39 research outputs found

    Motivating change: An Interactive journey in sustainability in environmental concerns

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    Despite the grave environmental issues facing the world, little is being done to educate our future generation of consumers on resource consumption and waste generation. There is a need for major change in the approach to education about sustainability. In the classroom, environmental education has been presented statically through traditional teaching methods. Environmental education is evolving to include information on how a person\u27s efforts and behavior can affect global change. However, changes in education are not happening as rapidly as the deterioration of the environment. The sustainability of the environment requires action and reaction, therefore it requires a more interactive approach to education. Can education through interactivity result in major changes? Can the inclusion of computer graphics as an alternative approach to education promote and motivate change in a person\u27s behavior in relation to the environment? This thesis is an exploration of the role Computer Graphics can play in environmental education. It is divided into two main components, Design Center and Action Toolkit. Through interactive engagement of the user this thesis offers experiential learning that successfully communicates the issue of sustainability of the environment, creating the opportunity to develop a lasting change in their daily behavior

    Is the POLST Model Desirable for Florida?

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    Florida has one ofthe largest and most rapidly growing elderly populations in the nation. Although advances in medicine are allowing physicians to extend the lives of elderly patients, advances must simultaneously be made in the end-of-life care arena to ensure that the comfort and quality of life of elderly patients is maintained. This paper argues that use of a Physician Orders for Life Sustaining Treatment (POLST) form in Florida would be effective in increasing the accuracy oftranslating patients’ end-of-life wishes into treatment orders, in ensuring the consistency of treatment across settings, and in improving health care provider compliance with patient preferences. It will be demonstrated that present concerns in Florida are essentially the same as those which previously existed in other states that have successfully implemented POLST programs

    Selective inhibition of protein secretion by abrogating receptor–coat interactions during ER export

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    Protein secretion is an essential process that drives cell growth, movement, and commu-nication. Protein traffic within the secretory pathway occurs via transport intermediatesthat bud from one compartment and fuse with a downstream compartment to delivertheir contents. Here, we explore the possibility that protein secretion can be selectivelyinhibited by perturbing protein–protein interactions that drive capture into transportvesicles. Human proprotein convertase subtilisin/kexin type 9 (PCSK9) is a determi-nant of cholesterol metabolism whose secretion is mediated by a specific cargo adaptorprotein, SEC24A. We map a series of protein–protein interactions between PCSK9, itsendoplasmic reticulum (ER) export receptor SURF4, and SEC24A that mediate secre-tion of PCSK9. We show that the interaction between SURF4 and SEC24A can beinhibited by 4-phenylbutyrate (4-PBA), a small molecule that occludes a cargo-bindingdomain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected.We propose that selective small-molecule inhibition of cargo recognition by SEC24 is apotential therapeutic intervention for atherosclerosis and other diseases that are modu-lated by secreted proteins

    Selective inhibition of protein secretion by abrogating receptor–coat interactions during ER export

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    Protein secretion is an essential process that drives cell growth, movement, and commu-nication. Protein traffic within the secretory pathway occurs via transport intermediatesthat bud from one compartment and fuse with a downstream compartment to delivertheir contents. Here, we explore the possibility that protein secretion can be selectivelyinhibited by perturbing protein–protein interactions that drive capture into transportvesicles. Human proprotein convertase subtilisin/kexin type 9 (PCSK9) is a determi-nant of cholesterol metabolism whose secretion is mediated by a specific cargo adaptorprotein, SEC24A. We map a series of protein–protein interactions between PCSK9, itsendoplasmic reticulum (ER) export receptor SURF4, and SEC24A that mediate secre-tion of PCSK9. We show that the interaction between SURF4 and SEC24A can beinhibited by 4-phenylbutyrate (4-PBA), a small molecule that occludes a cargo-bindingdomain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected.We propose that selective small-molecule inhibition of cargo recognition by SEC24 is apotential therapeutic intervention for atherosclerosis and other diseases that are modu-lated by secreted proteins

    Nitric oxide production and antioxidant function during viral infection of the coccolithophore Emiliania huxleyi

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    Emiliania huxleyi is a globally important marine phytoplankton that is routinely infected by viruses. Understanding the controls on the growth and demise of E. huxleyi blooms is essential for predicting the biogeochemical fate of their organic carbon and nutrients. In this study, we show that the production of nitric oxide (NO), a gaseous, membrane-permeable free radical, is a hallmark of early-stage lytic infection in E. huxleyi by Coccolithoviruses, both in culture and in natural populations in the North Atlantic. Enhanced NO production was detected both intra- and extra-cellularly in laboratory cultures, and treatment of cells with an NO scavenger significantly reduced viral production. Pre-treatment of exponentially growing E. huxleyi cultures with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) prior to challenge with hydrogen peroxide (H2O2) led to greater cell survival, suggesting that NO may have a cellular antioxidant function. Indeed, cell lysates generated from cultures treated with SNAP and undergoing infection displayed enhanced ability to detoxify H2O2. Lastly, we show that fluorescent indicators of cellular ROS, NO, and death, in combination with classic DNA- and lipid-based biomarkers of infection, can function as real-time diagnostic tools to identify and contextualize viral infection in natural E. huxleyi blooms

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

    Behavioral responses of terrestrial mammals to COVID-19 lockdowns

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    DATA AND MATERIALS AVAILABILITY : The full dataset used in the final analyses (33) and associated code (34) are available at Dryad. A subset of the spatial coordinate datasets is available at Zenodo (35). Certain datasets of spatial coordinates will be available only through requests made to the authors due to conservation and Indigenous sovereignty concerns (see table S1 for more information on data use restrictions and contact information for data requests). These sensitive data will be made available upon request to qualified researchers for research purposes, provided that the data use will not threaten the study populations, such as by distribution or publication of the coordinates or detailed maps. Some datasets, such as those overseen by government agencies, have additional legal restrictions on data sharing, and researchers may need to formally apply for data access. Collaborations with data holders are generally encouraged, and in cases where data are held by Indigenous groups or institutions from regions that are under-represented in the global science community, collaboration may be required to ensure inclusion.COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.The Radboud Excellence Initiative, the German Federal Ministry of Education and Research, the National Science Foundation, Serbian Ministry of Education, Science and Technological Development, Dutch Research Council NWO program “Advanced Instrumentation for Wildlife Protection”, Fondation Segré, RZSS, IPE, Greensboro Science Center, Houston Zoo, Jacksonville Zoo and Gardens, Nashville Zoo, Naples Zoo, Reid Park Zoo, Miller Park, WWF, ZCOG, Zoo Miami, Zoo Miami Foundation, Beauval Nature, Greenville Zoo, Riverbanks zoo and garden, SAC Zoo, La Passarelle Conservation, Parc Animalier d’Auvergne, Disney Conservation Fund, Fresno Chaffee zoo, Play for nature, North Florida Wildlife Center, Abilene Zoo, a Liber Ero Fellowship, the Fish and Wildlife Compensation Program, Habitat Conservation Trust Foundation, Teck Coal, and the Grand Teton Association. The collection of Norwegian moose data was funded by the Norwegian Environment Agency, the German Ministry of Education and Research via the SPACES II project ORYCS, the Wyoming Game and Fish Department, Wyoming Game and Fish Commission, Bureau of Land Management, Muley Fanatic Foundation (including Southwest, Kemmerer, Upper Green, and Blue Ridge Chapters), Boone and Crockett Club, Wyoming Wildlife and Natural Resources Trust, Knobloch Family Foundation, Wyoming Animal Damage Management Board, Wyoming Governor’s Big Game License Coalition, Bowhunters of Wyoming, Wyoming Outfitters and Guides Association, Pope and Young Club, US Forest Service, US Fish and Wildlife Service, the Rocky Mountain Elk Foundation, Wyoming Wild Sheep Foundation, Wild Sheep Foundation, Wyoming Wildlife/Livestock Disease Research Partnership, the US National Science Foundation [IOS-1656642 and IOS-1656527, the Spanish Ministry of Economy, Industry and Competitiveness, and by a GRUPIN research grant from the Regional Government of Asturias, Sigrid Rausing Trust, Batubay Özkan, Barbara Watkins, NSERC Discovery Grant, the Federal Aid in Wildlife Restoration act under Pittman-Robertson project, the State University of New York, College of Environmental Science and Forestry, the Ministry of Education, Youth and Sport of the Czech Republic, the Ministry of Agriculture of the Czech Republic, Rufford Foundation, an American Society of Mammalogists African Graduate Student Research Fund, the German Science Foundation, the Israeli Science Foundation, the BSF-NSF, the Ministry of Agriculture, Forestry and Food and Slovenian Research Agency (CRP V1-1626), the Aage V. Jensen Naturfond (project: Kronvildt - viden, værdier og værktøjer), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, National Centre for Research and Development in Poland, the Slovenian Research Agency, the David Shepherd Wildlife Foundation, Disney Conservation Fund, Whitley Fund for Nature, Acton Family Giving, Zoo Basel, Columbus, Bioparc de Doué-la-Fontaine, Zoo Dresden, Zoo Idaho, Kolmården Zoo, Korkeasaari Zoo, La Passarelle, Zoo New England, Tierpark Berlin, Tulsa Zoo, the Ministry of Environment and Tourism, Government of Mongolia, the Mongolian Academy of Sciences, the Federal Aid in Wildlife Restoration act and the Illinois Department of Natural Resources, the National Science Foundation, Parks Canada, Natural Sciences and Engineering Research Council, Alberta Environment and Parks, Rocky Mountain Elk Foundation, Safari Club International and Alberta Conservation Association, the Consejo Nacional de Ciencias y Tecnología (CONACYT) of Paraguay, the Norwegian Environment Agency and the Swedish Environmental Protection Agency, EU funded Interreg SI-HR 410 Carnivora Dinarica project, Paklenica and Plitvice Lakes National Parks, UK Wolf Conservation Trust, EURONATUR and Bernd Thies Foundation, the Messerli Foundation in Switzerland and WWF Germany, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions, NASA Ecological Forecasting Program, the Ecotone Telemetry company, the French National Research Agency, LANDTHIRST, grant REPOS awarded by the i-Site MUSE thanks to the “Investissements d’avenir” program, the ANR Mov-It project, the USDA Hatch Act Formula Funding, the Fondation Segre and North American and European Zoos listed at http://www.giantanteater.org/, the Utah Division of Wildlife Resources, the Yellowstone Forever and the National Park Service, Missouri Department of Conservation, Federal Aid in Wildlife Restoration Grant, and State University of New York, various donors to the Botswana Predator Conservation Program, data from collared caribou in the Northwest Territories were made available through funds from the Department of Environment and Natural Resources, Government of the Northwest Territories. The European Research Council Horizon2020, the British Ecological Society, the Paul Jones Family Trust, and the Lord Kelvin Adam Smith fund, the Tanzania Wildlife Research Institute and Tanzania National Parks. The Eastern Shoshone and Northern Arapahoe Fish and Game Department and the Wyoming State Veterinary Laboratory, the Alaska Department of Fish and Game, Kodiak Brown Bear Trust, Rocky Mountain Elk Foundation, Koniag Native Corporation, Old Harbor Native Corporation, Afognak Native Corporation, Ouzinkie Native Corporation, Natives of Kodiak Native Corporation and the State University of New York, College of Environmental Science and Forestry, and the Slovenia Hunters Association and Slovenia Forest Service. F.C. was partly supported by the Resident Visiting Researcher Fellowship, IMéRA/Aix-Marseille Université, Marseille. This work was partially funded by the Center of Advanced Systems Understanding (CASUS), which is financed by Germany’s Federal Ministry of Education and Research (BMBF) and by the Saxon Ministry for Science, Culture and Tourism (SMWK) with tax funds on the basis of the budget approved by the Saxon State Parliament. This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society.https://www.science.org/journal/sciencehj2023Mammal Research InstituteZoology and Entomolog

    Stimulations of HEK293TLR4 Cells with Fractionated Proteomannan Leads to the Detection of an Inhibiting Component

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    Stimulations of HEK293TLR4 Cells with Fractionated Proteomannan Leads to the Detection of an Inhibiting Componen

    Evaluation of In-Hospital Management of Inhaler Therapy for Chronic Obstructive Pulmonary Disease

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    Background: In the past decade, the number of inhaled devices approved for management of chronic obstructive pulmonary disease (COPD) has tripled. Management of at-home inhaled COPD therapy can present a problem when patients are admitted to hospital, because only a limited number of these therapies are currently included in hospital formularies and there is a lack of established interchanges. Objectives: To characterize and evaluate the appropriateness of management of patients’ before-admission inhaled therapy upon hospital admission. Methods: This retrospective chart review involved patients with COPD admitted to a tertiary care centre over a 1-year period (October 2017 to September 2018). Before-admission inhaled therapy was compared with inhalers ordered in hospital and at discharge. Inhaler device type, regimen, therapeutic class, and disease severity were used to assess the appropriateness of inpatient management. Results: The charts of 200 patients were reviewed. Of these patients, 124 (62%) were kept on the same inhaler, 43 (22%) had one or more of their inhalers discontinued, 35 (18%) had to provide their own medication, and 24 (12%) had their medication changed to a formulary equivalent. An average delay of 2.6 (standard deviation 3.2) days occurred when patients provided their own medication. Formulary substitution resulted in most patients receiving a medication from the same class (75% [18/24]); however, other aspects of therapy, such as device type (17% [4/24]), regimen (29% [7/24]) and drug combination (47% [9/19]), were not maintained. Only 55% (6/11) received an equivalent dose of inhaled corticosteroids when the medication was interchanged to a formulary inhaler. Conclusions: The majority of patients’ inhaled therapies continued unchanged upon admission to hospital, which suggests that despite the proliferation of new inhalers on the market, their use is still limited. For patients who did require interchange to formulary inhalers, maintenance of the same regimen, device, and combination product was rare. Provision of the medication supply by patients themselves often resulted in a delay in therapy. RÉSUMÉ Contexte : Au cours des dix dernières années, le nombre de dispositifs d’inhalation approuvés pour gérer la maladie pulmonaire obstructive chronique (MPOC) a été multiplié par trois. La gestion de la thérapie à domicile de la MPOC peut présenter un problème lors de l’admission à l’hôpital, car seul un nombre limité de ces thérapies est actuellement inclus dans la pharmacopée des hôpitaux et les tableaux d’équivalence des médicaments font défaut. Objectifs : Au moment de l’admission à l’hôpital, définir et évaluer l’adéquation dentre l’inhalothérapie des patients avant leur admission et celle offert à l’hôpital. Méthodes : Cet examen rétrospectif des dossiers concernait des patients atteints d’une MPOC ayant été admis dans un centre de soins tertiaires sur une période d’un an (d’octobre 2017 à septembre 2018). Il portait sur la comparaison entre l’inhalothérapie avant l’admission et les inhalateurs commandés à l’hôpital et au moment du congé. Le type de dispositif d’inhalation, le régime, la classe thérapeutique et la gravité de la maladie ont servi à évaluer la pertinence de la gestion de l’inhalothérapie des patients hospitalisés. Résultats : L’examen portait sur les dossiers de 200 patients. De ceux-ci, 124 (62 %) ont gardé le même inhalateur; 43 (22 %) ont vu la suppression d’au moins un inhalateur; 35 (18 %) ont dû fournir leurs propres médicaments; et les médicaments de 24 (12 %) d’entre eux ont été remplacés par un équivalent de la pharmacopée. Les investigateurs ont observé un retard moyen de 2,6 jours (écart type 3,2) lorsque les patients fournissaient leurs propres médicaments. La substitution par des médicaments de la pharmacopée a conduit la plupart des patients à en recevoir un de la même classe (75 % [18/24]); cependant, d’autres aspects de la thérapie n’ont pas été maintenus, comme le type de dispositif (17 % [4/24]), le régime (29 % [7/24]) et la combinaison de médicaments (47 % [9/19]). Seuls 55 % (6/11) ont reçu une dose équivalente de corticostéroïdes en inhalation, lors du remplacement du médicament par un inhalateur de la pharmacopée. Conclusions : La majorité des inhalothérapies des patients sont restées inchangées au moment de l’admission à l’hôpital, ce qui laisse entendre que, malgré la prolifération de nouveaux inhalateurs sur le marché, leur utilisation est encore limitée. Pour les patients qui nécessitaient le remplacement par un inhalateur de la pharmacopée, le maintien du même régime, du même dispositif et du même produit de combinaison était rare. L’approvisionnement en médicaments par les patients eux-mêmes entraînait souvent un retard dans la thérapie.
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