Search results for: Susan Harrison

Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: Kelsey Fortin, Susan Harvey

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The intersection between hunger and health outcomes is beginning to gain traction among the research community. With new interventions focusing on collaborations between the medical and social service sectors, this study aimed to understand the acceptability and approach of a health coaching intervention within a county-wide Midwest food pantry. Through formative research, the study used mixed methods to review secondary data and conduct surveys and semi-structured interviews with food pantry clients (n=30), staff (n=7), and volunteers (n=10). Supplemental secondary data collected and provided by pantry staff were reviewed to understand the broader pantry context of clientele health and health behaviors, annual food donations, and current pantry programming. Results from secondary data showed that the broader pantry client population reported high rates of chronic disease, low consumption of fruits and vegetables, and poor self-reported health, while annual donation data showed increases in produce availability on pantry shelves. This disconnect between produce availability, client health status, and behaviors was supported in the current study, with pantry staff and volunteers reporting lack of knowledge in produce selection and preparation being amongst the most common client inquiries and barriers to healthy food selection. Additional supports to secondary data came from pantry clients in the current study through self-reported high rates of both individual (60%, n=18) and household (43%, n=13 ) disease diagnosis, low consumption of fruits and vegetables averaging zero to one servings of vegetables (67%, n=20) and fruits (47%, n=14) per day, and low levels of physical activity averaging zero to 120 minutes per week (67%, n=20). Further, pantry clients provided health coaching programmatic recommendations through interviews with feedback such as non-judgmental coaching, accountability measures, and providing participant incentives as considerations for future program design and approach. Volunteers and staff reported the need for client education in food preparation, basic nutrition and physical activity, and the need for additional health expertise to educate and respond to diet related nutrition recommendations. All three stakeholder groups supported hosting a health coach within the pantry to focused on nutrition, physical activity, and health programming, with one client stating, 'I am hoping it really works out [the health coaching program]. I think it would be great for something like this to be offered for someone that isn’t knowledgeable like me.' In conclusion, high rates of chronic disease, partnered with low food, nutrition, and physical activity literacy among pantry clients, demonstrates the need to address health behaviors. With all three stakeholder groups showing acceptability of a health coaching program, partnered with existing literature showing health coaching success as a behavior change intervention, further research should be conducted to pilot the design and implementation of such a program in the pantry setting.

Keywords: food insecurity, formative research, food pantries, health coaching, hunger and health

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Authors: Susan Grantham, Emily S. Kinsky

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As the popularity of K-drama viewership increases, the depiction of journalists’ news gathering and distribution behavior in these series can have an impact on viewers’ perceptions of journalism practices in Korea. Studies have shown that viewers are impacted both by their impressions of actual journalists delivering news, as well as by fictional portrayals of journalists they have seen. As mistrust in the media grows internationally, it is important to understand how journalists are viewed. K-dramas are an increasingly popular export and consumed across the globe. In 2021 Netflix had 74 million subscribers in the US/Canadian market, about 36% of its overall subscriber base, with an in- crease of about 16 million new subscribers during the pandemic. A Statista November 2023 survey found that K-dramas are moderately (27%) or very popular (41%). While Hallyu has grown increasingly in the past decade, between 2019 and 2021, viewership numbers for TV series produced in South Korea went up a staggering 200% in the U.S. Additionally, a 2023 KOCCA report about K-drama viewership in the U.S. found that, within the past year, male viewership became nearly equal to female viewership. This study evaluated how viewers perceive journalists and journalistic practices in South Korea as portrayed in eight K-drama series. Six in-depth interviews and two focus groups were conducted to evaluate viewer perceptions of journalism practices as portrayed in K-dramas. This study builds upon two previous research projects: a content analysis of the same eight K-dramas featuring journalists in a primary role and whose journalistic work is pivotal to the plot, followed by subsequent in-depth interviews with South Korean journalists. The K-dramas in the sample featured both print and broadcast journalists. Using clips from these K-drama series that featured journalistic practices, as well as pressure faced by journalists, participants were be asked a series of questions about their impressions of journalists and journalism in South Korea and how realistic they perceived these portrayals to be. The participants were comprised of viewers who frequently watched K-dramas and occasionally/seldom watched K-dramas. The initial findings show that regardless of how frequently the participants watched K-dramas, they indicated that the presentation of the journalists seemed pretty realistic, and that the journalists behaved ethically. Participants felt their portrayal was relatable to their impression of how journalists behaved in the United States. This was also true in terms of the internal pressure shown in the clips toward journalists that featured behavior by the journalists’ supervisors focused on supporting the media company’s political and business positions. The amount of negative feedback toward the journalists from the general public, as shown in the clips, seemed less realistic to the participants. The idea of ‘fake news’ as a function of the news consumer’s own personal beliefs, versus actual misinformation, resonated with the participants. Additional research is being conducted. Because Korea is an important source of news and information in East Asia, it is important to understand the potential perceptions of consumers and how they view journalistic practices in Korea.

Keywords: ethical journalism, K-drama, Korean journalists, viewer perceptions

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Authors: Susan C. Graham

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Authenticity has grown to be ubiquitous within the tourism vernacular. Yet, agreement regarding what authenticity means in relation to tourism remains nebulous. In its simplest form, authenticity in tourism refers to products and experiences that provide insights into the social, cultural, economic, natural, historical, and political life of a place. But this definition is unwieldy in its scope and may not help industry leaders nor tourist in identifying that which is authentic. Much of what is projected as authentic is a carefully curated and crafted message developed by marketers to appeal to visitors and bears little resemblance to the everyday lives of locals. So perhaps one way to identify authentic tourism experiences is to ask locals themselves. The purpose of this study was to explore the perspectives of locals with respect to what constituted an authentic tourism experience in Prince Edward Island (PEI), Canada. Over 600 volunteers in a tourism research panel were sent a survey asking them to describe authentic PEI experiences within ten sub-categories relevant to the local tourism industry. To make participation more manageable, each respondent was asked their perspectives on any three of the tourism sub-categories. Over 400 individuals responded, providing 1391 unique responses. The responses were grouped thematically using interpretive phenomenological analysis whereby the participants’ responses were clustered into higher order groups to extract meaning. Two interesting thematic observations emerged: first, that respondents tended to clearly articulate and differentiate between intra- versus interpersonal experiences as a means of authentically experiencing PEI; and second, while respondents explicitly valued unstaged experiences over staged, several exceptions to this general rule were expressed. Responses could clearly be grouped into those that emphasized “going off the beaten path,” “exploring pristine and untouched corners,” “lesser known,” “hidden”, “going solo,” and taking the opportunity to “slow down.” Each of these responses was “self” centered, and focused on the visitor discovering and exploring in search of greater self-awareness and inner peace. In contrast, other responses encouraged the interaction of visitors with locals as a means of experiencing the authentic place. Respondents sited “going deep-sea fishing” to learn about local fishers and their communities, stopping by “local farm stands” and speaking with farmers who worked the land for generations,” patronizing “local restaurants, pubs, and b&bs”, and partaking in performances or exhibits by local artists. These kinds of experiences, the respondents claimed, provide an authentic glimpse into a place’s character. The second set of observations focused on the distinction between staged and unstaged experiences, with respondents overwhelmingly advocating for unstaged. Responses were clear in shunning “touristy,” “packaged,” and “fake” offerings for being inauthentic and misrepresenting the place as locals view it. Yet many respondents made exceptions for certain “staged” experiences, including (quite literally) the stage production of Anne of Green Gables based on the novel of the same name, the theatrical re-enactment of the founding of Canada, and visits to PEI’s many provincial and national parks, all of which respondents considered both staged and authentic at the same time.

Keywords: authentic, local, Prince Edward Island, tourism

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Authors: Lindsey D. Sams, Dean R. Gorman, Cathy D. Lirgg, Steve W. Dittmore, Jack C. Kern

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Golf is a lifetime sport that provides numerous physical and psychological benefits. The game has struggled with attrition and retention within minority groups and this has exposed the lack of a modified introduction to the game that is uniformly accessible and developmentally appropriate. Factors that have been related to sport participatory behaviors include perceived competence, enjoyment and intention. The purpose of this study was to examine self-reported perception differences in competence and enjoyment between learners using modified and traditional equipment as well as the potential effects these factors could have on intent for future participation. For this study, SNAG Golf was chosen to serve as the scaled equipment used by the modified equipment group. The participants in this study were 99 children (24 traditional equipment users/ 75 modified equipment users) located across the U.S. with ages ranging from 7 to 12 years (2nd-5th grade). Utilizing a convenience sampling method, data was obtained on a voluntary basis through surveys measuring children’s golf participation and self-perceptions concerning perceived competence, enjoyment and intention to continue participation. The scales used for perceived competence and enjoyment included Susan Harter’s Self-Perception Profile for Children (SPPC) along with the Physical Activity Enjoyment Scale (PACES). Analysis revealed no significant differences for enjoyment, perceived competence or intention between children learning with traditional golf equipment and modified golf equipment. This was true even though traditional equipment users reported significantly higher experience levels than that of modified users. Intention was regressed on the enjoyment and perceived competence variables. Congruent with current literature, enjoyment was a strong predictor of intention to continue participation, for both groups. Modified equipment users demonstrated significantly lower experience levels but reported similar levels of competence, enjoyment and intent to continue participation as reported by the more experienced, and potentially more skilled, traditional users. The ability to immediately generate these positive affects suggests the potential adoption of a more effective way to learn golf and a method that is conducive to participatory behaviors related to attrition and retention. These implications in turn, highlight an equipment candidate ideal for inception into physical education programs where new learners are introduced to various sports in safe and developmentally appropriate environments. A major goal of this study was to provide foundational research that instigates the further examination of golf’s introductory teaching methodologies, as there is a lack of its presence in current literature. Future research recommendations range from improvements in the current research design to expansive approaches related to the topic, such as progressive skill development, knowledge of the game’s tactical and strategic concepts, playing ability and teaching effectiveness when utilizing modified versus traditional equipment.

Keywords: adaptive sports, enjoyment, golf participation, modified equipment, perceived competence, SNAG golf

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Authors: Jean Ware, Susan W. Jones

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Background: The benefits of grammar instruction in the teaching of writing is contested in most English speaking countries. A majority of Anglophone countries abandoned the teaching of grammar in the 1950s based on the conclusions that it had no positive impact on learners’ development of reading, writing, and language. Although the decontextualised teaching of grammar is not helpful in improving writing, a curriculum with a focus on grammar in an embedded and meaningful way can help learners develop their understanding of the mechanisms of language. Although British learners are generally not taught grammar rules explicitly, learners in schools in France, the Netherlands, and Germany are taught explicitly about the structure of their own language. Exposing learners to grammatical analysis can help them develop their understanding of language. Indeed, if learners are taught that each part of speech has an identified role in the sentence. This means that rather than have to memorise lists of words or spelling patterns, they can focus on determining each word or phrase’s task in the sentence. These processes of categorisation and deduction are higher order thinking skills. When considering definitions of dyslexia available in Great Britain, the explicit teaching of grammar in context could help learners with persistent literacy difficulties. Indeed, learners with dyslexia often develop strengths in problem solving; the teaching of grammar could, therefore, help them develop their understanding of language by using analytical and logical thinking. Aims: This study aims at gaining a further understanding of how the explicit teaching of grammar in context can benefit learners with persistent literacy difficulties. The project is designed to identify ways of adapting existing grammar focussed teaching materials so that learners with specific learning difficulties such as dyslexia can use them to further develop their writing skills. It intends to improve educational practice through action, analysis and reflection. Research Design/Methods: The project, therefore, uses an action research design and multiple sources of evidence. The data collection tools used were standardised test data, teacher assessment data, semi-structured interviews, learners’ before and after attempts at a writing task at the beginning and end of the cycle, documentary data and lesson observation carried out by a specialist teacher. Existing teaching materials were adapted for use with five Year 9 learners who had experienced persistent literacy difficulties from primary school onwards. The initial adaptations included reducing the amount of content to be taught in each lesson, and pre teaching some of the metalanguage needed. Findings: Learners’ before and after attempts at the writing task were scored by a colleague who did not know the order of the attempts. All five learners’ scores were higher on the second writing task. Learners reported that they had enjoyed the teaching approach. They also made suggestions to be included in the second cycle, as did the colleague who carried out observations. Conclusions: Although this is a very small exploratory study, these results suggest that adapting grammar focused teaching materials shows promise for helping learners with persistent literacy difficulties develop their writing skills.

Keywords: explicit teaching of grammar in context, literacy acquisition, persistent literacy difficulties, writing skills

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Anne Tetens, Susan Andersen, Lars Ole Bonde, Pia Jeppesen, Katrine Rich Madsen

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Background: The World Health Organization (WHO) has emphasized the critical need for feasible and effective school-based mental health promotion interventions. High-quality music education in school has been suggested to promote well-being, inclusion, and positive relations, which are essential for children’s mental health. This study explores the potential of choir singing as a distinct approach to enhance children’s mental health within the school setting. ‘Everyone Can Sing’ is a class-based mental health promotion intervention for children in grades 0-3 (ages 5-10) in Danish primary school, which integrates choir singing into the students’ normal school schedule twice a week to promote mental health through the increase of school well-being, class coherence and social inclusion. The intervention uses trained choir leaders to lead the lessons in close collaboration with the class teacher, placing a distinct emphasis on well-being and the inclusive aspect of musical expression through body and voice. Aim: The aim of the study is to evaluate the feasibility of the Everyone Can Sing intervention with the specific objective to assess implementation and changes in mental health parameters, including school well-being, class coherence and social inclusion. Methodologies: The study is a feasibility study of a one-year intervention, which started in January 2024 and is being implemented in grades 0-3 (ages 5-10) across three different Danish primary schools. It is designed according to a mixed methods approach, including both quantitative and qualitative methods. Baseline questionnaires were obtained from students, parents and teachers, and follow-up is planned at 12 months. Participant observations of class choir and individual and group interviews with students, teachers, choir leaders, and school management are collected during the intervention period. The study uses the validated ‘Strengths and Difficulties Questionnaire’ for parent- and teacher-reports. The student questionnaire, which assesses school well-being, class coherence, social inclusion and indicators of mental health, was developed and validated for this study. Participant observations and interviews provide in-depth insights into the implementation process and participants’ experiences of the mental health-promoting potential of the intervention. Findings: The study included 41 classes across three schools (N=904) and questionnaire data from students (n=845, = 93%), teachers (n=890, = 98%), and parents (n=608, = 67%) at baseline. Follow-up data will be obtained in January 2025. While collection and analyses of data are still ongoing, preliminary implementation findings based on interviews and observations indicate high levels of engagement and acceptability. At 6 months into the intervention period, the study protocol is on track and suggests that the intervention is well-received. Further findings and analyses will be presented. The final results of the study will be used to decide whether the AKS intervention should proceed to a future, full-size effectiveness trial, return to refinement of the intervention or the evaluation design, or stop. Contributions: This study will provide valuable insights into new approaches to school-based mental health promotion initiatives. If feasible, the vision is to implement the intervention or elements of it in primary schools across all five Danish regions, potentially lowering the mental health burden.

Keywords: child mental health, early childhood, mental health promotion, mixed methods research, school-based intervention.

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Authors: Damiano Omari, Topirian Kerempe, Dibo Sama, Walter Wafula, Sharon Chepkoech, Chrispine Juma, Gilbert Kirui, Simon Mburu, Susan Keino

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The One Health concept was officially adopted by the international organizations and scholarly bodies in 1984. It aims at combining human, animal and environmental components to address global health challenges. Using collaborative efforts optimal health to people, animals, and the environment can be achieved. One health approach plays a significant approach role in prevention and control of zoonosis diseases. It has also been noted that 75% of new emerging human infectious diseases are zoonotic. In Kenya, one health has been embraced and strongly advocated for by One Health East and Central Africa (OHCEA). It was inaugurated on 17th of October 2010 at a historic meeting facilitated by USAID with participants from 7 public health schools, seven faculties of veterinary medicine in Eastern Africa and 2 American universities (Tufts and University of Minnesota) in addition to respond project staff. The study was conducted in Loitoktok Sub County, specifically in the Amboseli Ecosystem. The Amboseli ecosystem covers an area of 5,700 square kilometers and stretches between Mt. Kilimanjaro, Chyulu Hills, Tsavo West National park and the Kenya/Tanzania border. The area is arid to semi-arid and is more suitable for pastoralism with a high potential for conservation of wildlife and tourism enterprises. The ecosystem consists of the Amboseli National Park, which is surrounded by six group ranches which include Kimana, Olgulului, Selengei, Mbirikani, Kuku and Rombo in Loitoktok District. The Manyatta of study was Osiram Cultural Manyatta in Mbirikani group ranch. Apart from visiting the Manyatta, we also visited the sub-county hospital, slaughter slab, forest service, Kimana market, and the Amboseli National Park. The aim of the study was to identify the one health issues facing the community. This was done by a conducting a community needs assessment and prioritization. Different methods were used in data collection for the qualitative and numerical data. They include among others; key informant interviews and focus group discussions. We also guided the community members in drawing their Resource Map this helped identify the major resources in their land and also help them identify some of the issues they were facing. Matrix piling, root cause analysis, and force field analysis tools were used to establish the one health related priority issues facing community members. Skits were also used to present to the community interventions to the major one health issues. Some of the prioritized needs among the community were water scarcity and inadequate markets for their beadwork. The group intervened on the various needs of the Manyatta. For water scarcity, we educated the community on water harvesting methods using gutters as well as proper storage by the use of tanks and earth dams. The community was also encouraged to recycle and conserve water. To improve markets; we educated the community to upload their products online, a page was opened for them and uploading the photos was demonstrated to them. They were also encouraged to be innovative to attract more clients.

Keywords: Amboseli ecosystem, community interventions, community needs assessment and prioritization, one health issues

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Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

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Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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Authors: Philip A. Szlosek, M. Susan Guyer, Mary G. Barnum, Elizabeth M. Mullin

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In the United States, athletic training is a healthcare profession that encompasses the prevention, examination, diagnosis, treatment, and rehabilitation of injuries and medical conditions. Athletic trainers work under the direction of or in collaboration with a physician and are recognized by the American Medical Association as allied healthcare professionals. Internationally, this profession is often known as athletic therapy. As healthcare professionals, athletic trainers must be prepared for autonomous practice immediately after graduation. However, new athletic trainers have been shown to have clinical areas of strength and weakness.To better assess professional readiness and improve the preparedness of new athletic trainers, the factors of athletic training professional readiness must be defined. Limited research exists defining the holistic aspects of professional readiness needed for athletic trainers. Confirming the factors of professional readiness in athletic training could enhance the professional preparation of athletic trainers and result in more highly prepared new professionals. The objective of this study was to further explore and confirm the factors of professional readiness in athletic training. Authors useda qualitative design based in grounded theory. Participants included athletic trainers with greater than 24 months of experience from a variety of work settings from each district of the National Athletic Trainer’s Association. Participants took the demographic questionnaire electronically using Qualtrics Survey Software (Provo UT). After completing the demographic questionnaire, 20 participants were selected to complete one-on-one interviews using GoToMeeting audiovisual web conferencing software. IBM Statistical Package for the Social Sciences (SPSS, v. 21.0) was used to calculate descriptive statistics for participant demographics. The first author transcribed all interviews verbatim and utilized a grounded theory approach during qualitative data analysis. Data were analyzed using a constant comparative analysis and open and axial coding. Trustworthiness was established using reflexivity, member checks, and peer reviews. Analysis revealed four overarching themes, including management, interpersonal relations, clinical decision-making, and confidence. Management was categorized as athletic training services not involving direct patient care and was divided into three subthemes, including administration skills, advocacy, and time management. Interpersonal Relations was categorized as the need and ability of the athletic trainer to properly interact with others. Interpersonal relations was divided into three subthemes, including personality traits, communication, and collaborative practice. Clinical decision-making was categorized as the skills and attributes required by the athletic trainer whenmaking clinical decisions related to patient care. Clinical decision-making was divided into three subthemes including clinical skills, continuing education, and reflective practice. The final theme was confidence. Participants discussed the importance of confidence regarding relationships building, clinical and administrative duties, and clinical decision-making. Overall, participants explained the value of a well-rounded athletic trainer and emphasized that athletic trainers need communication and organizational skills, the ability to collaborate, and must value self-reflection and continuing education in addition to having clinical expertise. Future research should finalize a comprehensive model of professional readiness for athletic training, develop a holistic assessment instrument for athletic training professional readiness, and explore the preparedness of new athletic trainers.

Keywords: autonomous practice, newly certified athletic trainer, preparedness for professional practice, transition to practice skills

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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

Abstract:

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 201

Authors: Sam Weber, Deepak Mishra, Susan Wilde, Elizabeth Kramer

Abstract:

The frequency and severity of cyanobacteria harmful blooms (CyanoHABs) have been increasing over time, with point and non-point source eutrophication and shifting climate paradigms being blamed as the primary culprits. Excessive nutrients, warm temperatures, quiescent water, and heavy and less regular rainfall create more conducive environments for CyanoHABs. CyanoHABs have the potential to produce a spectrum of toxins that cause gastrointestinal stress, organ failure, and even death in humans and animals. To promote enhanced, proactive CyanoHAB management, risk modeling using geospatial tools can act as predictive mechanisms to supplement current CyanoHAB monitoring, management and mitigation efforts. The risk maps would empower water managers to focus their efforts on high risk water bodies in an attempt to prevent CyanoHABs before they occur, and/or more diligently observe those waterbodies. For this research, exploratory spatial data analysis techniques were used to identify the strongest predicators for CyanoHAB blooms based on remote sensing-derived cyanobacteria cell density values for 771 waterbodies in the Georgia Piedmont and landscape characteristics of their watersheds. In-situ datasets for cyanobacteria cell density, nutrients, temperature, and rainfall patterns are not widely available, so free gridded geospatial datasets were used as proxy variables for assessing CyanoHAB risk. For example, the percent of a watershed that is agriculture was used as a proxy for nutrient loading, and the summer precipitation within a watershed was used as a proxy for water quiescence. Cyanobacteria cell density values were calculated using atmospherically corrected images from the European Space Agency’s Sentinel-2A satellite and multispectral instrument sensor at a 10-meter ground resolution. Seventeen explanatory variables were calculated for each watershed utilizing the multi-petabyte geospatial catalogs available within the Google Earth Engine cloud computing interface. The seventeen variables were then used in a multiple linear regression model, and the strongest predictors of cyanobacteria cell density were selected for the final regression model. The seventeen explanatory variables included land cover composition, winter and summer temperature and precipitation data, topographic derivatives, vegetation index anomalies, and soil characteristics. Watershed maximum summer temperature, percent agriculture, percent forest, percent impervious, and waterbody area emerged as the strongest predictors of cyanobacteria cell density with an adjusted R-squared value of 0.31 and a p-value ~ 0. The final regression equation was used to make a normalized cyanobacteria cell density index, and a Jenks Natural Break classification was used to assign waterbodies designations of low, medium, or high risk. Of the 771 waterbodies, 24.38% were low risk, 37.35% were medium risk, and 38.26% were high risk. This study showed that there are significant relationships between free geospatial datasets representing summer maximum temperatures, nutrient loading associated with land use and land cover, and the area of a waterbody with cyanobacteria cell density. This data analytics approach to CyanoHAB risk assessment corroborated the literature-established environmental triggers for CyanoHABs, and presents a novel approach for CyanoHAB risk mapping in waterbodies across the greater southeastern United States.

Keywords: cyanobacteria, land use/land cover, remote sensing, risk mapping

Procedia PDF Downloads 211