Search results for: individuals with mild intellectual disabilities

Authors: Deeksha Karunakar

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The gaming industry is one of the biggest industries in the world. Video games are interactive works of authorship that require the execution of a computer programme on specialized hardware but which also incorporate a wide variety of other artistic mediums, such as music, scripts, stories, video, paintings, and characters, into which the player takes an active role. Therefore, video games are not made as singular, simple works but rather as a collection of elements that, if they reach a certain level of originality and creativity, can each be copyrighted on their own. A video game is made up of a wide variety of parts, all of which combine to form the overall sensation that we, the players, have while playing. The entirety of the components is implemented in the form of software code, which is then translated into the game's user interface. Even while copyright protection is already in place for the coding of software, the work that is produced because of that coding can also be protected by copyright. This includes the game's storyline or narrative, its characters, and even elements of the code on their own. In each sector, there is a potential legal framework required, and the gaming industry also requires legal frameworks. This represents the importance of intellectual property laws in each sector. This paper will explore the beginnings of video games, the various aspects of game copyrights, and the approach of the courts, including examples of a few different instances. Although the creative arts have always been known to draw inspiration from and build upon the works of others, it has not always been simple to evaluate whether a game has been cloned. The video game business is experiencing growth as it has never seen before today. The majority of today's video games are both pieces of software and works of audio-visual art. Even though the existing legal framework does not have a clause specifically addressing video games, it is clear that there is a great many alternative means by which this protection can be granted. This paper will represent the importance of copyright and trademark laws in the gaming industry and its regulations with the help of relevant case laws via utilizing doctrinal methodology to support its findings. The aim of the paper is to make aware of the applicability of intellectual property laws in the gaming industry and how the justice system is evolving to adapt to such new industries. Furthermore, it will provide in-depth knowledge of their relationship with each other.

Keywords: copyright, DMCA, gaming industry, trademark, WIPO

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Authors: Rubina Jahan, Mohammad Zayeed Bin Alam, Sazzad Chowdhury, Sadia Chowdhury

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Access to mental health services in Bangladesh is a tale of urban privilege and rural struggle. Mental health services in the country are primarily centered in urban medical hospitals, with only 260 psychiatrists for a population of more than 162 million, while rural populations face far more severe and daunting challenges. In alignment with the World Health Organization's perspective on mental health as a basic human right and a crucial component for personal, community, and socioeconomic development; SAJIDA Foundation a value driven non-government organization in Bangladesh has introduced a Community Based Mental Health (CMHI) program to fill critical gaps in mental health care, providing accessible and affordable community-based services to protect and promote mental health, offering support for those grappling with mental health conditions. The CMHI programme is being implemented in 3 districts in Bangladesh, 2 of them are remote and most climate vulnerable areas targeting total 6,797 individual. The intervention plan involves a screening of all participants using a 10-point vulnerability assessment tool to identify vulnerable individuals. The assumption underlying this is that individuals assessed as vulnerable is primarily due to biological, psychological, social and economic factors and they are at an increased risk of developing common mental health issues. Those identified as vulnerable with high risk and emergency conditions will receive Mental Health First Aid (MHFA) and undergo further screening with GHQ-12 to be identified as cases and non-cases. The identified cases are then referred to community lay counsellors with basic training and knowledge in providing 4-6 sessions on problem solving or behavior activation. In situations where no improvement occurs post lay counselling or for individuals with severe mental health conditions, a referral process will be initiated, directing individuals to ensure appropriate mental health care. In our presentation, it will present the findings from 6-month pilot implementation focusing on the community-based screening versus outcome of the lay counseling session and barriers and facilitators of implementing community based mental health care in a resource constraint country like Bangladesh.

Keywords: community-based mental health, lay counseling, rural bangladesh, treatment gap

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Authors: Enoch Kudoahor, Nan Zheng

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We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.

Keywords: catalysis, endoperoxides, titanium dioxide, visible light

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Authors: Maomao Cao

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Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

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Authors: Lunthita M. Duthely, John T. Avella, John Ganapati Coleman

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For as many as one in three adolescents living in the United States, the adolescent years is a period of low well-being and mental health challenges—from depressive symptoms to mild to moderate psychological diagnoses. Longitudinal population health studies demonstrated that these challenges persist in young adulthood, and beyond. The positive psychology (PS) approach is a more preventative approach to well-being, which contrasts the traditional, deficits approach to curing mental illness. The research among adult populations formed the basis for PS studies among adolescents. The empirical evidence for the effectiveness of PS interventions exists for both adult and youth populations. Positive Psychology interventions target individuals’ strengths, such as hope and optimism, and positive emotions, such as gratitude. Positive psychology interventions such as increasing gratitude, proved effective in many outcomes among youth, including psychological, social, and academically-related outcomes. Although gratitude-inducing studies have been conducted for the past decade in the United States, few studies have been conducted among samples of urban youth, particularly youth of diverse cultural backgrounds. For nearly two decades, the secular practice of meditation has been tested among adults and more recently among youth, focused mostly among clinical samples. The field of Contemplative Sciences explores practices such as Hatha Yoga, Tai Chi, and Meditation, as preventative practices among children and adolescents. A more recent initiative is to explore Contemplative Practices in the school environment. Contemplative Practices yield a variety of positive outcomes, including academic, social, psychological, physiological, and neurological changes among children and adolescents. Again, few studies were conducted among adolescents of diverse cultural backgrounds. The purpose of this doctoral dissertation research study was to test a gratitude-meditation intervention among middle school students attending a public charter school, located in an urban region of Metropolitan Miami. The objective of this presentation is to summarize the challenges and success of bringing a positive psychology and meditation intervention into an urban middle school. Also, the most recent findings on positive psychology and meditation interventions conducted in school environments will be presented as well.

Keywords: adolescents, contemplative intervention, gratitude, secular meditation, positive psychology, school engagement, Sri Chinmoy

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Authors: Rozelle Labuschagne, Ronel Roos

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Individuals often experience a reduction in physical function, quality of life and basic activities of daily living after surgery. This is exponentially true for high-risk patients, especially the elderly and frail individuals. Not much is known about the physical function, physical activity preferences and factors associated with the six-minute walk test of elderly individuals who would undergo elective abdominal surgery in South Africa. Such information is important to design effective prehabilitation physiotherapy programs prior to elective surgery. The purpose of the study was to describe the demographic profile and physical function of elderly patients who would undergo elective surgery and to determine factors associated with their six-minute walk test distance findings. A cross-sectional descriptive study in elderly patients older than 60 years of age who would undergo elective abdominal surgery were consecutively sampled at a private hospital in Pretoria, South Africa. Participants’ demographics were collected and physical function assessed with the Functional Comorbidity Index (FCI), DeMorton Mobility Index (DEMMI), Lawton-Brody Instrumental Activities of Daily Living Scale (IADL) and six-minute walk test (6MWT). Descriptive and inferential statistics were used for data analysis with IBM SPSS 25. A p-value ≤ 0.05 were deemed statistically significant. The pilot study consisted of 12 participants (female (n=11, 91.7%), male (n=1, 8.3%) with a mean age of 65.8 (±4.5) years, body mass index of 28 (±4.2) kg.m2 with one (8.3%) participant being a current smoker and four (33.3%) participants having a smoking history. Nine (75%) participants lived independently at home and three (25%) had caregivers. Participants reported walking (n=6, 50%), stretching exercises (n=1, 8.3%), household chores & gardening (n=2, 16.7%), biking/swimming/running (n=1, 8.3%) as physical activity preferences. Physical function findings of the sample were: mean FCI score 3 (±1.1), DEMMI score 81.1 (±14.9), IADL 95 (±17.3), 6MWT 435.50 (IQR 364.75-458.50) with percentage 6MWT distance achieved 81.8% (IQR 64.4%-87.5%). A strong negative correlation was observed between 6MWT distance walked and FCI (r = -0.729, p=0.007). The majority of study participants reported incorporating some form of physical activity into their daily life as form of exercise. Most participants did not achieve their predicted 6MWT distance indicating less than optimal levels of physical function capacity. The number of comorbidities as determined by the FCI was associated with the distance that participants could walk with the 6MWT. The results of this pilot study could be used to indicate which elderly individuals would benefit most from a pre-surgical rehabilitation program. The main goal of such a program would be to improve physical function capacity as measured by the 6MWT. Surgeons could refer patients based on age and number of comorbidities, as determined by the FCI, to potentially improve surgical outcomes.

Keywords: abdominal surgery, elderly, physical function, six-minute walk test

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Authors: Ana Luiza Blanco, Luiza de Pádua Penteado, Daniella Pires Nunes

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Ageism is a widespread and prevalent phenomenon that affects older adults and directly affects healthy aging. Identifying the factors that contribute to ageism is important to discuss interventions that minimizes its social and emotional impact. To identify factors related with ageism in Brazilians older adults. Quantitative study, with a cross-sectional and analytical design. 134 older adults completed an online questionnaire about Sociodemographic and Health Characteristics, Discrimination (Ageism Survey), Depressive Symptoms (The Geriatric Depression Scale), Family Function (Family APGAR) and Loneliness. The Mann Whitney and Kruskal Wallis tests were used for data analysis, with a significance level of 5%. The mean age was 66.93 years (sd=0.50), mostly women (84.20%), married (52.60%) and with more than 12 years of schooling (75.93%). The results showed that older adults with a regular self-perception of health had higher median ageism scores when compared to individuals who rated their health as very good or good (p=0.006). The same occurred for individuals with depressive symptoms when compared to those without signs of depression (p=0.001). Regarding family function, it was observed that people with low family functionality tend to suffer more ageism than those with high functionality (p=0.017). Loneliness was also a factor related with the experience of ageism in this study. Lonely individuals had higher median ageism scores (p=0.002). There was relationship between ageism and self-perception of health, depressive symptoms, loneliness and dysfunctional family. Such findings demonstrate the importance of considering the psychosocial determinants of aging to reduce discrimination and promote healthy aging, focusing on social support and educational interventions.

Keywords: ageism, age stereotypes, healthy aging, social conditions

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Authors: Pedro Llanos, Diego García

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This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO₂), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O₂ pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO₂ greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO₂ < 85% for more than 5 seconds) and half of the individuals showed SpO₂ below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O₂ mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO₂ curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.

Keywords: slow onset hypoxia, hypobaric chamber training, altitude sickness, symptoms and altitude, pressure cabin

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Authors: Amira A. A. Abdallah, Amir A. Beltagi

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Background: Core stability training has recently attracted attention for improving muscle balance and optimizing performance in healthy and unhealthy individuals. Purpose: This study investigated the effect of beginner’s core stability exercises on trunk flexors’/extensors’ peak torque ratio and trunk flexors’ and extensors’ peak torques. Methods: Thirty five healthy individuals participated in the study. They were randomly assigned to two groups; experimental “group I, n=20” and control “group II, n=15”. Their mean age, weight and height were 20.7±2.4 vs. 20.3±0.61 years, 66.5±12.1 vs. 68.57±12.2 kg and 166.7±7.8 vs. 164.28 ±7.59 cm. for group I vs. group II. Data were collected using the Biodex Isokinetic system. The participants were tested twice; before and after a 6-week period during which group I performed a core stability training program. Results: The 2x2 Mixed Design ANOVA revealed that there were no significant differences (p>0.025) in the trunk flexors’/extensors’ peak torque ratio between the pre-test and post-test conditions for either group. Moreover, there were no significant differences (p>0.025) in the trunk flexion/extension ratios between both groups at either condition. However, the 2x2 Mixed Design MANOVA revealed significant increases (p<0.025) in the trunk flexors’ and extensors’ peak torques in the post-test condition compared with the pre-test in group I with no significant differences (p>0.025) in group II. Moreover, there was a significant increase (p<0.025) in the trunk flexors’ peak torque only in group I compared with group II in the post-test condition with no significant differences in the other conditions. Interpretation/Conclusion: The improvement in muscle performance indicated by the increase in the trunk flexors’ and extensors’ peak torques in the experimental group recommends including core stability training in the exercise programs that aim to improve muscle performance.

Keywords: core stability, isokinetic, trunk muscles, muscle balance

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Authors: Viktorija Voidogaitė

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Catholic education is based on the belief that every human being is created in the image and likeness of God. It is also influenced by the idea that the Kingdom of Heaven belongs to the humble and vulnerable. These principles emphasize the importance of serving the most vulnerable members of the Church community and promoting inclusivity without discrimination. This perspective emphasizes the need to protect the weakest members with compassion. However, realizing such an ideal in practice proves challenging, as the shortcomings and errors prevalent in any society often stem from the actions of Christians within that society. The evolution of these connections is observed throughout the historical development of Catholic education. In some European countries, Catholic education has become elitist, with limited room for inclusivity. This creates a conspicuous gap between the principles of the Evangelical community and elite Catholic schools and gymnasiums. Some schools appear to be most inclined to educate only those students who best align with their profile, leaving those needing assistance on the margins. As we advance into the third decade of the 21st century, there emerges a fundamental consideration: whether individuals who can assist the underprivileged and the infirm are being emphasized. Yet, it remains an open question whether these individuals will also possess the willingness and capability to construct a community or society that is inclusive and accessible to all.

Keywords: inclusion, Catholic education, inclusive education, becoming

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Authors: Vu Hoang Thu Huong

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Background and Purpose: The effects of Extracorporeal Shockwave Therapy (ESWT) in the participants with knee osteoarthritis (KOA) were unclear on physical performance although its effects on pain had been investiagted. This study aims to explore the effects of ESWT on pain relief and physical performance on KOA. Methods: The studies with the randomized controlled design to investigate the effects of ESWT on KOA were systematically searched using inclusion and exclusion criteria through seven electronic databases including Pubmed etc. between 1990 and Dec 2022. To summarize those data, visual analog scale (VAS) or pain scores were determined for measure of pain intensity. Range of knee motion, or the scores of physical activities including Lequesne index (LI), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were determined for measure of physical performances. The first evaluate after treatment period was define as the effect of post-treatment period or immediately effect; and the last evaluate was defined as the effect of following period or the end effect in our study. Data analysis was performed using RevMan 5.4.1 software. A significant level was set at p<0.05. Results: Eight studies (number of participant= 499) reporting the ESWT effects on mild-to-moderate severity (Grades I to III Kellgren–Lawrence) of KOA were qualified for meta-analysis. Compared with sham or placebo group, the ESWT group had a significant decrease of VAS rest score (0.90[0.12~1.67] as mean difference [95% confidence interval]) and pain score WOMAC (2.49[1.22~3.76]), and a significant improvement of physical performance with a decrease of the scores of WOMAC activities (8.18[3.97~12.39]), LI (3.47[1.68~5.26]), and KOOS (5.87[1.73~ 10.00]) in the post-treatment period. There were also a significant decrease of WOMAC pain score (2.83[2.12~3.53]) and a significant decrease of the scores of WOMAC activities (9.47[7.65~11.28]) and LI (4.12[2.34 to 5.89]) in the following period. Besides, compared with other treatment groups, ESWT also displayed the improvement in pain and physical performance, but it is not significant. Conclusions: The ESWT was effective and valuable method in pain relief as well as in improving physical activities in the participants with mild-to-moderate KOA. Clinical Relevance: There are the effects of ESWT on pain relief and the improvement of physical performance in the with KOA.

Keywords: knee osteoarthritis, extracorporeal shockwave therapy, pain relief, physical performance, shockwave

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Authors: Vanja Skoric

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The paper examines whether the impacts of artificial intelligence (AI) can be meaningfully addressed through the rights-based approach to AI design, investigating in particular how the inclusive, participatory process of assessing the AI impact would make this viable. There is a significant gap between envisioning rights-based AI systems and their practical application. Plausibly, internalizing human rights approach within AI design process might be achieved through identifying and assessing implications of AI features human rights, especially considering the case of vulnerable individuals and communities. However, there is no clarity or consensus on how such an instrument should be operationalised to usefully identify the impact, mitigate harms and meaningfully ensure relevant stakeholders’ participation. In practice, ensuring the meaningful inclusion of those individuals, groups, or entire communities who are affected by the use of the AI system is a prerequisite for a process seeking to assess human rights impacts and risks. Engagement in the entire process of the impact assessment should enable those affected and interested to access information and better understand the technology, product, or service and resulting impacts, but also to learn about their rights and the respective obligations and responsibilities of developers and deployers to protect and/or respect these rights. This paper will provide an overview of the study and practice of the participatory design process for AI, including inclusive impact assessment, its main elements, propose a framework, and discuss the lessons learned from the existing theory. In addition, it will explore pathways for enhancing and promoting individual and group rights through such engagement by discussing when, how, and whom to include, at which stage of the process, and what are the pre-requisites for meaningful and engaging. The overall aim is to ensure using the technology that works for the benefit of society, individuals, and particular (historically marginalised) groups.

Keywords: rights-based design, AI impact assessment, inclusion, harm mitigation

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Authors: Quaid Farooq, Zainab Mujtaba

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The main aim of this paper was to conduct a research regarding social media usage, psychological absenteeism and job performance at workplace in Pakistan. This research examined the effects of social media usage and psychological absenteeism at workplace on job performance of employees. It was a popular belief that social media usage and psychological absenteeism at workplace have a negative relation with job performance. However, to date there was no study to support this argument, and this compelled us to choose this topic and find out the results. Secondly, this research also found effect of social media usage on psychological absenteeism. Despite the theoretical appeal of these variables and significance in today’s workplace environment, no previous study has investigated the relationship between them in detail. Data was collected from a sample (N = 100 paired responses) of employees and supervisors from different organizations in Pakistan. Study results indicate that performance is negatively related to psychological absenteeism, and such individuals were rated as exhibiting low performance level by their supervisors. However, it had no significant relationship with social media. Moreover, psychological absenteeism was positively related to social media. Individuals, who used more social media at workplace, were more psychologically absent at work according to our results.

Keywords: employee, job performance, psychological absenteeism, social media

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Authors: Timothy Scheinert, Eliza Wright

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Background: Link Health is a Boston-based non-profit leveraging in-person and digital platforms to promote health equity. Its primary aim is to financially support low-income individuals through enrollment in federal benefit programs. This study examines the monetary impact of enrollment in several benefit programs. Methodologies: Approximately 17,000 individuals have been screened for eligibility via digital outreach, community events, and in-person clinics. Enrollment and financial distributions are evaluated across programs, including the Affordable Connectivity Program (ACP), Lifeline, LIHEAP, Transitional Aid to Families with Dependent Children (TAFDC), and the Supplemental Nutrition Assistance Program (SNAP). Major Findings: A total of 1,895 individuals have successfully applied, collectively distributing an estimated $1,288,152.00 in aid. The largest contributors to this sum include: ACP: 1,149 enrollments, $413,640 distributed annually. Child Care Financial Assistance (CCFA): 15 enrollments, $240,000 distributed annually. Lifeline: 602 enrollments, $66,822 distributed annually. LIHEAP: 25 enrollments, $48,750 distributed annually. SNAP: 41 enrollments, $123,000 distributed annually. TAFDC: 21 enrollments, $341,760 distributed annually. Conclusions: These results highlight the role of targeted outreach and effective enrollment processes in promoting access to federal benefit programs. High enrollment rates in ACP and Lifeline demonstrate a considerable need for affordable broadband and internet services. Programs like CCFA and TAFDC, despite lower enrollment numbers, provide sizable support per individual. This analysis advocates for continued funding of federal benefit programs. Future efforts can be made to develop screening tools that identify eligibility for multiple programs and reduce the complexity of enrollment.

Keywords: benefits, childcare, connectivity, equity, nutrition

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Authors: Noor Ismael, Somaya Malkawi, Sherin Al Awady, Taleb Ismael

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Background/Significance: Cancer is a serious health condition that affects individuals’ quality of life during and after the course of this condition. Children who have survived cancer and their caregivers may deal with residual physical, cognitive or social disabilities. There is little research on caregivers’ health and wellbeing after cancer. To the authors’ best knowledge; there is no specific research about how caregivers cope with everyday stressors after cancer. Therefore, this study aimed to explore the coping strategies that caregivers of children who have survived cancer utilize to overcome everyday stressors. Methods: This study utilized a descriptive survey design. The sample consisted of 103 caregivers, who visited the health and wellness clinic at a national cancer center (additional demographics are presented in the results). The sample included caregivers of children who were off cancer treatments for at least two years from the beginning of data collection. The institution’s internal review board approved this study. Caregivers who agreed to participate completed the survey. The survey collected caregiver reported demographic information and the Brief COPE which measures caregivers' frequency of engaging in certain coping strategies. The Brief COPE consisted of 14 coping sub-scales, which are self-distraction, active coping, denial, substance use, use of emotional support, use of instrumental support, behavioral disengagement, venting, positive reframing, planning, humor, acceptance, religion, and self-blame. Data analyses included calculating sub-scales’ scores for the fourteen coping strategies and analysis of frequencies of demographics and coping strategies. Results: The 103 caregivers who participated in this study were 62% mothers, 80% married, 45% finished high school, 50% do not work outside the house, and 60% have low family income. Result showed that religious coping (66%) and acceptance (60%) were the most utilized coping strategies, followed by positive reframing (45%), active coping (44%) and planning (43%). The least utilized coping strategies in our sample were humor (5%), behavioral disengagement (8%), and substance-use (10%). Conclusions: Caregivers of children who have survived cancer mostly utilize religious coping and acceptance in dealing with everyday stressors. Because these coping strategies do not directly solve stressors like active coping and planning coping strategies, it is important to support caregivers in choosing and implementing effective coping strategies. Knowing from our results that some caregivers may utilize substance use as a coping strategy, which has negative health effects on caregivers and their children, there must be direct interventions that target these caregivers and their families.

Keywords: caregivers, cancer, stress, coping

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

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Authors: Laetitia Fourie

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Dangerous myths and stereotypes contribute to the fact that persons living with albinism are amongst the most vulnerable groups in society. The prevalence of albinism varies around the world and the World Health Organization estimates that around 1 in 5000 people in Sub-Saharan Africa are affected by this genetic disorder. Persons who are living with the condition usually experience a lack of melanin in their skin, eyes and hair that results in possible physical impairments such as poor eyesight and skin cancers. Being affected by such disorders and consequently classified as an albino, give way for unequal treatment which ultimately requires safeguarding these persons against unfair discrimination - not only on the basis of their race and color (or lack thereof), but also on the basis of their disability. The Constitution of the Republic of South Africa provides that everyone is equal before the law and prohibits unfair discrimination on the grounds of race, color and disability. This right is given effect to by the Employment Equity Act, which strives to eliminate unfair discrimination on similar grounds within any employment policy or practice. An essential non-discrimination measure that can be implemented in the labor market to achieve equality is the duty of reasonable accommodation that rests upon employers. However, reasonable accommodation is only introduced as an affirmative action measure in order to provide equal employment opportunities to the identified designated groups who include black people (defined to include Indians, Chinese and Colored), women and people with disabilities. Even though this duty exists, South African law does not elaborate on the scope of the duty, except for a Disability Code, which does not hold the force of law. Furthermore, in respect of applying affirmative action measures to people with disabilities, the law does not elaborate on the meaning of disability. Considering that persons living with albinism will find it difficult to show that they are black or disabled in order to be acknowledged as part of the designated groups, their access to reasonable accommodation will be limited to a great extent. This paper will aim to illustrate to which extent South African law currently fails to implement its international obligations as a State Party to the Conventions of the United Nations, and how these failures should be corrected in order to serve the needs of all South Africans, including albinos.

Keywords: albinism, disability, equality, South Africa, United Nations

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Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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Authors: Ibrahim Alreshidi, Aseel Albrekeit, Ruaa Alharthi

Abstract:

Background: As a result of the spread of COVID-19 at the beginning of 2020, many governments, including Saudi Arabia, have suspended operations in many agencies. Most dermatologists have restricted their practice, including cosmetic procedures, to ensure social distancing. On the 7th of May 2020, Saudi authorities reduced the restriction of COVID-19 virus preventative measures, allowing clinics to start accepting patients following the ministry of health protocols. Objectives: Evaluation of the public's perception and willingness to undergo cosmetic procedures during COVID-19 outbreaks in Saudi Arabia. Materials and methods: A descriptive, cross-sectional, questionnaire-based study was carried out among the individuals who lack typical symptoms of COVID-19 infection in Saudi Arabia. A self-designed web-based questionnaire was developed; content face validity and a pilot study were done. The questionnaire was distributed electronically from the 8th of May until the 31st of May 2020. Results: A total of 656 individuals who lack typical symptoms of COVID-19 infection were included in this analysis. Only 10.5% of participants expressed their will to do cosmetic procedures during the COVID-19 pandemic. More than 90% of the participants believed that the COVID-19 pandemic was either somewhat serious (52.9%) or very serious (38.7%). The willingness to do cosmetic procedures during the COVID-19 pandemic remained unaltered when the price was discounted (p<0.001) and when infection control measures were ensured (p<0.001). Conclusion: The COVID-19 pandemic had a negative impact on the practice of cosmetic dermatology. Fear of transferring the infection to a beloved home member is the main reason to avoid these procedures. Generating well-structured safety guidelines to decrease the risk of this unusual virus transmission in dermatology practice and creating financial incentives may help increase the public willingness to do these cosmetic procedures during this pandemic.

Keywords: COVID-19 pandemic, cosmetic procedures, questionnaire, dermatology

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Authors: Abdreheman Seid Abdella

Abstract:

This study examined instructors willingness, self-efficacy beliefs, attitudes and knowledge about provisions of instructional accommodations for students with disabilities in universities. Major concepts used in this study operationally defined and some models of disability were reviewed. Questionnaires were distributed to a total of 181 instructors from four universities and quantitative data was generated. Then to analyze the data, appropriate methods of data analysis were employed. The result indicated that on average instructors had positive willingness, strong self-efficacy beliefs and positive attitudes towards providing instructional accommodations. In addition, the result showed that the majority of participants had moderate level of knowledge about provision of instructional accommodations. Concerning the relationship between instructors background variables and dependent variables, the result revealed that location of university and awareness raising training about Inclusive Education showed statistically significant relationship with all dependent variables (willingness, self-efficacy beliefs, attitudes and knowledge). On the other hand, gender and college/faculty did not show a statistically significant relationship. In addition, it was found that among the inter-correlation of dependent variables, the correlation between attitudes and willingness to provide accommodations was the strongest. Furthermore, using multiple linear regression analysis, this study also indicated that predictor variables like self-efficacy beliefs, attitudes, knowledge and teaching methodology training made statistically significant contribution to predicting the criterion willingness. Predictor variables like willingness and attitudes made statistically significant contribution to predicting self-efficacy beliefs. Predictor variables like willingness, Special Needs Education course and self-efficacy beliefs made statistically significant contribution to predict attitudes. Predictor variables like Special Needs Education courses, the location of university and willingness made statistically significant contribution to predicting knowledge. Finally, using exploratory factor analysis, this study showed that there were four components or factors each that represent the underlying constructs of willingness and self-efficacy beliefs to provide instructional accommodations items, five components for attitudes towards providing accommodations items and three components represent the underlying constructs for knowledge about provisions of instructional accommodations items. Based on the findings, recommendations were made for improving the situation of instructional accommodations in Ethiopian universities.

Keywords: willingness, self-efficacy belief, attitude, knowledge

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Authors: Francis Nanda Prakash Monteiro, Shyna Quadras, Tanush Shetty

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The association between human physique and morbidity and mortality resulting from coronary artery disease has been studied extensively over several decades. Multiple studies have also been done on the correlation between grade of atherosclerosis, coronary artery diseases and anthropometrical measurements. However, the number of autopsy-based studies drastically reduces this number. It has been suggested that while in living subjects, it would be expensive, difficult, and even harmful to subject them to imaging modalities like CT scans and procedures involving contrast media to study mild atherosclerosis, no such harm is encountered in study of autopsy cases. This autopsy-based study was aimed to correlate the anthropometric measurements and indices of obesity, such as waist circumference (WC), hip circumference (HC), body mass index (BMI) and waist hip ratio (WHR) with the degree of atherosclerosis in the right coronary artery (RCA), main branch of the left coronary artery (LCA) and the left anterior descending artery (LADA) in 95 South Indian origin victims of both the genders between the age of 18 years and 75 years. The grading of atherosclerosis was done according to criteria suggested by the American Heart Association. The study also analysed the correlation of the anthropometric measurements and indices of obesity with the number of coronaries affected with atherosclerosis in an individual. All the anthropometric measurements and the derived indices were found to be significantly correlated to each other in both the genders except for the age, which is found to have a significant correlation only with the WHR. In both the genders severe degree of atherosclerosis was commonly observed in LADA, followed by LCA and RCA. Grade of atherosclerosis in RCA is significantly related to the WHR in males. Grade of atherosclerosis in LCA and LADA is significantly related to the WHR in females. Significant relation was observed between grade of atherosclerosis in RCA and WC, and WHR, and between grade of atherosclerosis in LADA and HC in males. Significant relation was observed between grade of atherosclerosis in RCA and WC, and WHR, and between grade of atherosclerosis in LADA and HC in females. Anthropometric measurements/indices of obesity can be an effective means to identify high risk cases of atherosclerosis at an early stage that can be effective in reducing the associated cardiac morbidity and mortality. A person with anthropometric measurements suggestive of mild atherosclerosis can be advised to modify his lifestyle, along with decreasing his exposure to the other risk factors. Those with measurements suggestive of higher degree of atherosclerosis can be subjected to confirmatory procedures to start effective treatment.

Keywords: atherosclerosis, coronary artery disease, indices, obesity

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Authors: Wei-Kuang Liu, Ya-Hsu Chiang

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In the coming of an aging society, the issues of living quality, health care, and social security for the elderly have been gradually taken seriously. In order to maintain favorable living condition, urban societies are also facing the challenge of disasters caused by extreme climate change. However, in the practice of disaster prevention, elderly people are always weak due to their physiological conditions. That is to say, in the planning of resilient urbanism, the aging society is relatively in need of more care. Thus, this research aims to map areas where have high-density elderly population and fragile environmental condition in Taiwan, and to understand the actual situation of disaster prevention management in these areas, so as to provide suggestions for the development of intellectual resilient urban management. The research takes the cities of Taoyuan and Taichung as examples for explorations. According to GIS mapping of areas with high aging index, high-density population and high flooding potential, the communities of Sihai and Fuyuan in Taoyuan and the communities of Taichang and Nanshih in Taichung are highlighted. In these communities, it can be found that there are more elderly population and less labor population with high-density living condition. In addition, they are located in the areas where they have experienced severe flooding in the recent past. Based on a series of interviews with community organizations, there is only one community out of the four using flood information mobile app and Line messages for the management of disaster prevention, and the others still rely on the traditional approaches that manage the works of disaster prevention by their community security patrol teams and community volunteers. The interview outcome shows that most elderly people are not interested in learning the use of intellectual devices. Therefore, this research suggests to keep doing the GIS mapping of areas with high aging index, high-density population and high flooding potential for grasping the high-risk communities and to help develop smart monitor and forecast systems for disaster prevention practice in these areas. Based on case-study explorations, the research also advises that it is important to develop easy-to-use bottom-up and two-way immediate communication mechanism for the management of aging society’s disaster prevention.

Keywords: aging society, disaster prevention, GIS, resilient, Taiwan

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Authors: V. U. Onyemauwa

Abstract:

Conflicts have always been part of human societies. So long as there is interaction amongst individuals or societies, there are bound to be conflicts as a result of the fact that interests among individuals and societies vary. The issue of conflict has become one of the regular headlines in the daily news of the Nigerian and global media today. Nigerian polity has suffered from one conflict or another, ranging from religious, civil, political, cultural, regional and ethnic violence. It has been found out that, the most disturbing part of these acts of conflicts in Nigeria and around the globe is that most of them have traced their roots to religion. Even some perpetrators of these acts of conflicts most of the time justify their actions with religion, thereby wrongly making religion an object of conflict and violence. In this regard, the study seeks to project religion as a potent tool for conflict resolution because it has a way of permeating through the hearts of men. It has a special responsibility of identifying conflicts and proffer solutions. It also has to provide theological reasoning as to why and how these conflicts come about and how they can possibly be solved. Religious actors are known to contribute to the processes of structural reform necessary for the restoration of productive social relations and political stability after a period of conflict and human rights abuses. The study examines the modalities for projecting religious conflict management strategies in Nigeria using an analysis of relevant documents as well as Black’s Social Control Theory and Thomas-Kilmann’s Model of Conflict Management as its theoretical frameworks. It recommends for a religiously-based means of conflict resolution in Nigeria. Religious individuals and faith-based organisations, as carriers of religious ideas are implore to play active roles in conflict resolution and peace-building in Nigeria by creating conducive environment for peaceful talks, mediation and reconciliation. This will enhance social cohesion, provides solid foundation for peace, progress and development in the society.

Keywords: conflict, peace, religion, resolution

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Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

Abstract:

Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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Authors: James Moran, Anusarn Permsuwan

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This paper compares oscillations in the dry friction coefficient in different journal bearings. Measurements are made of the average and standard deviation in the coefficient of friction as a function of sliding velocity. The standard deviation of the friction coefficient changed dramatically with sliding velocity. The magnitude and frequency of the oscillations were a function of the velocity. A numerical model was developed for the frictional oscillations. There was good agreement between the model and results. Five different materials were used as the sliding surfaces in the experiments, Aluminum, Bronze, Mild Steel, Stainless Steel, and Nylon.

Keywords: Coulomb friction, dynamic friction, non-lubricated bearings, frictional oscillations

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Authors: Krisztina Bohacs, Klaudia Markus

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To author’s best knowledge we are in absence of studies on cognitive program evaluation and we are certainly short of programs that prove to have high effect sizes with strong retention results. The purpose of our study was to investigate the effectiveness of a comprehensive cognitive training program, namely BrainRx. This cognitive rehabilitation program target and remediate seven core cognitive skills and related systems of sub-skills through repeated engagement in game-like mental procedures delivered one-on-one by a clinician, supplemented by digital training. A larger sample of children with learning disability were given pretest and post-test cognitive assessments. The experimental group completed a twenty-week cognitive training program in a BrainRx center. A matched control group received another twenty-week intervention with Feuerstein’s Instrumental Enrichment programs. A second matched control group did not receive training. As for pre- and post-test, we used a general intelligence test to assess IQ and a computer-based test battery for assessing cognition across the lifespan. Multiple regression analyses indicated that the experimental BrainRx treatment group had statistically significant higher outcomes in attention, working memory, processing speed, logic and reasoning, auditory processing, visual processing and long-term memory compared to the non-treatment control group with very large effect sizes. With the exception of logic and reasoning, the BrainRx treatment group realized significantly greater gains in six of the above given seven cognitive measures compared to the Feuerstein control group. Our one-year retention measures showed that all the cognitive training gains were above ninety percent with the greatest retention skills in visual processing, auditory processing, logic, and reasoning. The BrainRx program may be an effective tool to establish long-term cognitive changes in case of students with learning disabilities. Recommendations are made for treatment centers and special education institutions on the cognitive training of students with special needs. The importance of our study is that targeted, systematic, progressively loaded and intensive brain training approach may significantly change learning disabilities.

Keywords: cognitive rehabilitation training, cognitive skills, learning disability, permanent structural cognitive changes

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Authors: Pranee Suecharoen, Ratchadaporn Soontornpas, Jaturat Kanpittaya

Abstract:

Background: Contrast media has an important role for disease diagnosis through detection of pathologies. Contrast media can, however, cause adverse reactions after administration of its agents. Although non-ionic contrast media are commonly used, the incidence of adverse events is relatively low. The most common reactions found (10.5%) were mild and manageable and/or preventable. Pharmacists can play an important role in evaluating adverse reactions, including awareness of the specific preparation and the type of adverse reaction. As most common types of adverse reactions are idiosyncratic or pseudo-allergic reactions, common standards need to be established to prevent and control adverse reactions promptly and effectively. Objective: To measure the effect of using tools for symptom evaluation in order to reduce the severity, or prevent the occurrence, of adverse reactions from contrast media. Methods: Retrospective review descriptive research with data collected on adverse reactions assessment and Naranjo’s algorithm between June 2015 and May 2016. Results: 158 patients (10.53%) had adverse reactions. Of the 1,500 participants with an adverse event evaluation, 137 (9.13%) had a mild adverse reaction, including hives, nausea, vomiting, dizziness, and headache. These types of symptoms can be treated (i.e., with antihistamines, anti-emetics) and the patient recovers completely within one day. The group with moderate adverse reactions, numbering 18 cases (1.2%), had hypertension or hypotension, and shortness of breath. Severe adverse reactions numbered 3 cases (0.2%) and included swelling of the larynx, cardiac arrest, and loss of consciousness, requiring immediate treatment. No other complications under close medical supervision were recorded (i.e., corticosteroids use, epinephrine, dopamine, atropine, or life-saving devices). Using the guideline, therapies are divided into general and specific and are performed according to the severity, risk factors and ingestion of contrast media agents. Patients who have high-risk factors were screened and treated (i.e., prophylactic premedication) for prevention of severe adverse reactions, especially those with renal failure. Thus, awareness for the need for prescreening of different risk factors is necessary for early recognition and prompt treatment. Conclusion: Studying adverse reactions can be used to develop a model for reducing the level of severity and setting a guideline for a standardized, multidisciplinary approach to adverse reactions.

Keywords: role of pharmacist, management of adverse reactions, guideline for contrast media, non-ionic contrast media

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Authors: Noureddine Seddari, Mohamed Belaoued, Salah Bougueroua

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The modeling of complex systems is generally based on the decomposition of their components into sub-systems easier to handle. This division has to be made in a methodical way. In this paper, we introduce an industrial control system modeling and simulation based on the Multi-Agent System (MAS) methodology AALAADIN and more particularly the underlying conceptual model Agent/Group/Role (AGR). Indeed, in this division using AGR model, the overall system is decomposed into sub-systems in order to improve the understanding of regulation and control systems, and to simplify the implementation of the obtained agents and their groups, which are implemented using the Multi-Agents Development KIT (MAD-KIT) platform. This approach appears to us to be the most appropriate for modeling of this type of systems because, due to the use of MAS, it is possible to model real systems in which very complex behaviors emerge from relatively simple and local interactions between many different individuals, therefore a MAS is well adapted to describe a system from the standpoint of the activity of its components, that is to say when the behavior of the individuals is complex (difficult to describe with equations). The main aim of this approach is the take advantage of the performance, the scalability and the robustness that are intuitively provided by MAS.

Keywords: complex systems, modeling and simulation, industrial control system, MAS, AALAADIN, AGR, MAD-KIT

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Authors: Bryan Young, Andrew Wodehouse, Marion Sheridan

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The availability of working memory has long been identified as a critical aspect of an instructional design. Many conventional instructional procedures impose irrelevant or unrelated cognitive loads on the learner due to the fact that they were created without contemplation, or understanding, of cognitive work load. Learning to physically operate traditional products can be viewed as a learning process akin to any other. As such, many of today's products, such as cars, boats, and planes, which have traditional controls that predate modern user-centered design techniques may be imposing irrelevant or unrelated cognitive loads on their operators. The goal of the research was to investigate the fundamental relationships between physical inputs, resulting actions, and learnability. The results showed that individuals can quickly adapt to input/output reversals across dimensions, however, individuals struggle to cope with the input/output when the dimensions are rotated due to the resulting increase in cognitive load.

Keywords: cognitive load theory, instructional design, physical product interactions, usability design

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Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

Abstract:

Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

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