuels

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During the post-Civil War era, the city of Nashville, Tennessee, had the highest mortality rate in the country. The elevated death and disease among ex-slaves were attributable to the unavailability of healthcare. To address the paucity of healthcare services, the College, an institution with the mission of educating minority professionals and serving the under served population, was established in 1876. This study was designed to assess if the College has accomplished its mission of serving under served communities and contributed to the elimination of health disparities in the United States. The study objective was to quantify the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities, which, in turn, was significantly associated with a health professional shortage score partly designated by the U.S. Department of Health and Human Services. Various statistical methods were used to analyze the alumni data in years 1975 – 2013. K-means cluster analysis was utilized to identify individual medical and dental graduates into the cluster groups of the practice communities (Disadvantaged or Non-disadvantaged Communities). Discriminant analysis was implemented to verify the classification accuracy of cluster analysis. The independent t test was performed to detect the significant mean differences for clustering and criterion variables between Disadvantaged and Non-disadvantaged Communities, which confirms the “content” validity of cluster analysis model. Chi-square test was used to assess if the proportion of cluster groups (Disadvantaged vs Non-disadvantaged Communities) were consistent with that of practicing specialties (primary care vs. non-primary care). Finally, the partial least squares (PLS) path model was constructed to explore the “construct” validity of analytics model by providing the magnitude effects of socioeconomic status and adverse health outcome on primary care professionals serving disadvantaged community. The social ecological theory along with statistical models mentioned was used to establish the relationship between medical and dental graduates (primary care professionals serving disadvantaged communities) and their social environments (socioeconomic status, adverse health outcome, health professional shortage score). Based on social ecological framework, it was hypothesized that the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities could be quantified. Also, primary care professionals serving disadvantaged communities related to a health professional shortage score can be measured. Adverse health outcome (adult obesity rate, age-adjusted premature mortality rate, and percent of people diagnosed with diabetes) could be affected by the latent variable, namely socioeconomic status (unemployment rate, poverty rate, percent of children who were in free lunch programs, and percent of uninsured adults). The study results indicated that approximately 83% (3,192/3,864) of the College’s medical and dental graduates from 1975 to 2013 were practicing in disadvantaged communities. In addition, the PLS path modeling demonstrated that primary care professionals serving disadvantaged community was significantly associated with socioeconomic status and adverse health outcome (p < .001). In summary, the majority of medical and dental graduates from the College provide primary care services to disadvantaged communities with low socioeconomic status and high adverse health outcomes, which demonstrate that the College has fulfilled its mission.

Keywords: disadvantaged community, K-means cluster analysis, PLS path modeling, primary care

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56 The Potential of Rhizospheric Bacteria for Mycotoxigenic Fungi Suppression

Authors: Vanja Vlajkov, Ivana PajčIn, Mila Grahovac, Marta Loc, Dragana Budakov, Jovana Grahovac

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The rhizosphere soil refers to the plant roots' dynamic environment characterized by their inhabitants' high biological activity. Rhizospheric bacteria are recognized as effective biocontrol agents and considered cardinal in alternative strategies for securing ecological plant diseases management. The need to suppress fungal pathogens is an urgent task, not only because of the direct economic losses caused by infection but also due to their ability to produce mycotoxins with harmful effects on human health. Aspergillus and Fusarium species are well-known producers of toxigenic metabolites with a high capacity to colonize crops and enter the food chain. The bacteria belonging to the Bacillus genus has been conceded as a plant beneficial species in agricultural practice and identified as plant growth-promoting rhizobacteria (PGPR). Besides incontestable potential, the full commercialization of microbial biopesticides is in the preliminary phase. Thus, there is a constant need for estimating the suitability of novel strains to be used as a central point of viable bioprocess leading to market-ready product development. In the present study, 76 potential producing strains were isolated from the rhizosphere soil, sampled from different localities in the Autonomous Province of Vojvodina, Republic of Serbia. The selective isolation process of strains started by resuspending 1 g of soil samples in 9 ml of saline and incubating at 28° C for 15 minutes at 150 rpm. After homogenization, thermal treatment at 100° C for 7 minutes was performed. Dilution series (10-1-10-3) were prepared, and 500 µl of each was inoculated on nutrient agar plates and incubated at 28° C for 48 h. The pure cultures of morphologically different strains indicating belonging to the Bacillus genus were obtained by the spread-plate technique. The cultivation of the isolated strains was carried out in an Erlenmeyer flask for 96 h, at 28 °C, 170 rpm. The antagonistic activity screening included two phytopathogenic fungi as test microorganisms: Aspergillus sp. and Fusarium sp. The mycelial growth inhibition was estimated based on the antimicrobial activity testing of cultivation broth by the diffusion method. For the Aspergillus sp., the highest antifungal activity was recorded for the isolates Kro-4a and Mah-1a. In contrast, for the Fusarium sp., following 15 isolates exhibited the highest antagonistic effect Par-1, Par-2, Par-3, Par-4, Kup-4, Paš-1b, Pap-3, Kro-2, Kro-3a, Kro-3b, Kra-1a, Kra-1b, Šar-1, Šar-2b and Šar-4. One-way ANOVA was performed to determine the antagonists' effect statistical significance on inhibition zone diameter. Duncan's multiple range test was conducted to define homogenous groups of antagonists with the same level of statistical significance regarding their effect on antimicrobial activity of the tested cultivation broth against tested pathogens. The study results have pointed out the significant in vitro potential of the isolated strains to be used as biocontrol agents for the suppression of the tested mycotoxigenic fungi. Further research should include the identification and detailed characterization of the most promising isolates and mode of action of the selected strains as biocontrol agents. The following research should also involve bioprocess optimization steps to fully reach the selected strains' potential as microbial biopesticides and design cost-effective biotechnological production.

Keywords: Bacillus, biocontrol, bioprocess, mycotoxigenic fungi

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55 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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54 Microstructural Characterization of Bitumen/Montmorillonite/Isocyanate Composites by Atomic Force Microscopy

Authors: Francisco J. Ortega, Claudia Roman, Moisés García-Morales, Francisco J. Navarro

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Asphaltic bitumen has been largely used in both industrial and civil engineering, mostly in pavement construction and roofing membrane manufacture. However, bitumen as such is greatly susceptible to temperature variations, and dramatically changes its in-service behavior from a viscoelastic liquid, at medium-high temperatures, to a brittle solid at low temperatures. Bitumen modification prevents these problems and imparts improved performance. Isocyanates like polymeric MDI (mixture of 4,4′-diphenylmethane di-isocyanate, 2,4’ and 2,2’ isomers, and higher homologues) have shown to remarkably enhance bitumen properties at the highest in-service temperatures expected. This comes from the reaction between the –NCO pendant groups of the oligomer and the most polar groups of asphaltenes and resins in bitumen. In addition, oxygen diffusion and/or UV radiation may provoke bitumen hardening and ageing. With the purpose of minimizing these effects, nano-layered-silicates (nanoclays) are increasingly being added to bitumen formulations. Montmorillonites, a type of naturally occurring mineral, may produce a nanometer scale dispersion which improves bitumen thermal, mechanical and barrier properties. In order to increase their lipophilicity, these nanoclays are normally treated so that organic cations substitute the inorganic cations located in their intergallery spacing. In the present work, the combined effect of polymeric MDI and the commercial montmorillonite Cloisite® 20A was evaluated. A selected bitumen with penetration within the range 160/220 was modified with 10 wt.% Cloisite® 20A and 2 wt.% polymeric MDI, and the resulting ternary composites were characterized by linear rheology, X-ray diffraction (XRD) and Atomic Force Microscopy (AFM). The rheological tests evidenced a notable solid-like behavior at the highest temperatures studied when bitumen was just loaded with 10 wt.% Cloisite® 20A and high-shear blended for 20 minutes. However, if polymeric MDI was involved, the sequence of addition exerted a decisive control on the linear rheology of the final ternary composites. Hence, in bitumen/Cloisite® 20A/polymeric MDI formulations, the previous solid-like behavior disappeared. By contrast, an inversion in the order of addition (bitumen/polymeric MDI/ Cloisite® 20A) enhanced further the solid-like behavior imparted by the nanoclay. In order to gain a better understanding of the factors that govern the linear rheology of these ternary composites, a morphological and microstructural characterization based on XRD and AFM was conducted. XRD demonstrated the existence of clay stacks intercalated by bitumen molecules to some degree. However, the XRD technique cannot provide detailed information on the extent of nanoclay delamination, unless the entire fraction has effectively been fully delaminated (situation in which no peak is observed). Furthermore, XRD was unable to provide precise knowledge neither about the spatial distribution of the intercalated/exfoliated platelets nor about the presence of other structures at larger length scales. In contrast, AFM proved its power at providing conclusive information on the morphology of the composites at the nanometer scale and at revealing the structural modification that yielded the rheological properties observed. It was concluded that high-shear blending brought about a nanoclay-reinforced network. As for the bitumen/Cloisite® 20A/polymeric MDI formulations, the solid-like behavior was destroyed as a result of the agglomeration of the nanoclay platelets promoted by chemical reactions.

Keywords: Atomic Force Microscopy, bitumen, composite, isocyanate, montmorillonite.

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53 Fuzzy Data, Random Drift, and a Theoretical Model for the Sequential Emergence of Religious Capacity in Genus Homo

Authors: Margaret Boone Rappaport, Christopher J. Corbally

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The ancient ape ancestral population from which living great ape and human species evolved had demographic features affecting their evolution. The population was large, had great genetic variability, and natural selection was effective at honing adaptations. The emerging populations of chimpanzees and humans were affected more by founder effects and genetic drift because they were smaller. Natural selection did not disappear, but it was not as strong. Consequences of the 'population crash' and the human effective population size are introduced briefly. The history of the ancient apes is written in the genomes of living humans and great apes. The expansion of the brain began before the human line emerged. Coalescence times for some genes are very old – up to several million years, long before Homo sapiens. The mismatch between gene trees and species trees highlights the anthropoid speciation processes, and gives the human genome history a fuzzy, probabilistic quality. However, it suggests traits that might form a foundation for capacities emerging later. A theoretical model is presented in which the genomes of early ape populations provide the substructure for the emergence of religious capacity later on the human line. The model does not search for religion, but its foundations. It suggests a course by which an evolutionary line that began with prosimians eventually produced a human species with biologically based religious capacity. The model of the sequential emergence of religious capacity relies on cognitive science, neuroscience, paleoneurology, primate field studies, cognitive archaeology, genomics, and population genetics. And, it emphasizes five trait types: (1) Documented, positive selection of sensory capabilities on the human line may have favored survival, but also eventually enriched human religious experience. (2) The bonobo model suggests a possible down-regulation of aggression and increase in tolerance while feeding, as well as paedomorphism – but, in a human species that remains cognitively sharp (unlike the bonobo). The two species emerged from the same ancient ape population, so it is logical to search for shared traits. (3) An up-regulation of emotional sensitivity and compassion seems to have occurred on the human line. This finds support in modern genetic studies. (4) The authors’ published model of morality's emergence in Homo erectus encompasses a cognitively based, decision-making capacity that was hypothetically overtaken, in part, by religious capacity. Together, they produced a strong, variable, biocultural capability to support human sociability. (5) The full flowering of human religious capacity came with the parietal expansion and smaller face (klinorhynchy) found only in Homo sapiens. Details from paleoneurology suggest the stage was set for human theologies. Larger parietal lobes allowed humans to imagine inner spaces, processes, and beings, and, with the frontal lobe, led to the first theologies composed of structured and integrated theories of the relationships between humans and the supernatural. The model leads to the evolution of a small population of African hominins that was ready to emerge with religious capacity when the species Homo sapiens evolved two hundred thousand years ago. By 50-60,000 years ago, when human ancestors left Africa, they were fully enabled.

Keywords: genetic drift, genomics, parietal expansion, religious capacity

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52 A Qualitative Exploration of the Sexual and Reproductive Health Practices of Adolescent Mothers from Indigenous Populations in Ratanak Kiri Province, Cambodia

Authors: Bridget J. Kenny, Elizabeth Hoban, Jo Williams

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Adolescent pregnancy presents a significant public health challenge for Cambodia. Despite declines in the overall fertility rate, the adolescent fertility rate is increasing. Adolescent pregnancy is particularly problematic in the Northeast provinces of Ratanak Kiri and Mondul Kiri where 34 percent of girls aged between 15 and 19 have begun childbearing; this is almost three times Cambodia’s national average of 12 percent. Language, cultural and geographic barriers have restricted qualitative exploration of the sexual and reproductive health (SRH) challenges that face indigenous adolescents in Northeast Cambodia. The current study sought to address this gap by exploring the SRH practices of adolescent mothers from indigenous populations in Ratanak Kiri Province. Twenty-two adolescent mothers, aged between 15 and 19, were recruited from seven indigenous villages in Ratanak Kiri Province and asked to participate in a combined body mapping exercise and semi-structured interview. Participants were given a large piece of paper (59.4 x 84.1 cm) with the outline of a female body and asked to draw the female reproductive organs onto the ‘body map’. Participants were encouraged to explain what they had drawn with the purpose of evoking conversation about their reproductive bodies. Adolescent mothers were then invited to participate in a semi-structured interview to further expand on topics of SRH. The qualitative approach offered an excellent avenue to explore the unique SRH challenges that face indigenous adolescents in rural Cambodia. In particular, the use of visual data collection methods reduced the language and cultural barriers that have previously restricted or prevented qualitative exploration of this population group. Thematic analysis yielded six major themes: (1) understanding of the female reproductive body, (2) contraceptive knowledge, (3) contraceptive use, (4) barriers to contraceptive use, (5) sexual practices, (6) contact with healthcare facilities. Participants could name several modern contraceptive methods and knew where they could access family planning services. However, adolescent mothers explained that they gained this knowledge during antenatal care visits and consequently participants had limited SRH knowledge, including contraceptive awareness, at the time of sexual initiation. Fear of the perceived side effects of modern contraception, including infertility, provided an additional barrier to contraceptive use for indigenous adolescents. Participants did not cite cost or geographic isolation as barriers to accessing SRH services. Child marriage and early sexual initiation were also identified as important factors contributing to the high prevalence of adolescent pregnancy in this population group. The findings support the Ministry of Education, Youth and Sports' (MoEYS) recent introduction of SRH education into the primary and secondary school curriculum but suggest indigenous girls in rural Cambodia require additional sources of SRH information. Results indicate adolescent girls’ first point of contact with healthcare facilities occurs after they become pregnant. Promotion of an effective continuum of care by increasing access to healthcare services during the pre-pregnancy period is suggested as a means of providing adolescents girls with an additional avenue to acquire SRH information.

Keywords: adolescent pregnancy, contraceptive use, family planning, sexual and reproductive health

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51 Biodeterioration and Biodegradation of Historic Parks of UK by Algae

Authors: Syeda Fatima Manzelat

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The present study aims to study the groups of algal genera that are responsible for the biodeterioration, biodegradation, and biological pollution of the structures and features of the two historic parks of the UK. Different sites of Campbell Park and Great Linford Manor Park in Milton Keynes are selected to study the morphological, aesthetic, and physical effects of the algal growth. Specimens and swabs were collected mechanically from selected sites. Algal specimens are preserved in Lugol’s solution and labelled with standard information. Photomicrograph analysis of slides using taxonomic keys and visual observation identified algal species that are homogenously and non-homogenously mixed in the aerial, terrestrial, and aquatic habitats. A qualitative study revealed seven classes of Algae. Most of the algal genera isolated have proven records of potential biodegradation, discoloration, and biological pollution. Chlorophyceae was predominantly represented by eleven genera: Chlorella, Chlorococcum Cladophora, Coenochloris Cylindrocapsa, Microspora, Prasiola, Spirogyra, Trentepholia, Ulothrix and Zygnema. Charophyceae is represented by four genera: Cosmarium, Klebsormidium, Mesotaenium, and Mougeotia. Xanthophyceae with two genera, Tribonema and Vaucheria. Bacillariophyceae (Diatoms) are represented by six genera: Acnanthes, Bacillaria, Fragilaria, Gomphonema, Synedra, and Tabellaria, Dinophyceae with a Dinoflagellate. Rhodophyceae included Bangia and Batrachospermum, Cyanophyceae with five genera, Chroococcus, Gloeocapsa, Scytonema, Stigonema and Oscillatoria. The quantitative analysis by statistical method revealed that Chlorophyceae was the predominant class, with eleven genera isolated from different sites of the two parks. Coenochloris of Chlorophyceae was isolated from thirteen sites during the study, followed by Gloeocapsa of Cyanophyceae, which is isolated from 12 sites. These two algae impart varying shades of green colour on the surfaces on which they form biofilms. Prasiola, Vaucheria, and Trentepholia were isolated only from Great Linford Park. Trentepholia imparted a significant orange colour to the walls and trees of the sites. The compounds present in algae that are responsible for discoloration are the green pigment chlorophyll, orange pigment β-carotene, and yellow pigment quinone. Mesotaenium, Dinoflagellate, Gomphonema, Fragilaria, Tabellaria and two unidentified genera were isolated from Campbell Park only. Largest number of algal genera (25) were isolated from the canal of Campbell Park followed by (21) from the canal at Great Linford Manor Park. The Algae were found to grow on surfaces of walls, wooden fencings, metal sculptures, and railings. The Algae are reported to induce surface erosion, natural weathering, and cracking, leading to technical and mechanical instability and extensive damage to building materials. The algal biofilms secrete different organic acids, which are responsible for biosolubilization and biodeterioration of the building materials. The aquatic algal blooms isolated during the study release toxins which are responsible for allergy, skin rashes, vomiting, diarrhea, fever, muscle spasms, and lung and throat infections. The study identifies the places and locations at the historic sites which need to be paid attention. It provides an insight to the conservation strategies to overcome the negative impacts of bio colonization by algae. Prevention measures by different treatments need to be regularly monitored.

Keywords: algae, biodegradation, historic gardens, UK

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50 Self-Medication with Antibiotics, Evidence of Factors Influencing the Practice in Low and Middle-Income Countries: A Systematic Scoping Review

Authors: Neusa Fernanda Torres, Buyisile Chibi, Lyn E. Middleton, Vernon P. Solomon, Tivani P. Mashamba-Thompson

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Background: Self-medication with antibiotics (SMA) is a global concern, with a higher incidence in low and middle-income countries (LMICs). Despite intense world-wide efforts to control and promote the rational use of antibiotics, continuing practices of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and other undesirable antibiotic side effects. Moreover, it increases the health systems costs of acquiring more powerful antibiotics to treat the resistant infection. This review thus maps evidence on the factors influencing self-medication with antibiotics in these settings. Methods: The search strategy for this review involved electronic databases including PubMed, Web of Knowledge, Science Direct, EBSCOhost (PubMed, CINAHL with Full Text, Health Source - Consumer Edition, MEDLINE), Google Scholar, BioMed Central and World Health Organization library, using the search terms:’ Self-Medication’, ‘antibiotics’, ‘factors’ and ‘reasons’. Our search included studies published from 2007 to 2017. Thematic analysis was performed to identify the patterns of evidence on SMA in LMICs. The mixed method quality appraisal tool (MMAT) version 2011 was employed to assess the quality of the included primary studies. Results: Fifteen studies met the inclusion criteria. Studies included population from the rural (46,4%), urban (33,6%) and combined (20%) settings, of the following LMICs: Guatemala (2 studies), India (2), Indonesia (2), Kenya (1), Laos (1), Nepal (1), Nigeria (2), Pakistan (2), Sri Lanka (1), and Yemen (1). The total sample size of all 15 included studies was 7676 participants. The findings of the review show a high prevalence of SMA ranging from 8,1% to 93%. Accessibility, affordability, conditions of health facilities (long waiting, quality of services and workers) as long well as poor health-seeking behavior and lack of information are factors that influence SMA in LMICs. Antibiotics such as amoxicillin, metronidazole, amoxicillin/clavulanic, ampicillin, ciprofloxacin, azithromycin, penicillin, and tetracycline, were the most frequently used for SMA. The major sources of antibiotics included pharmacies, drug stores, leftover drugs, family/friends and old prescription. Sore throat, common cold, cough with mucus, headache, toothache, flu-like symptoms, pain relief, fever, running nose, toothache, upper respiratory tract infections, urinary symptoms, urinary tract infection were the common disease symptoms managed with SMA. Conclusion: Although the information on factors influencing SMA in LMICs is unevenly distributed, the available information revealed the existence of research evidence on antibiotic self-medication in some countries of LMICs. SMA practices are influenced by social-cultural determinants of health and frequently associated with poor dispensing and prescribing practices, deficient health-seeking behavior and consequently with inappropriate drug use. Therefore, there is still a need to conduct further studies (qualitative, quantitative and randomized control trial) on factors and reasons for SMA to correctly address the public health problem in LMICs.

Keywords: antibiotics, factors, reasons, self-medication, low and middle-income countries (LMICs)

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49 A Case Study Report on Acoustic Impact Assessment and Mitigation of the Hyprob Research Plant

Authors: D. Bianco, A. Sollazzo, M. Barbarino, G. Elia, A. Smoraldi, N. Favaloro

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The activities, described in the present paper, have been conducted in the framework of the HYPROB-New Program, carried out by the Italian Aerospace Research Centre (CIRA) promoted and funded by the Italian Ministry of University and Research (MIUR) in order to improve the National background on rocket engine systems for space applications. The Program has the strategic objective to improve National system and technology capabilities in the field of liquid rocket engines (LRE) for future Space Propulsion Systems applications, with specific regard to LOX/LCH4 technology. The main purpose of the HYPROB program is to design and build a Propulsion Test Facility (HIMP) allowing test activities on Liquid Thrusters. The development of skills in liquid rocket propulsion can only pass through extensive test campaign. Following its mission, CIRA has planned the development of new testing facilities and infrastructures for space propulsion characterized by adequate sizes and instrumentation. The IMP test cell is devoted to testing articles representative of small combustion chambers, fed with oxygen and methane, both in liquid and gaseous phase. This article describes the activities that have been carried out for the evaluation of the acoustic impact, and its consequent mitigation. The impact of the simulated acoustic disturbance has been evaluated, first, using an approximated method based on experimental data by Baumann and Coney, included in “Noise and Vibration Control Engineering” edited by Vér and Beranek. This methodology, used to evaluate the free-field radiation of jet in ideal acoustical medium, analyzes in details the jet noise and assumes sources acting at the same time. It considers as principal radiation sources the jet mixing noise, caused by the turbulent mixing of jet gas and the ambient medium. Empirical models, allowing a direct calculation of the Sound Pressure Level, are commonly used for rocket noise simulation. The model named after K. Eldred is probably one of the most exploited in this area. In this paper, an improvement of the Eldred Standard model has been used for a detailed investigation of the acoustical impact of the Hyprob facility. This new formulation contains an explicit expression for the acoustic pressure of each equivalent noise source, in terms of amplitude and phase, allowing the investigation of the sources correlation effects and their propagation through wave equations. In order to enhance the evaluation of the facility acoustic impact, including an assessment of the mitigation strategies to be set in place, a more advanced simulation campaign has been conducted using both an in-house code for noise propagation and scattering, and a commercial code for industrial noise environmental impact, CadnaA. The noise prediction obtained with the revised Eldred-based model has then been used for formulating an empirical/BEM (Boundary Element Method) hybrid approach allowing the evaluation of the barrier mitigation effect, at the design. This approach has been compared with the analogous empirical/ray-acoustics approach, implemented within CadnaA using a customized definition of sources and directivity factor. The resulting impact evaluation study is reported here, along with the design-level barrier optimization for noise mitigation.

Keywords: acoustic impact, industrial noise, mitigation, rocket noise

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48 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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47 Large Scale Method to Assess the Seismic Vulnerability of Heritage Buidings: Modal Updating of Numerical Models and Vulnerability Curves

Authors: Claire Limoge Schraen, Philippe Gueguen, Cedric Giry, Cedric Desprez, Frédéric Ragueneau

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Mediterranean area is characterized by numerous monumental or vernacular masonry structures illustrating old ways of build and live. Those precious buildings are often poorly documented, present complex shapes and loadings, and are protected by the States, leading to legal constraints. This area also presents a moderate to high seismic activity. Even moderate earthquakes can be magnified by local site effects and cause collapse or significant damage. Moreover the structural resistance of masonry buildings, especially when less famous or located in rural zones has been generally lowered by many factors: poor maintenance, unsuitable restoration, ambient pollution, previous earthquakes. Recent earthquakes prove that any damage to these architectural witnesses to our past is irreversible, leading to the necessity of acting preventively. This means providing preventive assessments for hundreds of structures with no or few documents. In this context we want to propose a general method, based on hierarchized numerical models, to provide preliminary structural diagnoses at a regional scale, indicating whether more precise investigations and models are necessary for each building. To this aim, we adapt different tools, being developed such as photogrammetry or to be created such as a preprocessor starting from pictures to build meshes for a FEM software, in order to allow dynamic studies of the buildings of the panel. We made an inventory of 198 baroque chapels and churches situated in the French Alps. Then their structural characteristics have been determined thanks field surveys and the MicMac photogrammetric software. Using structural criteria, we determined eight types of churches and seven types for chapels. We studied their dynamical behavior thanks to CAST3M, using EC8 spectrum and accelerogramms of the studied zone. This allowed us quantifying the effect of the needed simplifications in the most sensitive zones and choosing the most effective ones. We also proposed threshold criteria based on the observed damages visible in the in situ surveys, old pictures and Italian code. They are relevant in linear models. To validate the structural types, we made a vibratory measures campaign using vibratory ambient noise and velocimeters. It also allowed us validating this method on old masonry and identifying the modal characteristics of 20 churches. Then we proceeded to a dynamic identification between numerical and experimental modes. So we updated the linear models thanks to material and geometrical parameters, often unknown because of the complexity of the structures and materials. The numerically optimized values have been verified thanks to the measures we made on the masonry components in situ and in laboratory. We are now working on non-linear models redistributing the strains. So we validate the damage threshold criteria which we use to compute the vulnerability curves of each defined structural type. Our actual results show a good correlation between experimental and numerical data, validating the final modeling simplifications and the global method. We now plan to use non-linear analysis in the critical zones in order to test reinforcement solutions.

Keywords: heritage structures, masonry numerical modeling, seismic vulnerability assessment, vibratory measure

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46 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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45 Electronic Raman Scattering Calibration for Quantitative Surface-Enhanced Raman Spectroscopy and Improved Biostatistical Analysis

Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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44 Separation of Lanthanides Ions from Mineral Waste with Functionalized Pillar[5]Arenes: Synthesis, Physicochemical Characterization and Molecular Dynamics Studies

Authors: Ariesny Vera, Rodrigo Montecinos

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The rare-earth elements (REEs) or rare-earth metals (REMs), correspond to seventeen chemical elements composed by the fifteen lanthanoids, as well as scandium and yttrium. Lanthanoids corresponds to lanthanum and the f-block elements, from cerium to lutetium. Scandium and yttrium are considered rare-earth elements because they have ionic radii similar to the lighter f-block elements. These elements were called rare earths because they are simply more difficult to extract and separate individually than the most metals and, generally, they do not accumulate in minerals, they are rarely found in easily mined ores and are often unfavorably distributed in common ores/minerals. REEs show unique chemical and physical properties, in comparison to the other metals in the periodic table. Nowadays, these physicochemical properties are utilized in a wide range of synthetic, catalytic, electronic, medicinal, and military applications. Because of their applications, the global demand for rare earth metals is becoming progressively more important in the transition to a self-sustaining society and greener economy. However, due to the difficult separation between lanthanoid ions, the high cost and pollution of these processes, the scientists search the development of a method that combines selectivity and quantitative separation of lanthanoids from the leaching liquor, while being more economical and environmentally friendly processes. This motivation has favored the design and development of more efficient and environmentally friendly cation extractors with the incorporation of compounds as ionic liquids, membrane inclusion polymers (PIM) and supramolecular systems. Supramolecular chemistry focuses on the development of host-guest systems, in which a host molecule can recognize and bind a certain guest molecule or ion. Normally, the formation of a host-guest complex involves non-covalent interactions Additionally, host-guest interactions can be influenced among others effects by the structural nature of host and guests. The different macrocyclic hosts for lanthanoid species that have been studied are crown ethers, cyclodextrins, cucurbituryls, calixarenes and pillararenes.Among all the factors that can influence and affect lanthanoid (III) coordination, perhaps the most basic of them is the systematic control using macrocyclic substituents that promote a selective coordination. In this sense, macrocycles pillar[n]arenes (P[n]As) present a relatively easy functionalization and they have more π-rich cavity than other host molecules. This gives to P[n]As a negative electrostatic potential in the cavity which would be responsible for the selectivity of these compounds towards cations. Furthermore, the cavity size, the linker, and the functional groups of the polar headgroups could be modified in order to control the association of lanthanoid cations. In this sense, different P[n]As systems, specifically derivatives of the pentamer P[5]A functionalized with amide, amine, phosphate and sulfate derivatives, have been designed in terms of experimental synthesis and molecular dynamics, and the interaction between these P[5]As and some lanthanoid ions such as La³+, Eu³+ and Lu³+ has been studied by physicochemical characterization by 1H-NMR, ITC and fluorescence in the case of Eu³+ systems. The molecular dynamics study of these systems was developed in hexane as solvent, also taking into account the lanthanoid ions mentioned above, and the respective comparison studies between the different ions.

Keywords: lanthanoids, macrocycles, pillar[n]arenes, rare-earth metal extraction, supramolecular chemistry, supramolecular complexes.

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