1,622 research outputs found

    New Kansas Roots for Students: building cultural competency through the Nicodemus Project

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    Five-member panel (two faculty members representing two supporting professional disciplines; Nicodemus resident and on campus resource; a MLA graduate student; and a graduate planner) recapping how the Parks for the People/Nicodemus project transformed students and community members. Short segments of video demonstrating student learning outcomes associated with diversity and collaboration will be introduced. This project won the CECD Engagement Award from Kansas State University in 2013. (270-word abstract uploaded

    Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus ι-synuclein and β-amyloid aggregates

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    Transcellular propagation of protein aggregate “seeds” has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct interaction with modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs). Varying the GAG length and sulfation patterns, we next conducted competition studies with heparin derivatives in cell-based assays. Tau aggregates required a precise GAG architecture with defined sulfate moieties in the N- and 6-O-positions, whereas the binding of α-synuclein and Aβ aggregates was less stringent. To determine the genes required for aggregate uptake, we used CRISPR/Cas9 to individually knock out the major genes of the HSPG synthesis pathway in HEK293T cells. Knockouts of the extension enzymes exostosin 1 (EXT1), exostosin 2 (EXT2), and exostosin-like 3 (EXTL3), as well as N-sulfotransferase (NDST1) or 6-O-sulfotransferase (HS6ST2) significantly reduced tau uptake, consistent with our biochemical findings, and knockouts of EXT1, EXT2, EXTL3, or NDST1, but not HS6ST2 reduced α-synuclein uptake. In summary, tau aggregates display specific interactions with HSPGs that depend on GAG length and sulfate moiety position, whereas α-synuclein and Aβ aggregates exhibit more flexible interactions with HSPGs. These principles may inform the development of mechanism-based therapies to block transcellular propagation of amyloid protein–based pathologies

    Powerful Relationships in Leadership: A Collection of Modern Leadership Insights

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    Powerful Relationships in Leadership caters to front runners of the leadership world who are looking for fresh perspectives into how to properly organize and create trailblazing organizations. This book is a collection of articles on aspects of leading. It separates itself from other management texts by offering perceptions of entry level personnel. It is our hope that you will begin to appreciate how entry level personnel view management and their role in guiding administrators.https://openriver.winona.edu/leadershipeducationbooks/1001/thumbnail.jp

    Doctor of Education Newsletter 2020

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    WSU Doctor of Education Cohort 2020 This newsletter was created by the second Education Doctorate graduate student cohort 2020.https://openriver.winona.edu/educationeddnewsletters/1001/thumbnail.jp

    From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses

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    Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies

    Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds:the FiCTION three-arm RCT

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    Background Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. Objectives The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. Design This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. Setting This trial was set in primary dental care in Scotland, England and Wales. Participants Participants were NHS patients aged 3–7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. Interventions Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). Main outcome measures The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. Results A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8–36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was –0.02 (97.5% confidence interval –0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval –0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. Conclusions There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period

    Bicuspid and unicuspid aortic valves: Different phenotypes of the same disease? Insight from the GenTAC Registry

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    BackgroundUnicuspid aortic valve (UAV) is a rare disorder, often difficult to distinguish from bicuspid aortic valve (BAV). BAV and UAV share valve pathology such as the presence of a raphe, leaflet fusion, aortic stenosis, aortic regurgitation, and/or ascending aortic dilatation, but a comprehensive echocardiographic comparison of patients with UAV and BAV has not been previously performed.MethodsWe investigated UAV and BAV patients at an early stage of disease included in GenTAC, a national registry of genetically related aortic aneurysms and associated cardiac conditions. Clinical and echocardiographic data from the GenTAC Registry were compared between 17 patients with UAV and 17 matched‐controls with BAV.ResultsBaseline characteristics including demographics, clinical findings including family history of BAV and aortic aneurysm/coarctation, and echocardiographic variables were similar between BAV and UAV patients; aortic stenosis was more common and more severe in patients with UAV. This was evidenced by higher mean and peak gradient, smaller aortic valve area, and more advanced valvular degeneration (all P < .05). There were no significant differences in aortic dimensions, with a similar pattern of enlargement of the ascending aorta.ConclusionsThe similar baseline characteristics with more accelerated aortic valve degeneration and stenosis suggest that UAV represents an extreme in the spectrum of BAV syndromes. Therefore, it is reasonable to consider application of recommendations for the management of patients with BAV to those with the rarer UAV.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139976/1/chd12520.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139976/2/chd12520_am.pd

    ProPIG - Organic pig health, welfare and environmental impact across Europe

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    Organic production is perceived by consumers as being superior in animal welfare and sustainability and the demand for organic pork products is slowly increasing. Within the past ten years a variety of husbandry and management systems have been developed across the EU, ranging from farms with pigs outdoors all year round using local breeds to farms with housed pigs having concrete outside runs and using conventional breeds (CorePIG, Rousing et al, 2011). So far, mainly clinical parameters have been used to describe the health situation on organic pig farms, identifying some key problems, such as weaning diarrhoea and piglet mortality. Organic pig production is - amongst others - characterised through a holistic approach based on the EU Regulation (EC) No 834/2007 and the IFOAM principles: ‘health, ecology, fairness and care’. This clearly states that health is more than absence of clinical symptoms and, the relation between animals and their environment is identified: ‘Health’ is defined as ‘the wholeness and integrity of living systems. It is not simply the absence of illness, but the maintenance of physical, mental, social and ecological well-being’ (IFOAM; 2006). Concepts of animal welfare include physical and mental welfare as well as the concept of naturalness (Fraser 2003), which is often interpreted as the ability to perform natural behaviour. Verhoog et al (2003) describe three main approaches within organic agriculture’s concept of nature and naturalness: the no-chemicals approach, the agro-ecology approach and the integrity approach. Applying those concepts to organic pig production can highlight potential conflicts: outdoor systems are perceived as the optimal housing system for pigs, as they allow natural behaviour such as rooting. However, this behaviour can cause damage to the grass cover and furthermore the manure fate in outdoor areas needs to be considered. A few studies on outdoor pig production have shown a clear N and P surplus and a high degree of distribution heterogeneity in outdoor areas, increasing the risk of N and P losses (Watson et al. 2003). Robust and competitive organic pig production needs to encompass low environmental impacts and good animal health and welfare. So far few studies have quantified both aspects in different pig husbandry systems. In addition, the theory that improving animal health and welfare reduces environmental impacts through decreased medicine use, improved growth rate and feed conversion efficiency has still to be verified. The aim of the CoreOrganic2 project ProPIG (2011-2014; carried out in eight European countries) is to examine the relationship between health, welfare and environmental impact. On-farm assessment protocols will be carried out on 75 farms in three pig husbandry systems (outdoor, partly outdoor, indoor with concrete outside run). Environmental impact will be assessed using both Life Cycle Assessment and calculations of nutrient balances at farm and outdoor area level. Animal health and welfare will be evaluated from animal based parameters including clinical and selected behavioural parameters. Results will be fed back and used by the farmers to decide farm specific goals and strategies to achieve these goals. As an outcome, all farms will create their individual health, welfare and environmental plan, which will be reviewed after one year to allow continuous development. This will provide the opportunity not only to investigate, but also improve the influence of organic pig farming systems on animal welfare and environmental impact. This fulfils the fourth IFOAM principle of care: ‘Organic Agriculture should be managed in a precautionary and responsible manner to protect the health and well-being of current and future generations and the environment’ (IFOAM, 2006)

    Imported Lassa Fever, Pennsylvania, USA, 2010

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    We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred
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