Search results for: Morgan R. Heikal

Authors: Leo Laine, Morgan Johansson

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To meet the civilizations future needs for safe living and low environmental footprint, the engineers designing the complex systems of tomorrow will need efficient ways to model and optimize these systems for their intended purpose. For example, a civil defence shelter and its subsystem components needs to withstand, e.g. airblast and ground shock from decided design level explosion which detonates with a certain distance from the structure. In addition, the complex civil defence shelter needs to have functioning air filter systems to protect from toxic gases and provide clean air, clean water, heat, and electricity needs to also be available through shock and vibration safe fixtures and connections. Similar complex building systems can be found in any concentrated living or office area. In this paper, the authors use a multidomain modelling language called Modelica to model a concrete wall as a single degree of freedom (SDOF) system with elastoplastic properties with the implemented option of plastic hardening. The elastoplastic model was developed and implemented in the open source tool OpenModelica. The simulation model was tested on the case with a transient equivalent reflected pressure time history representing an airblast from 100 kg TNT detonating 15 meters from the wall. The concrete wall is approximately regarded as a concrete strip of 1.0 m width. This load represents a realistic threat on any building in a city like area. The OpenModelica model results were compared with an Excel implementation of a SDOF model with an elastic-plastic spring using simple fixed timestep central difference solver. The structural displacement results agreed very well with each other when it comes to plastic displacement magnitude, elastic oscillation displacement, and response times.

Keywords: airblast from explosives, elastoplastic spring model, Modelica modelling language, SDOF, structural response of concrete structure

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Authors: Fredrick Olatunji Ajegbomogun, Bello Modinat Morenikeji, Okorie Nancy Chituru

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Electronic information resources are highly relevant to students' academic and research needs but are grossly underutilized, despite the institutional commitment to making them available. The under-utilisation of these resources could be attributed to a low level of study behaviour coupled with a low level of computer self-efficacy. This study assessed computer self-efficacy, study behaviour, and the use of electronic information resources by students in selected polytechnics in Ogun State. A simple random sampling technique using Krejcie and Morgan's (1970) Table was used to select 370 respondents for the study. A structured questionnaire was used to collect data on respondents. Data were analysed using frequency counts, percentages, mean, standard deviation, Pearson Product Moment Correlation (PPMC) and multiple regression analysis. Results reveal that the internet (= 1.94), YouTube (= 1.74), and search engines (= 1.72) were the common information resources available to the students, while the Internet (= 4.22) is the most utilized resource. Major reasons for using electronic information resources were to source materials and information (= 3.30), for research (= 3.25), and to augment class notes (= 2.90). The majority (91.0%) of the respondents have a high level of computer self-efficacy in the use of electronic information resources through selecting from screen menus (= 3.12), using data files ( = 3.10), and efficient use of computers (= 3.06). Good preparation for tests (= 3.27), examinations (= 3.26), and organization of tutorials (= 3.11) are the common study behaviours of the respondents. Overall, 93.8% have good study behaviour. Inadequate computer facilities to access information (= 3.23), and poor internet access (= 2.87) were the major challenges confronting students’ use of electronic information resources. According to the PPMC results, study behavior (r = 0.280) and computer self-efficacy (r = 0.304) have significant (p 0.05) relationships with the use of electronic information resources. Regression results reveal that self-efficacy (=0.214) and study behavior (=0.122) positively (p 0.05) influenced students' use of electronic information resources. The study concluded that students' use of electronic information resources depends on the purpose, their computer self-efficacy, and their study behaviour. Therefore, the study recommended that the management should encourage the students to improve their study habits and computer skills, as this will enhance their continuous and more effective utilization of electronic information resources.

Keywords: computer self-efficacy, study behaviour, electronic information resources, polytechnics, Nigeria

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Authors: Suraj Mehrotra

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The stock market is a volatile, bustling marketplace that is a cornerstone of economics. It defines whether companies are successful or in spiral. A thorough understanding of it is important - many companies have whole divisions dedicated to analysis of both their stock and of rivaling companies. Linking the world of finance and artificial intelligence (AI), especially the stock market, has been a relatively recent development. Predicting how stocks will do considering all external factors and previous data has always been a human task. With the help of AI, however, machine learning models can help us make more complete predictions in financial trends. Taking a look at the stock market specifically, predicting the open, closing, high, and low prices for the next day is very hard to do. Machine learning makes this task a lot easier. A model that builds upon itself that takes in external factors as weights can predict trends far into the future. When used effectively, new doors can be opened up in the business and finance world, and companies can make better and more complete decisions. This paper explores the various techniques used in the prediction of stock prices, from traditional statistical methods to deep learning and neural networks based approaches, among other methods. It provides a detailed analysis of the techniques and also explores the challenges in predictive analysis. For the accuracy of the testing set, taking a look at four different models - linear regression, neural network, decision tree, and naïve Bayes - on the different stocks, Apple, Google, Tesla, Amazon, United Healthcare, Exxon Mobil, J.P. Morgan & Chase, and Johnson & Johnson, the naïve Bayes model and linear regression models worked best. For the testing set, the naïve Bayes model had the highest accuracy along with the linear regression model, followed by the neural network model and then the decision tree model. The training set had similar results except for the fact that the decision tree model was perfect with complete accuracy in its predictions, which makes sense. This means that the decision tree model likely overfitted the training set when used for the testing set.

Keywords: machine learning, testing set, artificial intelligence, stock analysis

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Authors: Pakinee Pooprasert, Wanxin Wang, Tina Parmar, Dana Ahnood, Tafadzwa Young-Zvandasara, James Morgan

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Homelessness has been shown to be correlated to poor health outcomes, including increased visual health morbidity. Despite this, there are relatively few studies regarding visual health in the homeless population, especially in the UK. This research aims to investigate visual disability and access barriers prevalent in the homeless population in Cardiff, South Wales. Data was collected from 100 homeless participants in three different shelters. Visual outcomes included near and distance visual acuity as well as non-cycloplegic refraction. Qualitative data was collected via a questionnaire and included socio-demographic profile, ocular history, subjective visual acuity and level of access to healthcare facilities. Based on the participants’ presenting visual acuity, the total prevalence of myopia and hyperopia was 17.0% and 19.0% respectively based on spherical equivalent from the eye with the greatest absolute value. The prevalence of astigmatism was 8.0%. The mean absolute spherical equivalent was 0.841D and 0.853D for right and left eye respectively. The number of participants with sight loss (as defined by VA= 6/12-6/60 in the better-seeing eye) was 27.0% in comparison to 0.89% and 1.1% in the general Cardiff and Wales population respectively (p-value is < 0.05). Additionally, 1.0% of the homeless subjects were registered blind (VA less than 3/60), in comparison to 0.17% for the national consensus after age standardization. Most participants had good knowledge regarding access to prescription glasses and eye examination services. Despite this, 85.0% never had their eyes examined by a doctor and 73.0% had their last optometrist appointment in more than 5 years. These findings suggested that there was a significant disparity in ocular health, including visual acuity and refractive error amongst the homeless in comparison to the general population. Further, the homeless were less likely to receive the same level of support and continued care in the community due to access barriers. These included a number of socio-economic factors such as travel expenses and regional availability of services, as well as administrative shortcomings. In conclusion, this research demonstrated unmet visual health needs within the homeless, and that inclusive policy changes may need to be implemented for better healthcare outcomes within this marginalized community.

Keywords: homelessness, refractive error, visual disability, Wales

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Authors: Mark Morgan, Christine Li, Shuangyu Xu, Jenny McCarty

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The National Wild and Scenic Rivers System was created by the U.S. Congress in 1968 (Public Law 90-542; 16 U.S.C. 1271 et seq.) to preserve outstanding natural, cultural, and recreational values of some U.S. rivers in a free-flowing condition for the enjoyment of present and future generations. This Act is notable for safeguarding the special character of these rivers while supporting management action that encourages public participation for co-creating river protection goals and strategies. This is not an easy task. To meet the challenges of modern ecosystem management, federal resource agencies must address many legal, environmental, economic, political, and social issues. The U.S. Forest Service manages a 44-mile section of the Eleven Point National Scenic River (EPR) in southern Missouri, mainly for outdoor recreation purposes. About half of the acreage is in private lands, while the remainder flows through the Mark Twain National Forest. Private land along the river is managed by scenic easements to ensure protection of scenic values and natural resources, without public access. A portion of the EPR lies adjacent to a 16,500-acre tract known as the Irish Wilderness. The spring-fed river has steep bluffs, deep pools, clear water, and a slow current, making it an ideal setting for outdoor enthusiasts. A 10-month visitor study was conducted at five access points along the EPR during 2019 so the US Forest Service could update their river management plan. A mail-back survey was administered to 560 on-site visitors, yielding a response rate of 53%. Although different types of visitors use the EPR, boating and fishing were the predominant forms of outdoor recreation. Some river use was from locals, but other visitors came from farther away. Formulating unbiased policies for outdoor recreation is difficult because managers must assign relative values to recreational activities and travel distance. Because policymaking is a subjective process, management decisions can affect user groups in different ways (i.e., boaters vs. fishers; proximate vs. distal visitors), as seen through a GIS analysis.

Keywords: activity selection, forest recreation, policy, travel distance

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Authors: Dumont Maxime, Correia Carlos, Sauvage Jean-François, Schwartz Noah, Gray Morgan

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Context: The concept of the segmented telescope is unavoidable to build extremely large telescopes (ELT) in the quest for spatial resolution, but it also allows one to fit a large telescope within a reduced volume of space (JWST) or into an even smaller volume (Standard Cubesat). Cubesats have tight constraints on the computational burden available and the small payload volume allowed. At the same time, they undergo thermal gradients leading to large and evolving optical aberrations. The pupil segmentation comes nevertheless with an obvious difficulty: to co-phase the different segments. The CubeSat constraints prevent the use of a dedicated wavefront sensor (WFS), making the focal-plane images acquired by the science detector the most practical alternative. Yet, one of the challenges for the wavefront sensing is the non-linearity between the image intensity and the phase aberrations. Plus, for Earth observation, the object is unknown and unrepeatable. Recently, several studies have suggested Neural Networks (NN) for wavefront sensing; especially convolutional NN, which are well known for being non-linear and image-friendly problem solvers. Aims: We study in this paper the prospect of using NN to measure the phasing aberrations of a segmented pupil from the focal-plane image directly without a dedicated wavefront sensing. Methods: In our application, we take the case of a deployable telescope fitting in a CubeSat for Earth observations which triples the aperture size (compared to the 10cm CubeSat standard) and therefore triples the angular resolution capacity. In order to reach the diffraction-limited regime in the visible wavelength, typically, a wavefront error below lambda/50 is required. The telescope focal-plane detector, used for imaging, will be used as a wavefront-sensor. In this work, we study a point source, i.e. the Point Spread Function [PSF] of the optical system as an input of a VGG-net neural network, an architecture designed for image regression/classification. Results: This approach shows some promising results (about 2nm RMS, which is sub lambda/50 of residual WFE with 40-100nm RMS of input WFE) using a relatively fast computational time less than 30 ms which translates a small computation burder. These results allow one further study for higher aberrations and noise.

Keywords: wavefront sensing, deep learning, deployable telescope, space telescope

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Authors: Stella Laletas, Andrea Reupert, Melinda Goodyear, Bradley Morgan

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Background: Many people with a mental illness have young children. Research has shown that early childhood is a particularly vulnerable time for children whose parents have a mental illness. Moreover, repeated research has demonstrated the effectiveness of a multiagency approach to family focused practice for improving parental functioning and preventing adverse outcomes in children whose parents have a mental illness, particularly in the early years of a child’s life. However, there is a paucity of professional development resources for professionals who work with families where a parent has a mental illness and has young children. Significance of the study: This study will make a contribution to addressing knowledge gaps around resource development and workforce needs for early childhood and mental health professionals working with young children where a parent has a mental illness. Objective: This presentation describes a newly developed resource, 'Pathways of Care', specifically designed for early childhood educators and mental health workers, alongside pilot evaluation data regarding its effectiveness. ‘Pathways of Care’ aims to promote collaborative practice and present early identification and referral processes for workers in this sector. The resource was developed by the Children of Parents with a Mental Illness (COPMI) National Initiative which is funded by the Australian Government. Method: Using a mixed method design, the effectiveness of the training resource is also presented. Fifteen workers completed the Family Focus Mental Health Practice Questionnaire pre and post using the resource, to measure confidence and practice change; semi-structured interviews were also conducted with eight of these same workers to further explore the utility of the resource. Findings: The findings indicated the resource was effective in increasing knowledge and confidence, particularly for new and/or inexperienced staff. Examples of how the resource was used in practice by various professions emerged from the interview data. Conclusions: Collaborative practice, early identification and intervention in early childhood can potentially play a key role in altering the life trajectory of children who are at risk. This information has important implications for workforce development and staff training in both the early childhood and mental health sectors. Implications for policy and future research are discussed.

Keywords: parents with mental ilnesses, early intervention, evaluation, preschool children

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Authors: Morgan Cheng, Wilson Ho, Max Yiu, Dragon Tsui, Wylog Wong, Richard Kwan, K. C. Lam, Hannah Lo, C. L. Wong

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Hong Kong has been known worldwide for its ability to thrive under trying circumstances. The 7.5 million residents of this mature and busy metropolis are living in a primarily high-rise city whereby development and renewal of the cityscape are taking place unceasingly. Hong Kong residents are therefore affected by the virtually continuous and numerous construction activities. In 2020, the Hong Kong environmental protection department (EPD) completed a feasibility study on managing construction noise, including those associated with the renovation of domestic premises. Part of the study was the review of management and control of construction noise in other metropolitan cities globally. As far as the authors are aware of, such worldwide and extensive review of best practices on construction noise control has not been conducted for over 20 years. In order to benefit from international best practices, the extensive review is to identify possible areas for improvement in Hong Kong. The consultant of the study first referred to the United Nations Report ‘The World’s Cities in 2016’ and examined the top 100 cities therein. The 20 most suitable cities were then chosen for further review. Upon screening of each of these 20 cities, 12 cities with the more relevant management practices were selected for further scrutiny. These 12 cities were: Asia – Tokyo, Seoul, Taipei, Guangzhou, Singapore; Europe – City of Westminster (London), Berlin; North America – Toronto, New York City, San Francisco; Oceania – Sydney, Melbourne. Afterwards, three cities, namely Sydney, City of Westminster, and New York City, were selected for in-depth review. These cities were chosen primarily because of the maturity, success, and effectiveness of their construction noise management and control measures, as well as their similarity to Hong Kong in key and selected aspects. One of the more important findings of the review is the usefulness of early focus, with the aim of designing the noise issues away wherever practicable. The consultant examined the similar yet different construction noise early focus mechanisms of the three cities. This paper describes this landmark worldwide and extensive review of international best practices on construction noise management and control. The methodology, approach, and key findings are presented to give readers a succinct yet comprehensive view. The authors shared the findings with the acoustics professionals worldwide with the hope of global advancement of more mature construction noise management while welcoming sustainable development and construction.

Keywords: construction noise, international best practices, noise control, noise management

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Authors: Morgan Dombroski, Alexis Hartman

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Purpose: The present study aimed to explore factors related to overtraining within a female collegiate sample by analyzing the aftereffects of overtraining on athletes' physical and emotional well-being. Methods: 51 female collegiate athletes participated in a de-identified survey to assess factors related to overtraining. All survey questions were derived from the Recovery-Stress Questionnaire. Descriptive and bivariate correlations were conducted to test for significant factors related to the athletes' physical and emotional well-being relating to sports engagement. Results: Descriptive statistics indicated: 80.4% of athletes reported feeling tired from sport-related work, 72.5% reported parts of their body were aching, 47.1% reported feeling emotionally drained, and 37.3% reported feeling burnt out by sport. These findings were consistent with bivariate correlations, which yielded statistically significant findings between physical fatigue and emotional distress. Discussion: In a general sense, athletes increase their training to maximize their performance. The current study aimed to analyze how this training process can result in overtraining of female collegiate athletes, which in turn may negatively impact their physical and emotional functioning. Overtraining syndrome can occur as a maladaptive response to excessive exercise and inappropriate rest caused by systemic inflammation, which negatively affects the central nervous system. The physical manifestations of overtraining can then lead to depressed mood, fatigue, and neurohormonal changes in athletes. To remain competitive and high performing in sports, athletes partaking in excessive training can result in overtraining syndrome, athlete burnout, and compulsive exercise. Additionally, overtrained athletes were defined by displaying high levels of perfectionism, maladaptive coping, and training distress. The current study supported these findings, which yielded a strong correlation between physical and emotional functioning in the context of overtraining in sports. All in all, the environment revolving around sports and the intensity of training can be extremely stressful for athletes. There is a need to monitor athletes’ subjective responses to training, which will allow for early identification of at-risk athletes giving clinicians various opportunities to reduce the negative consequences of overtraining. By better understanding symptoms of emotional and physical fatigue, collegiate sports can become more aware of overtraining symptoms to prevent further detriment to female athletes' overall well-being.

Keywords: burnout, emotionally drained, overtraining, performance, well-being

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Authors: Nada R. Abuknesha, John P. Morgan, Andrew J. Searle

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Information regarding post-mortem interval (PMI) in criminal investigations is vital to establish a time frame when reconstructing events. PMI is defined as the time period that has elapsed between the occurrence of death and the discovery of the corpse. Adipocere, commonly referred to as ‘grave-wax’, is formed when post-mortem adipose tissue is converted into a solid material that is heavily comprised of fatty acids. Adipocere is of interest to forensic anthropologists, as its formation is able to slow down the decomposition process. Therefore, analysing the changes in the patterns of fatty acids during the early decomposition process may be able to estimate the period of burial, and hence the PMI. The current study concerned the investigation of the fatty acid composition and patterns in buried pig fat tissue. This was in an attempt to determine whether particular patterns of fatty acid composition can be shown to be associated with the duration of the burial, and hence may be used to estimate PMI. The use of adipose tissue from the abdominal region of domestic pigs (Sus-scrofa), was used to model the human decomposition process. 17 x 20cm piece of pork belly was buried in a shallow artificial grave, and weekly samples (n=3) from the buried pig fat tissue were collected over an 11-week period. Marker fatty acids: palmitic (C16:0), oleic (C18:1n-9) and linoleic (C18:2n-6) acid were extracted from the buried pig fat tissue and analysed as fatty acid methyl esters using the gas chromatography system. Levels of the marker fatty acids were quantified from their respective standards. The concentrations of C16:0 (69.2 mg/mL) and C18:1n-9 (44.3 mg/mL) from time zero exhibited significant fluctuations during the burial period. Levels rose (116 and 60.2 mg/mL, respectively) and fell starting from the second week to reach 19.3 and 18.3 mg/mL, respectively at week 6. Levels showed another increase at week 9 (66.3 and 44.1 mg/mL, respectively) followed by gradual decrease at week 10 (20.4 and 18.5 mg/mL, respectively). A sharp increase was observed in the final week (131.2 and 61.1 mg/mL, respectively). Conversely, the levels of C18:2n-6 remained more or less constant throughout the study. In addition to fluctuations in the concentrations, several new fatty acids appeared in the latter weeks. Other fatty acids which were detectable in the time zero sample, were lost in the latter weeks. There are several probable opportunities to utilise fatty acid analysis as a basic technique for approximating PMI: the quantification of marker fatty acids and the detection of selected fatty acids that either disappear or appear during the burial period. This pilot study indicates that this may be a potential semi-quantitative methodology for determining the PMI. Ideally, the analysis of particular fatty acid patterns in the early stages of decomposition could be an additional tool to the already available techniques or methods in improving the overall processes in estimating PMI of a corpse.

Keywords: adipocere, fatty acids, gas chromatography, post-mortem interval

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Authors: Gerald Amatre, Julius Bunny Lejju, Morgan Andama

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Despite several interventions, jigger flea infestations continue to be reported in the Busoga sub-region in Eastern Uganda. The purpose of this study was to identify factors that expose the indigenous people to jigger flea infestations and evaluate the effectiveness of any indigenous materials used in flea control by the affected communities. Flea compositions in residences were described, factors associated with flea infestation and indigenous materials used in flea control were evaluated. Field surveys were conducted in the affected communities after obtaining preliminary information on jigger infestation from the offices of the District Health Inspectors to identify the affected villages and households. Informed consent was then sought from the local authorities and household heads to conduct the study. Focus group discussions were conducted with key district informants, namely, the District Health Inspectors, District Entomologists and representatives from the District Health Office. A GPS coordinate was taken at central point at every household enrolled. Fleas were trapped inside residences using Kilonzo traps. A Kilonzo Trap comprised a shallow pan, about three centimetres deep, filled to the brim with water. The edges of the pan were smeared with Vaseline to prevent fleas from crawling out. Traps were placed in the evening and checked every morning the following day. The trapped fleas were collected in labelled vials filled with 70% aqueous ethanol and taken to the laboratory for identification. Socio-economic and environmental data were collected. The results indicate that the commonest flea trapped in the residences was the cat flea (Ctenocephalides felis) (50%), followed by Jigger flea (Tunga penetrans) (46%) and rat flea (Xenopsylla Cheopis) (4%), respectively. The average size of residences was seven squire metres with a mean of six occupants. The residences were generally untidy; with loose dusty floors and the brick walls were not plastered. The majority of the jigger affected households were headed by peasants (86.7%) and artisans (13.3%). The household heads mainly stopped at primary school level (80%) and few at secondary school level (20%). The jigger affected households were mainly headed by peasants of low socioeconomic status. The affected community members use soil-cow dung-ash mixture to smear floors of residences as the only measure to control fleas. This method was found to be ineffective in controlling the insects. The study recommends that home improvement campaigns be continued in the affected communities to improve sanitation and hygiene in residences as one of the interventions to combat flea infestations. Other cheap, available and effective means should be identified to curb jigger flea infestations.

Keywords: cow dung-soil-ash mixture, infestations, jigger flea, Tunga penetrans

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Authors: Morgan Johansson, Joosef Leppanen, Mathias Flansbjer, Fabio Lozano, Josef Makdesi

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Concrete is commonly used for protective structures and how impact loading affects different types of concrete structures is an important issue. Often the knowledge gained from static loading is also used in the design of impulse loaded structures. A large plastic deformation capacity is essential to obtain a large energy absorption in an impulse loaded structure. However, the structural response of an impact loaded concrete beam may be very different compared to a statically loaded beam. Consequently, the plastic deformation capacity and failure modes of the concrete structure can be different when subjected to dynamic loads; and hence it is not sure that the observations obtained from static loading are also valid for dynamic loading. The aim of this paper is to investigate the residual plastic deformation capacity in reinforced concrete beams subjected to drop weight impact tests. A test-series consisting of 18 simply supported beams (0.1 x 0.1 x 1.18 m, ρs = 0.7%) with a span length of 1.0 m and subjected to a point load in the beam mid-point, was carried out. 2x6 beams were first subjected to drop weight impact tests, and thereafter statically tested until failure. The drop in weight had a mass of 10 kg and was dropped from 2.5 m or 5.0 m. During the impact tests, a high-speed camera was used with 5 000 fps and for the static tests, a camera was used with 0.5 fps. Digital image correlation (DIC) analyses were conducted and from these the velocities of the beam and the drop weight, as well as the deformations and crack propagation of the beam, were effectively measured. Additionally, for the static tests, the applied load and midspan deformation were measured. The load-deformation relations for the beams subjected to an impact load were compared with 6 reference beams that were subjected to static loading only. The crack pattern obtained were compared using DIC, and it was concluded that the resulting crack formation depended much on the test method used. For the static tests, only bending cracks occurred. For the impact loaded beams, though, distinctive diagonal shear cracks also formed below the zone of impact and less wide shear cracks were observed in the region half-way to the support. Furthermore, due to wave propagation effects, bending cracks developed in the upper part of the beam during initial loading. The results showed that the plastic deformation capacity increased for beams subjected to drop weight impact tests from a high drop height of 5.0 m. For beams subjected to an impact from a low drop height of 2.5 m, though, the plastic deformation capacity was in the same order of magnitude as for the statically loaded reference beams. The beams tested were designed to fail due to bending when subjected to a static load. However, for the impact tested beams, one beam exhibited a shear failure at a significantly reduced load level when it was tested statically; indicating that there might be a risk of reduced residual load capacity for impact loaded structures.

Keywords: digital image correlation (DIC), drop weight impact, experiments, plastic deformation capacity, reinforced concrete

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Naod Mekonnen Anega

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The very objective of this paper was to empirically identify technology tailored determinants to the adoption and adoption intensity (extent of use) of agricultural water management technologies in Meda Welabu Woreda, Oromia regional state, Ethiopia. Meda Welabu Woreda which is one of the administrative Woredas of the Oromia regional state was selected purposively as this Woreda is one of the Woredas in the region where small scale irrigation practices and the use of agricultural water management technologies can be found among smallholders. Using the existence water management practices (use of water management technologies) and land use pattern as a criterion Genale Mekchira Kebele is selected to undergo the study. A total of 200 smallholders were selected from the Kebele using the technique developed by Krejeie and Morgan. The study employed the Logit and Tobit models to estimate and identify the economic, social, geographical, household, institutional, psychological, technological factors that determine adoption and adoption intensity of water management technologies. The study revealed that while 55 of the sampled households are adopters of agricultural water management technology the rest 140 were non adopters of the technologies. Among the adopters included in the sample 97% are using river diversion technology (traditional) with traditional canal while the rest 7% percent are using pond with treadle pump technology. The Logit estimation reveled that while adoption of river diversion is positively and significantly affected by membership to local institutions, active labor force, income, access to credit and land ownership, adoption of treadle pump technology is positively and significantly affected by family size, education level, access to credit, extension contact, income, access to market, and slope. The Logit estimation also revealed that whereas, group action requirement, distance to farm, and size of active labor force negative and significantly influenced adoption of river diversion, age and perception has negatively and significantly influenced adoption decision of treadle pump technology. On the other hand, the Tobit estimation reveled that while adoption intensity (extent of use) of agricultural water management is positively and significantly affected by education, credit, and extension contact, access to credit, access to market and income. This study revealed that technology tailored study on adoption of Agricultural water management technologies (AWMTs) should be considered to indentify and scale up best agricultural water management practices. In fact, in countries like Ethiopia, where there is difference in social, economic, cultural, environmental and agro ecological conditions even within the same Kebele technology tailored study that fit the condition of each Kebele would help to identify and scale up best practices in agricultural water management.

Keywords: water management technology, adoption, adoption intensity, smallholders, technology tailored approach

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Authors: Te Kīpa Kēpa B. Morgan, Oliver W. Mcmillan, Dylan N. Taute, Tumanako N. Fa'aui

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Epistemologies are ways of knowing. Indigenous Peoples are aware that they do not perceive and experience the world in the same way as others. So it is important when empowering Indigenous epistemologies, such as that of the New Zealand Māori, to also be able to represent a scientific understanding within the same analysis. A geothermal development assessment tool has been developed by adapting the Mauri Model Decision Making Framework. Mauri is a metric that is capable of representing the change in the life-supporting capacity of things and collections of things. The Mauri Model is a method of grouping mauri indicators as dimension averages in order to allow holistic assessment and also to conduct sensitivity analyses for the effect of worldview bias. R-shiny is the coding platform used for this Vision Mātauranga research which has created an expert decision support tool (DST) that combines a stakeholder assessment of worldview bias with an impact assessment of mauri-based indicators to determine the sustainability of proposed geothermal development. The initial intention was to develop guidelines for quantifying mātauranga Māori impacts related to geothermal resources. To do this, three typical scenarios were considered: a resource owner wishing to assess the potential for new geothermal development; another party wishing to assess the environmental and cultural impacts of the proposed development; an assessment that focuses on the holistic sustainability of the resource, including its surface features. Indicator sets and measurement thresholds were developed that are considered necessary considerations for each assessment context and these have been grouped to represent four mauri dimensions that mirror the four well-being criteria used for resource management in Aotearoa, New Zealand. Two case studies have been conducted to test the DST suitability for quantifying mātauranga Māori and other biophysical factors related to a geothermal system. This involved estimating mauri0meter values for physical features such as temperature, flow rate, frequency, colour, and developing indicators to also quantify qualitative observations about the geothermal system made by Māori. A retrospective analysis has then been conducted to verify different understandings of the geothermal system. The case studies found that the expert DST is useful for geothermal development assessment, especially where hapū (indigenous sub-tribal grouping) are conflicted regarding the benefits and disadvantages of their’ and others’ geothermal developments. These results have been supplemented with evaluations for the cumulative impacts of geothermal developments experienced by different parties using integration techniques applied to the time history curve of the expert DST worldview bias weighted plotted against the mauri0meter score. Cumulative impacts represent the change in resilience or potential of geothermal systems, which directly assists with the holistic interpretation of change from an Indigenous Peoples’ perspective.

Keywords: decision support tool, holistic geothermal assessment, indigenous knowledge, mauri model decision-making framework

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Authors: BoSheng Liu

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The research goal is to re-image a locally-sourced waste product as abuilding material. The author aims to contribute to the compressed stabilized earth block (CSEB) by investigating the promising role of dredged material as an alternative building ingredient in the production of bricks and tiles. Dredged material comes from the sediment deposited near the shore or downstream, where the water current velocity decreases. This sediment needs to be dredged to provide water transportation; thus, there are mounds of the dredged material stored at bay. It is the interest of this research to reduce the filtered un-organic soil in the production of CSEB and replace it with locally dredged material from the Atchafalaya River in Morgan City, Louisiana. Technology and mechanical innovations have evolved the traditional adobe production method, which mixes the soil and natural fiber into molded bricks, into chemically stabilized CSEB made by compressing the clay mixture and stabilizer in a compression chamber with particular loads. In the case of dredged material CSEB (DM-CSEB), cement plays an essential role as the bending agent contributing to the unit strength while sustaining the filtered un-organic soil. Each DM-CSEB unit is made in a compression chamber with 580 PSI (i.e., 4 MPa) force. The research studied the cement content from 5% to 10% along with the range of dredged material mixtures, which differed from 20% to 80%. The material mixture content affected the DM-CSEB's strength and workability during and after its compression. Results indicated two optimal workabilities of the mixture: 27% fine clay content and 63% dredged material with 10% cement, or 28% fine clay content, and 67% dredged material with 5% cement. The final product of DM-CSEB emitted between 10 to 13 times fewer carbon emissions compared to the conventional fired masonry structure. DM-CSEB satisfied the strength requirement given by the ASTM C62 and ASTM C34 standards for construction material. One of the final evaluations tested and validated the material performance by designing and constructing an architectural, conical tile-vault prototype that was 28" by 40" by 24." The vault utilized a computational form-finding approach to generate the form's geometry, which optimized the correlation between the vault geometry and structural load distribution. A series of scaffolding was deployed to create the framework for the tile-vault construction. The final tile-vault structure was made from 2 layers of DM-CSEB tiles jointed by mortar, and the construction of the structure used over 110 tiles. The tile-vault prototype was capable of carrying over 400 lbs of live loads, which further demonstrated the dredged material feasibility as a construction material. The presented case study of Dredged Material Compressed Stabilized Earth Block (DM-CSEB) provides the first impression of dredged material in the clayey mixture process, structural performance, and construction practice. Overall, the approach of integrating dredged material in building material can be feasible, regionally sourced, cost-effective, and environment-friendly.

Keywords: dredged material, compressed stabilized earth block, tile-vault, regionally sourced, environment-friendly

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Authors: Sumedha Weerasekara, Morgan Miles, Mark Morrison, Branka Krivokapic-Skoko

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This paper is aimed at exploring the interrelationships among entrepreneurial ecosystem factors and entrepreneurial cognition in regional and metropolitan ecosystems. Entrepreneurial ecosystem factors examined include: culture, infrastructure, access to finance, informal networks, support services, access to universities, and the depth and breadth of the talent pool. Using a multivariate approach we explore the impact of these ecosystem factors or elements on entrepreneurial cognition. In doing so, the existing body of knowledge from the literature on entrepreneurial ecosystem and cognition have been blended to explore the relationship between entrepreneurial ecosystem factors and cognition in a way not hitherto investigated. The concept of the entrepreneurial ecosystem has received increased attention as governments, universities and communities have started to recognize the potential of integrated policies, structures, programs and processes that foster entrepreneurship activities by supporting innovation, productivity and employment growth. The notion of entrepreneurial ecosystems has evolved and grown with the advancement of theoretical research and empirical studies. Importance of incorporating external factors like culture, political environment, and the economic environment within a single framework will enhance the capacity of examining the whole systems functionality to better understand the interaction of the entrepreneurial actors and factors within a single framework. The literature on clusters underplays the role of entrepreneurs and entrepreneurial management in creating and co-creating organizations, markets, and supporting ecosystems. Entrepreneurs are only one actor following a limited set of roles and dependent upon many other factors to thrive. As a consequence, entrepreneurs and relevant authorities should be aware of the other actors and factors with which they engage and rely, and make strategic choices to achieve both self and also collective objectives. The study uses stratified random sampling method to collect survey data from 12 different regions in regional and metropolitan regions of NSW, Australia. A questionnaire was administered online among 512 Small and medium enterprise owners operating their business in selected 12 regions in NSW, Australia. Data were analyzed using descriptive analyzing techniques and partial least squares - structural equation modeling. The findings show that even though there is a significant relationship between each and every entrepreneurial ecosystem factors, there is a weak relationship between most entrepreneurial ecosystem factors and entrepreneurial cognition. In the metropolitan context, the availability of finance and informal networks have the largest impact on entrepreneurial cognition while culture, infrastructure, and support services having the smallest impact and the talent pool and universities having a moderate impact on entrepreneurial cognition. Interestingly, in a regional context, culture, availability of finance, and the talent pool have the highest impact on entrepreneurial cognition, while informal networks having the smallest impact and the remaining factors – infrastructure, universities, and support services have a moderate impact on entrepreneurial cognition. These findings suggest the need for a location-specific strategy for supporting the development of entrepreneurial cognition.

Keywords: academic achievement, colour response card, feedback

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Authors: Staci McGill, Morgan Hayes, Robert Coleman, Kimberly Tumlin

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The interaction and relationships between horses and humans have been shown to be positive for physical, mental, and emotional wellbeing, however equine spaces where these interactions occur do include some environmental risks. There are 1.7 million jobs associated with the equine industry in the United States in addition to recreational riders, owners, and volunteers who interact with horses for substantial amounts of time daily inside built structures. One specialized facility, an “indoor arena” is a semi-indoor structure used for exercising horses and exhibiting skills during competitive events. Typically, indoor arenas have a sand or sand mixture as the footing or surface over which the horse travels, and increasingly, silica sand is being recommended due to its durable nature. It was previously identified in a semi-qualitative survey that the majority of individuals using indoor arenas have environmental concerns with dust. 27% (90/333) of respondents reported respiratory issues or allergy-like symptoms while riding with 21.6% (71/329) of respondents reporting these issues while standing on the ground observing or teaching. Frequent headaches and/or lightheadedness was reported in 9.9% (33/333) of respondents while riding and in 4.3% 14/329 while on the ground. Horse respiratory health is also negatively impacted with 58% (194/333) of respondents indicating horses cough during or after time in the indoor arena. Instructors who spent time in indoor arenas self-reported more respiratory issues than those individuals who identified as smokers, highlighting the health relevance of understanding these unique structures. To further elucidate environmental concerns and self-reported health issues, 35 facility assessments were conducted in a cross-sectional sampling design in the states of Kentucky and Ohio (USA). Data, including air speeds, were collected in a grid fashion at 15 points within the indoor arenas and then mapped spatially using krigging in ARCGIS. From the spatial maps, standard variances were obtained and differences were analyzed using multivariant analysis of variances (MANOVA) and analysis of variances (ANOVA). There were no differences for the variance of the air speeds in the spaces for facility orientation, presence and type of roof ventilation, climate control systems, amount of openings, or use of fans. Variability of the air speeds in the indoor arenas was 0.25 or less. Further analysis yielded that average air speeds within the indoor arenas were lower than 100 ft/min (0.51 m/s) which is considered still air in other animal facilities. The lack of air movement means that dust clearance is reliant on particle size and weight rather than ventilation. While further work on respirable dust is necessary, this characterization of the semi-indoor environment where animals and humans interact indicates insufficient air flow to eliminate or reduce respiratory hazards. Finally, engineering solutions to address air movement deficiencies within indoor arenas or mitigate particulate matter are critical to ensuring exposures do not lead to adverse health outcomes for equine professionals, volunteers, participants, and horses within these spaces.

Keywords: equine, indoor arena, ventilation, particulate matter, respiratory health

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Authors: Carlos M. Parra, Matthew Sutherland, Ranjita Poudel

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Reduced mental-bandwidth related to low socioeconomic status (low-SES) might lead to impulsivity and risk-taking behavior, which poses as a major hurdle towards asset building (savings) behavior. Understanding the relationship between risk-related personality metrics as well as laboratory risk behavior and real-life savings behavior can help facilitate the development of effective asset building programs, which are vital for mitigating financial vulnerability and income inequality. As such, this study explored the relationship between personality metrics, laboratory behavior in a risky decision-making task and real-life asset building (savings) behaviors among individuals with low-SES from Miami, Florida (FL). Study participants (12 male, 15 female) included racially and ethnically diverse adults (mean age 41.22 ± 12.65 years), with incomplete higher education (18% had High School Diploma, 30% Associates, and 52% Some College), and low annual income (mean $13,872 ± $8020.43). Participants completed eight self-report surveys and played a widely used risky decision-making paradigm called the Balloon Analogue Risk Task (BART). Specifically, participants played three runs of BART (20 trials in each run; total 60 trials). In addition, asset building behavior data was collected for 24 participants who opened and used savings accounts and completed a 6-month savings program that involved monthly matches, and a final reward for completing the savings program without any interim withdrawals. Each participant’s total savings at the end of this program was the main asset building indicator considered. In addition, a new effective use of average pump bet (EUAPB) indicator was developed to characterize each participant’s ability to place winning bets. This indicator takes the ratio of each participant’s total BART earnings to average pump bet (APB) in all 60 trials. Our findings indicated that EUAPB explained more than a third of the variation in total savings among participants. Moreover, participants who managed to obtain BART earnings of at least 30 cents out of their APB, also tended to exhibit better asset building (savings) behavior. In particular, using this criterion to separate participants into high and low EUAPB groups, the nine participants with high EUAPB (mean BART earnings of 35.64 cents per APB) ended up with higher mean total savings ($255.11), while the 15 participants with low EUAPB (mean BART earnings of 22.50 cents per APB) obtained lower mean total savings ($40.01). All mean differences are statistically significant (2-tailed p  .0001) indicating that the relation between higher EUAPB and higher total savings is robust. Overall, these findings can help refine asset building interventions implemented by policy makers and practitioners interested in reducing financial vulnerability among low-SES population. Specifically, by helping identify individuals who are likely to readily take advantage of savings opportunities (such as matched savings programs) and avoiding the stipulation of unnecessary and expensive financial coaching programs to these individuals. This study was funded by J.P. Morgan Chase (JPMC) and carried out by scientists from Florida International University (FIU) in partnership with Catalyst Miami.

Keywords: balloon analogue risk task (BART), matched savings programs, asset building capability, low-SES participants

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Authors: Joshua Kaufman, Felix Tan, Morgan Monroe, Ayman Abouraddy

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Textiles and clothing have been a staple of human existence for millennia, yet the basic structure and functionality of textile fibers and yarns has remained unchanged. While color and appearance are essential characteristics of a textile, an advancement in the fabrication of yarns that allows for user-controlled dynamic changes to the color or appearance of a garment has been lacking. Touch-activated and photosensitive pigments have been used in textiles, but these technologies are passive and cannot be controlled by the user. The technology described here allows the owner to control both when and in what pattern the fabric color-change takes place. In addition, the manufacturing process is compatible with mass-producing the user-controlled, color-changing yarns. The yarn fabrication utilizes a fiber spinning system that can produce either monofilament or multifilament yarns. For products requiring a more robust fabric (backpacks, purses, upholstery, etc.), larger-diameter monofilament yarns with a coarser weave are suitable. Such yarns are produced using a thread-coater attachment to encapsulate a 38-40 AWG metal wire inside a polymer sheath impregnated with thermochromic pigment. Conversely, products such as shirts and pants requiring yarns that are more flexible and soft against the skin comprise multifilament yarns of much smaller-diameter individual fibers. Embedding a metal wire in a multifilament fiber spinning process has not been realized to date. This research has required collaboration with Hills, Inc., to design a liquid metal-injection system to be combined with fiber spinning. The new system injects molten tin into each of 19 filaments being spun simultaneously into a single yarn. The resulting yarn contains 19 filaments, each with a tin core surrounded by a polymer sheath impregnated with thermochromic pigment. The color change we demonstrate is distinct from garments containing LEDs that emit light in various colors. The pigment itself changes its optical absorption spectrum to appear a different color. The thermochromic color-change is induced by a temperature change in the inner metal wire within each filament when current is applied from a small battery pack. The temperature necessary to induce the color change is near body temperature and not noticeable by touch. The prototypes already developed either use a simple push button to activate the battery pack or are wirelessly activated via a smart-phone app over Wi-Fi. The app allows the user to choose from different activation patterns of stripes that appear in the fabric continuously. The power requirements are mitigated by a large hysteresis in the activation temperature of the pigment and the temperature at which there is full color return. This was made possible by a collaboration with Chameleon International to develop a new, customized pigment. This technology enables a never-before seen capability: user-controlled, dynamic color and pattern change in large-area woven and sewn textiles and fabrics with wide-ranging applications from clothing and accessories to furniture and fixed-installation housing and business décor. The ability to activate through Wi-Fi opens up possibilities for the textiles to be part of the ‘Internet of Things.’ Furthermore, this technology is scalable to mass-production levels for wide-scale market adoption.

Keywords: activation, appearance, color, manufacturing

Procedia PDF Downloads 258

Authors: Yaser Ghasemi Aryan, Firoozeh Moghiminejad, Mohammadreza Shahraki

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Background: The cooperative institution is considered the first and most essential pillar of strengthening social capital, whose sustainability is the main guarantee of survival and continued participation of local communities in natural resource management projects. The Village Development Group and the Microcredit Fund are two important social and economic institutions in the implementation of the International Project for the Restoration of Degraded Forest Lands (RFLDL) in Sarayan City, South Khorasan Province, which has learned positive lessons from the participation of the beneficiaries in the implementation. They have brought more effective projects to deal with desertification. However, the low activity or liquidation of some of these institutions has become one of the important challenges and concerns of project executive experts. The current research was carried out with the aim of explaining the main components of the instability of these institutions. Materials and Methods: This research is descriptive-analytical in terms of method, practical in terms of purpose, and the method of collecting information is two documentary and survey methods. The statistical population of the research included all the members of the village development groups and microcredit funds in the target villages of the RFLDL project of Sarayan city, based on the Kochran formula and matching with the Karjesi and Morgan table. Net people were selected as a statistical sample. After confirming the validity of the expert's opinions, the reliability of the questionnaire was 0.83, which shows the appropriate reliability of the researcher-made questionnaire. Data analysis was done using SPSS software. Results: The results related to the extraction of obstacles to the stability of social and economic networks were classified and prioritized in the form of 5 groups of social-cultural, economic, administrative, educational-promotional and policy-management factors. Based on this, in the socio-cultural factors, the items ‘not paying attention to the structural characteristics and composition of groups’, ‘lack of commitment and moral responsibility in some members of the group,’ and ‘lack of a clear pattern for the preservation and survival of groups’, in the disciplinary factors, The items ‘Irregularity in holding group meetings’ and ‘Irregularity of members to participate in meetings’, in the economic factors of the items "small financial capital of the fund’, ‘the low amount of loans of the fund’ and ‘the fund's inability to conclude contracts and attract capital from other sources’, in the educational-promotional factors of the items ‘non-simultaneity of job training with the granting of loans to create jobs’ and ‘insufficient training for the effective use of loans and job creation’ and in the policy-management factors of the item ‘failure to provide government facilities for support From the funds, they had the highest priority. Conclusion: In general, the results of this research show that policy-management factors and social factors, especially the structure and composition of social and economic institutions, are the most important obstacles to their sustainability. Therefore, it is suggested to form cooperative institutions based on network analysis studies in order to achieve the appropriate composition of members.

Keywords: cooperative institution, social capital, network analysis, participation, Sarayan.

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 151