25 results on '"Schmidt, Chris"'
Search Results
2. The prevalence of onchocerciasis in Africa and Yemen, 2000-2018: a geospatial analysis.
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Schmidt, Chris A., Cromwell, Elizabeth A., Hill, Elex, Donkers, Katie M., Schipp, Megan F., Johnson, Kimberly B., Pigott, David M., LBD 2019 Neglected Tropical Diseases Collaborators, Abbas, Jaffar, Adekanmbi, Victor, Adetokunboh, Olatunji O., Ahmed, Muktar Beshir, Alanezi, Fahad Mashhour, Alanzi, Turki M., Alipour, Vahid, Andrei, Catalina Liliana, Andrei, Tudorel, Anvari, Davood, Appiah, Seth Christopher Yaw, and Aqeel, Muhammad
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ONCHOCERCIASIS , *ONCHOCERCA volvulus , *SKIN diseases , *SIMULIIDAE , *VISION disorders - Abstract
Background: Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission.Methods: A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions.Results: As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan.Conclusions: Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. Fundamental fertiliser guidelines.
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Schmidt, Chris
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PLANT spacing , *SOIL chemistry - Abstract
The article delves into the rationale behind using fertilizers in commercial crop production, likening the process to medical diagnosis and treatment. Topics include soil analysis emphasizing the 4R-Nutrient-Stewardship framework, and crafting a fertiliser plan based on soil chemistry, crop type, and nutrient uptake mechanisms.
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- 2024
4. Advances in the REDCAT software package.
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Schmidt, Chris, Irausquin, Stephanie J., and Valafar, Homayoun
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Background: Residual Dipolar Couplings (RDCs) have emerged in the past two decades as an informative source of experimental restraints for the study of structure and dynamics of biological macromolecules and complexes. The REDCAT software package was previously introduced for the analysis of molecular structures using RDC data. Here we report additional features that have been included in this software package in order to expand the scope of its analyses. We first discuss the features that enhance REDCATs user-friendly nature, such as the integration of a number of analyses into one single operation and enabling convenient examination of a structural ensemble in order to identify the most suitable structure. We then describe the new features which expand the scope of RDC analyses, performing exercises that utilize both synthetic and experimental data to illustrate and evaluate different features with regard to structure refinement and structure validation. Results: We establish the seamless interaction that takes place between REDCAT, VMD, and Xplor-NIH in demonstrations that utilize our newly developed REDCAT-VMD and XplorGUI interfaces. These modules enable visualization of RDC analysis results on the molecular structure displayed in VMD and refinement of structures with Xplor-NIH, respectively. We also highlight REDCAT’s Error-Analysis feature in reporting the localized fitness of a structure to RDC data, which provides a more effective means of recognizing local structural anomalies. This allows for structurally sound regions of a molecule to be identified, and for any refinement efforts to be focused solely on locally distorted regions. Conclusions: The newly engineered REDCAT software package, which is available for download via the WWW from http://ifestos.cse.sc.edu, has been developed in the Object Oriented C++ environment. Our most recent enhancements to REDCAT serve to provide a more complete RDC analysis suite, while also accommodating a more user-friendly experience, and will be of great interest to the community of researchers and developers since it hides the complications of software development. [ABSTRACT FROM AUTHOR]
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- 2013
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5. Treatment of non-resectable hepatocellular carcinoma with autologous tumor-pulsed dendritic cells.
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Ladhams, Andrew, Schmidt, Chris, Sing, Garwin, Butterworth, Lesley, Fielding, George, Tesar, Paul, Strong, Russell, Leggett, Barbara, Powell, Lawrie, Maddern, Guy, Ellem, Kay, and Cooksley, Graham
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LIVER cancer , *DENDRITIC cells , *IMMUNOTHERAPY , *TUMOR antigens , *THERAPEUTICS - Abstract
Abstract Background: The response of hepatocellular carcinoma (HCC) to therapy is often disappointing and new modalities of treatment are clearly needed. Active immunotherapy based on the injection of autologous dendritic cells (DC) co-cultured ex vivo with tumor antigens has been used in pilot studies in various malignancies such as melanoma and lymphoma with encouraging results. Methods: In the present paper, the preparation and exposure of patient DC to autologous HCC antigens and re-injection in an attempt to elicit antitumor immune responses are described. Results: Therapy was given to two patients, one with hepatitis C and one with hepatitis B, who had large, multiple HCC and for whom no other therapy was available. No significant side-effects were observed. The clinical course was unchanged in one patient, who died a few months later. The other patient, whose initial prognosis was considered poor, is still alive and well more than 3 years later with evidence of slowing of tumor growth based on organ imaging. Conclusions: It is concluded that HCC may be a malignancy worthy of DC trials and sufficient details in the present paper are given for the protocol to be copied or modified. [ABSTRACT FROM AUTHOR]
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- 2002
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6. Adult Understanding of Spontaneous Attention-Directing Events: What Does Gesture Contribute?
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Schmidt, Chris L.
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GESTURE , *ATTENTION , *PSYCHOLOGY of students - Abstract
Studies the contribution of gestures to the understanding of spontaneous attention-directing events focusing on some aspects of the surroundings among university students. Details on the Shared Attention Mechanism; Discussions on unheard speech; Relationship between gesture and focus; Role of gestures and speech in providing attentional focus information.
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- 1999
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7. The Best Sex Ever.
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Schmidt, Chris, Cavella, Joey, Griscom, Rufus, Martin, Ross, and Sharkey, Lorelei
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HUMAN sexuality in motion pictures - Abstract
Presents a list of favorite movie sex scenes by sexperts. 'A Room With a View'; 'Microcosmos'; 'The Ice Storm'; 'The Hunger'; 'Skin Deep'.
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- 2002
8. Effects of desiccation stress on adult female longevity in <italic>Aedes aegypti</italic> and <italic>Ae. albopictus</italic> (Diptera: Culicidae): results of a systematic review and pooled survival analysis.
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Schmidt, Chris A., Comeau, Genevieve, Monaghan, Andrew J., Williamson, Daniel J., and Ernst, Kacey C.
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AEDES albopictus , *DEHYDRATION , *AEDES aegypti , *DIPTERA , *SURVIVALISM , *PHYSIOLOGY - Abstract
Background: Transmission dynamics of mosquito-borne viruses such as dengue, Zika and chikungunya are affected by the longevity of the adult female mosquito. Environmental conditions influence the survival of adult female
Aedes mosquitoes, the primary vectors of these viruses. While the association of temperature withAedes mortality has been relatively well-explored, the role of humidity is less established. The current study's goals were to compile knowledge of the influence of humidity on adult survival in the important vector speciesAedes aegypti andAe. albopictus , and to quantify this relationship while accounting for the modifying effect of temperature. Methods: We performed a systematic literature review to identify studies reporting experimental results informing the relationships among temperature, humidity and adult survival inAe. aegypti andAe. albopictus . Using a novel simulation approach to harmonize disparate survival data, we conducted pooled survival analyses via stratified and mixed effects Cox regression to estimate temperature-dependent associations between humidity and mortality risk for these species across a broad range of temperatures and vapor pressure deficits. Results: After screening 1517 articles, 17 studies (one in semi-field and 16 in laboratory settings) met inclusion criteria and collectively reported results for 192 survival experiments. We review and synthesize relevant findings from these studies. Our stratified model estimated a strong temperature-dependent association of humidity with mortality in both species, though associations were not significant forAe. albopictus in the mixed effects model. Lowest mortality risks were estimated around 27.5 °C and 21.5 °C forAe. aegypti andAe. albopictus , respectively, and mortality increased non-linearly with decreasing humidity.Aedes aegypti had a survival advantage relative toAe. albopictus in the stratified model under most conditions, but species differences were not significant in the mixed effects model. Conclusions: Humidity is associated with mortality risk in adult femaleAe. aegypti in controlled settings. Data are limited at low humidities, temperature extremes, and forAe. albopictus , and further studies should be conducted to reduce model uncertainty in these contexts. Desiccation is likely an important factor inAedes population dynamics and viral transmission in arid regions. Models ofAedes -borne virus transmission may be improved by more comprehensively representing humidity effects. [ABSTRACT FROM AUTHOR]- Published
- 2018
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9. Multimodal Wildland Fire Smoke Detection.
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Bhamra, Jaspreet Kaur, Anantha Ramaprasad, Shreyas, Baldota, Siddhant, Luna, Shane, Zen, Eugene, Ramachandra, Ravi, Kim, Harrison, Schmidt, Chris, Arends, Chris, Block, Jessica, Perez, Ismael, Crawl, Daniel, Altintas, Ilkay, Cottrell, Garrison W., and Nguyen, Mai H.
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WILDFIRES , *FIRE detectors , *WILDFIRE prevention , *SMOKE , *DEEP learning , *OPTICAL images , *WILDFIRE risk - Abstract
Research has shown that climate change creates warmer temperatures and drier conditions, leading to longer wildfire seasons and increased wildfire risks in the United States. These factors have, in turn, led to increases in the frequency, extent, and severity of wildfires in recent years. Given the danger posed by wildland fires to people, property, wildlife, and the environment, there is an urgent need to provide tools for effective wildfire management. Early detection of wildfires is essential to minimizing potentially catastrophic destruction. To that end, in this paper, we present our work on integrating multiple data sources into SmokeyNet, a deep learning model using spatiotemporal information to detect smoke from wildland fires. We present Multimodal SmokeyNet and SmokeyNet Ensemble for multimodal wildland fire smoke detection using satellite-based fire detections, weather sensor measurements, and optical camera images. An analysis is provided to compare these multimodal approaches to the baseline SmokeyNet in terms of accuracy metrics, as well as time-to-detect, which is important for the early detection of wildfires. Our results show that incorporating weather data in SmokeyNet improves performance numerically in terms of both F1 and time-to-detect over the baseline with a single data source. With a time-to-detect of only a few minutes, SmokeyNet can be used for automated early notification of wildfires, providing a useful tool in the fight against destructive wildfires. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Differences in Longevity and Temperature-Driven Extrinsic Incubation Period Correlate with Varying Dengue Risk in the Arizona–Sonora Desert Region.
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Ernst, Kacey C., Walker, Kathleen R., Castro-Luque, A Lucia, Schmidt, Chris, Joy, Teresa K., Brophy, Maureen, Reyes-Castro, Pablo, Díaz-Caravantes, Rolando Enrique, Encinas, Veronica Ortiz, Aguilera, Alfonso, Gameros, Mercedes, Cuevas Ruiz, Rosa Elena, Hayden, Mary H., Alvarez, Gerardo, Monaghan, Andrew, Williamson, Daniel, Arnbrister, Josh, Gutiérrez, Eileen Jeffrey, Carrière, Yves, and Riehle, Michael A.
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MOSQUITO vectors , *DESERTS , *DENGUE , *MOSQUITO control , *AEDES aegypti , *DENGUE viruses , *LONGEVITY - Abstract
Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector–human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona–Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Molecular phylogenetics and diversification of trap-jaw ants in the genera Anochetus and Odontomachus (Hymenoptera: Formicidae).
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Larabee, Fredrick J., Fisher, Brian K., Schmidt, Chris A., Matos-Maraví, Pável, Janda, Milan, and Suarez, Andrew V.
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INSECT phylogeny , *INSECT diversity , *MOLECULAR phylogeny , *RIBOSOMAL RNA , *GEOGRAPHICAL distribution of insects , *ODONTOMACHUS - Abstract
Ants in the genera Anochetus and Odontomachus belong to one of the largest clades in the subfamily Ponerinae, and are one of four lineages of ants possessing spring-loaded “trap-jaws.” Here we present results from the first global species-level molecular phylogenetic analysis of these trap-jaw ants, reconstructed from one mitochondrial, one ribosomal RNA, and three nuclear protein-coding genes. Bayesian and likelihood analyses strongly support reciprocal monophyly for the genera Anochetus and Odontomachus . Additionally, we found strong support for seven trap-jaw ant clades (four in Anochetus and three in Odontomachus ) mostly concordant with geographic distribution. Ambiguity remains concerning the closest living non-trap-jaw ant relative of the Anochetus + Odontomachus clade, but Bayes factor hypothesis testing strongly suggests that trap-jaw ants evolved from a short mandible ancestor . Ponerine trap-jaw ants originated in the early Eocene (52.5 Mya) in either South America or Southeast Asia, where they have radiated rapidly in the last 30 million years, and subsequently dispersed multiple times to Africa and Australia. These results will guide future taxonomic work on the group and act as a phylogenetic framework to study the macroevolution of extreme ant mouthpart specialization. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Thyroid hormone supplementation improves bovine embryo development in vitro.
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Ashkar, Fazl A., Semple, Esther, Schmidt, Chris H., John, Elizabeth St., Bartlewski, Pawel M., and King, W. A.
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THYROID hormones , *REPRODUCTIVE technology , *EMBRYOS , *CATTLE embryos ,CATTLE development - Abstract
BACKGROUND: Early embryo development (EED) forms the basis of assisted reproductive technologies (ARTs), which are used to treat human infertility and to propagate other mammalian species. Thyroid hormones (THs) play an important role in the post-implantation development of the embryo in mammals; however, the effects of THs on pre-attachment embryos are not known. Currently utilized in-vitro embryo production media are devoid of THs and hence our main objective was to examine whether THs affected EED in a bovine model. [ABSTRACT FROM PUBLISHER]
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- 2010
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13. Phylogeny, scaling, and the generation of extreme forces in trap-jaw ants.
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Spagna, Joseph C., Vakis, Antonis I., Schmidt, Chris A., Patek, Sheila N., Xudong Zhang, Tsutsui, Neil D., and Suarez, Andrew V.
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PHYLOGENY , *ANTS , *JAWS , *MANDIBLE , *HYMENOPTERA - Abstract
Trap-jaw ants of the genus Odontomachus produce remarkably fast predatory strikes. The closing mandibles of Odontomachus bauri, for example, can reach speeds of over 60 m s-1. They use these jaw strikes for both prey capture and locomotion — by striking hard surfaces, they can launch themselves into the air. We tested the hypothesis that morphological variation across the genus is correlated with differences in jaw speeds and accelerations. We video-recorded jaw-strikes at 70 000-100 000 frames s-1 to measure these parameters and to model force production. Differences in mean speeds ranged from 35.9±7.7 m s-1 for O. chelifer, to 48.8±8.9 m s-1 for O. clarus desertorum. Differences in species' accelerations and jaw sizes resulted in maximum strike forces in the largest ants (O. chelifer) that were four times those generated by the smallest ants (O. ruginodis). To evaluate phylogenetic effects and make statistically valid comparisons, we developed a phylogeny of all sampled Odontomachus species and seven outgroup species (19 species total) using four genetic loci. Jaw acceleration and jaw-scaling factors showed significant phylogenetic non-independence, whereas jaw speed and force did not. Independent contrast (IC) values were used to calculate scaling relationships for jaw length, jaw mass and body mass, which did not deviate significantly from isometry. IC regression of angular acceleration and body size show an inverse relationship, but combined with the isometric increase in jaw length and mass results in greater maximum strike forces for the largest Odontomachus species. Relatively small differences (3%) between IC and species-mean based models suggest that any deviation from isometry in species' force production may be the result of recent selective evolution, rather than deep phylogenetic signal. [ABSTRACT FROM AUTHOR]
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- 2008
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14. Farm-scale evaluation of the impacts of transgenic cotton on biodiversity, pesticide use, and yield.
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Cattaneo, Manda G., Yafuso, Christine, Schmidt, Chris, Cho-Ying Huang, Rahman, Magfurar, Olson, Carl, Ellers-Kirk, Christa, Orr, Barron J., Marsh, Stuart E., Antilla, Larry, Dutilleul, Pierre, and Carrière, Yves
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BIODIVERSITY , *AGRICULTURAL intensification , *COTTON , *PESTICIDES , *HERBICIDES - Abstract
Higher yields and reduced pesticide impacts are needed to mitigate the effects of agricultural intensification. A 2-year farm-scale evaluation of 81 commercial fields in Arizona show that use of transgenic Bacillus thuringiensis (Bt) cotton reduced insecticide use, whereas transgenic cotton with Bt protein and herbicide resistance (BtHr) did not affect herbicide use. Transgenic cotton had higher yield than nontransgenic cotton for any given number of insecticide applications. However, nontransgenic, Bt and BtHr cotton had similar yields overall, largely because higher insecticide use with nontransgenic cotton improved control of key pests. Unlike Bt and BtHr cotton, insecticides reduced the diversity of nontarget insects. Several other agronomic and ecological factors also affected biodiversity. Nevertheless, pairwise comparisons of diversity of nontarget insects in cotton fields with diversity in adjacent noncultivated sites revealed similar effects of cultivation of transgenic and nontransgenic cotton on biodiversity. The results indicate that impacts of agricultural intensification can be reduced when replacement of broad-spectrum insecticides by narrow-spectrum Bt crops does not reduce control of pests not affected by Bt crops. [ABSTRACT FROM AUTHOR]
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- 2006
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15. Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning.
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Cromwell, Elizabeth A., Osborne, Joshua C. P., Unnasch, Thomas R., Basáñez, Maria-Gloria, Gass, Katherine M., Barbre, Kira A., Hill, Elex, Johnson, Kimberly B., Donkers, Katie M., Shirude, Shreya, Schmidt, Chris A., Adekanmbi, Victor, Adetokunboh, Olatunji O., Afarideh, Mohsen, Ahmadpour, Ehsan, Ahmed, Muktar Beshir, Akalu, Temesgen Yihunie, Al-Aly, Ziyad, Alanezi, Fahad Mashhour, and Alanzi, Turki M.
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ONCHOCERCIASIS , *RECEIVER operating characteristic curves , *REGRESSION trees , *ENVIRONMENTAL indicators - Abstract
Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify. Author summary: As of 2018, it was unknown if onchocerciasis transmission occurred among approximately 2 400 implementation units (IUs; typically, second administrative-level units, such as districts) considered potentially endemic. These IUs have either never been surveyed for onchocerciasis or historical data are not sufficient to define contemporary endemicity status. Given the large number of IUs for which baseline data collection is likely required to achieve continental elimination, there is a need to prioritise areas for surveys to ensure that those suitable for endemic transmission, and therefore potentially eligible for mass drug administration, are able to initiate interventions as soon as possible. We used boosted regression trees to predict environmental suitability for onchocerciasis, with corresponding measures of uncertainty. We summarized the fine scale spatial predictions at the IU level by using receiver operating characteristic (ROC) curve analysis to identify a threshold that maximized agreement with the occurrence locations to identify IUs that may warrant prioritisation for mapping surveys. This analysis suggests that approximately half of the IUs considered for surveys could be classified as environmentally suitable for onchocerciasis. In order to develop an elimination strategy, many national onchocerciasis elimination programmes (NOEPs) need a mechanism to synthesise historical data to define priority areas for surveys. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Genomic estimation of complex traits reveals ancient maize adaptation to temperate North America.
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Swarts, Kelly, Gutaker, Rafal M., Benz, Bruce, Blake, Michael, Bukowski, Robert, Holland, James, Kruse-Peeples, Melissa, Lepak, Nicholas, Prim, Lynda, Cinta Romay, M., Ross-Ibarra, Jeffrey, de Jesus Sanchez-Gonzalez, Jose, Schmidt, Chris, Schuenemann, Verena J., Krause, Johannes, Matson, R. G., Weigel, Detlef, Buckler, Edward S., and Burbano, Hernán A.
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GENOMICS , *CORN farming , *CORN reproduction , *ECOLOGICAL carrying capacity ,CORN analysis - Abstract
By 4000 years ago, people had introduced maize to the southwestern United States; full agriculture was established quickly in the lowland deserts but delayed in the temperate highlands for 2000 years. We test if the earliest uplandmaize was adapted for early flowering, a characteristic of modern temperate maize. We sequenced fifteen 1900-year-old maize cobs from Turkey Pen Shelter in the temperate Southwest. Indirectly validated genomic models predicted that Turkey Pen maize was marginally adapted with respect to flowering, as well as short, tillering, and segregating for yellow kernel color. Temperate adaptation drove modern population differentiation and was selected in situ from ancient standing variation. Validated prediction of polygenic traits improves our understanding of ancient phenotypes and the dynamics of environmental adaptation. [ABSTRACT FROM AUTHOR]
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- 2017
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17. Exploration of peptides bound to MHC class I molecules in melanoma.
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Pritchard, Antonia L., Hastie, Marcus L., Neller, Michelle, Gorman, Jeffrey J., Schmidt, Chris W., and Hayward, Nicholas K.
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PEPTIDES , *MAJOR histocompatibility complex , *MELANOMA , *HIGH performance liquid chromatography , *MASS spectrometry , *EPITOPES , *T cells - Abstract
Advancements in high-resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13 829 peptides were identified; 83-87% of these were 8-11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; m RNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA-type binding prediction for 10 078 9/10 mer peptides assigned 88-95% to a patient-specific HLA subtype, revealing a disparity in strength of predicted binding. HLA-B*27-specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells. [ABSTRACT FROM AUTHOR]
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- 2015
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18. In Vitro Analysis of Breast Cancer Cell Line Tumourspheres and Primary Human Breast Epithelia Mammospheres Demonstrates Inter- and Intrasphere Heterogeneity.
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Smart, Chanel E., Morrison, Brian J., Saunus, Jodi M., Vargas, Ana Cristina, Keith, Patricia, Reid, Lynne, Wockner, Leesa, Amiri, Marjan Askarian, Sarkar, Debina, Simpson, Peter T., Clarke, Catherine, Schmidt, Chris W., Reynolds, Brent A., Lakhani, Sunil R., and Lopez, J. Alejandro
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BREAST cancer , *CANCER cells , *EPITHELIAL cells , *CELL culture , *DEVELOPMENTAL biology , *CELL differentiation , *MOLECULAR biology - Abstract
Mammosphere and breast tumoursphere culture have gained popularity as in vitro assays for propagating and analysing normal and cancer stem cells. Whether the spheres derived from different sources or parent cultures themselves are indeed single entities enriched in stem/progenitor cells compared to other culture formats has not been fully determined. We surveyed sphere-forming capacity across 26 breast cell lines, immunophenotyped spheres from six luminal- and basal-like lines by immunohistochemistry and flow cytometry and compared clonogenicity between sphere, adherent and matrigel culture formats using in vitro functional assays. Analyses revealed morphological and molecular intra- and inter-sphere heterogeneity, consistent with adherent parental cell line phenotypes. Flow cytometry showed sphere culture does not universally enrich for markers previously associated with stem cell phenotypes, although we found some cell-line specific changes between sphere and adherent formats. Sphere-forming efficiency was significantly lower than adherent or matrigel clonogenicity and constant over serial passage. Surprisingly, self-renewal capacity of sphere-derived cells was similar/lower than other culture formats. We observed significant correlation between long-term-proliferating-cell symmetric division rates in sphere and adherent cultures, suggesting functional overlap between the compartments sustaining them. Experiments with normal primary human mammary epithelia, including sorted luminal (MUC1+) and basal/myoepithelial (CD10+) cells revealed distinct luminal-like, basal-like and mesenchymal entities amongst primary mammospheres. Morphological and colony-forming-cell assay data suggested mammosphere culture may enrich for a luminal progenitor phenotype, or induce reversion/relaxation of the basal/mesenchymal in vitro selection occurring with adherent culture. Overall, cell line tumourspheres and primary mammospheres are not homogenous entities enriched for stem cells, suggesting a more cautious approach to interpreting data from these assays and careful consideration of its limitations. Sphere culture may represent an alternative 3-dimensional culture system which rather than universally ‘enriching’ for stem cells, has utility as one of a suite of functional assays that provide a read-out of progenitor activity. [ABSTRACT FROM AUTHOR]
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- 2013
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19. Proteomic Comparison of MCF-7 Tumoursphere and Monolayer Cultures.
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Morrison, Brian J., Hastie, Marcus L., Grewal, Yadveer S., Bruce, Zara C., Schmidt, Chris, Reynolds, Brent A., Gorman, Jeffrey J., and Lopez, J. Alejandro
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BREAST cancer treatment , *PROTEOMICS , *CHEMICAL biology , *PROTEINS , *PHENOTYPES - Abstract
Breast cancer is a heterogenous disease, composed of tumour cells with differing gene expressions and phenotypes. Very few antigens have been identified and a better understanding of tumour initiating-cells as targets for therapy is critically needed. Recently, a rare subpopulation of cells within tumours has been described with the ability to: (i) initiate and sustain tumour growth; (ii) resist traditional therapies and allow for secondary tumour dissemination; and (iii) display some of the characteristics of stem cells such as self-renewal. These cells are termed tumour-initiating cells or cancer stem cells, or alternatively, in the case of breast cancer, breast cancer stem cells. Previous studies have demonstrated that breast cancer stem cells can be enriched for in ''tumoursphere'' culture. Proteomics represents a novel way to investigate protein expression between cells. We hypothesise that characterisation of the proteome of the breast cancer line MCF-7 tumourspheres compared to adherent/differentiated cells identifies proteins of novel interest for further isolating or targeting breast cancer stem cells. We present evidence that: (i) the proteome of adherent cells is different to the proteome of cells grown in sphere medium from either early passage (passage 2) or late passage (passage 5) spheres; (ii) that spheres are enriched in expression of a variety of tumour-relevant proteins (including MUC1 and Galectin-3); and (iii) that targeting of one of these identified proteins (galectin-3) using an inhibitor (N-acetyllactosamine) decreases sphere formation/selfrenewal of MCF-7 cancer stem cells in vitro and tumourigenicity in vivo. Hence, proteomic analysis of tumourspheres may find use in identifying novel targets for future therapy. The therapeutic targeting of breast cancer stem cells, a highly clinically relevant sub-population of tumour cells, has the potential to eliminate residual disease and may become an important component of a multi-modality treatment of cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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20. Fulminant Infectious Mononucleosis and Recurrent Epstein-Barr Virus Reactivation in an Adolescent.
- Author
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Nourse, Jamie P., Jones, Kimberley, Dua, Ujjwal, Runnegar, Naomi, Looke, David, Schmidt, Chris, Siok-Keen Tey, Kennedy, Glen, and Gandhi, Maher K.
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MONONUCLEOSIS , *EPSTEIN-Barr virus , *T cell receptors , *IMMUNITY , *INTERLEUKIN-2 , *GRAFT versus host disease , *STEM cell transplantation , *PHENOTYPES , *EPSTEIN-Barr virus diseases , *PATIENTS - Abstract
We describe a unique case of fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation presenting in an adolescent. Detailed assays of Epstein-Barr virus-specific T cell immunity revealed defects in the patient's T cell receptor signalling pathway characterized by a lack of interleukin-2 and CD25 expression, which may have contributed to her clinical course. Allogeneic stem cell transplantation reversed the clinical and laboratory phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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21. Immunostimulatory cancer chemotherapy using local ingenol-3-angelate and synergy with immunotherapies
- Author
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Le, Thuy T.T., Gardner, Joy, Hoang-Le, Diem, Schmidt, Chris W., MacDonald, Kelli P., Lambley, Eleanore, Schroder, Wayne A., Ogbourne, Steven M., and Suhrbier, Andreas
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IMMUNOLOGICAL adjuvants , *CANCER chemotherapy , *CANCER vaccines , *IMMUNOTHERAPY , *METASTASIS , *DRUG synergism , *GENE expression , *DENDRITIC cells , *PREVENTION - Abstract
Abstract: Ingenol-3-angelate is a new local chemotherapeutic agent in clinical trails that induces primary necrosis of tumour cells and transient local inflammation. Here we show that cure of subcutaneous tumours with ingenol-3-angelate (PEP005) resulted in the generation of anti-cancer CD8 T cells that could regress metastases. Furthermore, PEP005-mediated cure synergized with several CD8 T cell-based immunotherapies to regress further distant metastases. PEP005 was shown to have adjuvant properties, being able to upregulate CD80 and CD86 expression on dendritic cells in vivo, and to promote CD8 T cell induction when co-delivered with a protein antigen. PEP005 thus emerges as a unique local chemotherapeutic immunostimulatory debulking agent that could be used in conjunction with immunotherapies to promote regression of metastases. [Copyright &y& Elsevier]
- Published
- 2009
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22. A Population of HLA-DR+ Immature Cells Accumulates in the Blood Dendritic Cell Compartment of Patients with Different Types of Cancer.
- Author
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Pinzon-Charry, Alberto, Ho, Christopher S. K., Laherty, Richard, Maxwell, Tammy, Walker, David, Gardiner, Robert A., O'Connor, Linda, Pyke, Christopher, Schmidt, Chris, Furnival, Colin, and López, Jose Alejandro
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DENDRITIC cells , *IMMUNOSUPPRESSION , *CANCER , *TUMORS , *BREAST cancer - Abstract
Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c- CD123- immature cells that expressed high levels of HLA-DR+ immature cells (DR+IC). Although DR+IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR+IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-γ secretion by T-lymphocytes. Importantly, increased numbers of DR+IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR+IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR+IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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23. HLA-DR+ Immature Cells Exhibit Reduced Antigen-Presenting Cell Function But Respond to CD40 Stimulation.
- Author
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Pinzon-Charry, Alberto, Maxwell, Tammy, Prato, Sandro, Furnival, Colin, Schmidt, Chris, and López, José Alejandro
- Subjects
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DENDRITIC cells , *CANCER , *T cells , *IMMUNE response , *ANTIGENS - Abstract
Dendritic cells (DC) have been implicated in the defective function of the immune system during cancer progression. We have demonstrated that patients with cancer have fewer myeloid (CD11c+) and plasmacytoid (CD123hi) DC and a concurrent accumulation of CD11c-CD123- immature cells expressing HLA-DR (DR+IC). Notably, DR+IC from cancer patients have a reduced capacity to stimulate allogeneic T-cells. DR+IC are also present in healthy donors, albeit in smaller numbers. In this study, we assessed whether DR+IC could have an impact on the immune response by comparing their function with DC counterparts. For this purpose, DR+IC and DC were purified and tested in the presentation of antigens through major histocompatibility complex (MHC) II and MHC-I molecules. DR+IC were less efficient than DC at presenting antigens to T-cells. DR+IC induced a limited activation of T-cells, eliciting poor T-helper (Th) 1 and preferentially inducing Th2-biased responses. Importantly, despite DR+IC's poor responsiveness to inflammatory factors, in samples from healthy volunteers and breast cancer patients, CD40 ligation induced phenotypic maturation and interleukin 12 secretion, in turn generating more efficient T-cell responses. These data underscore the importance of inefficient antigen presentation as a mechanism for tumor evasion and suggest an approach to improve the efficacy of DC-based immunotherapy for cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
24. Fire Detection Using GOES Rapid Scan Imagery.
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Weaver, John F., Lindsey, Dan, Bikos, Dan, Schmidt, Chris C., and Prins, Elaine
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WILDFIRES , *FOREST fires , *GEOPHYSICAL prediction , *GEOSTATIONARY satellites , *FUTURES studies , *CLIMATOLOGY , *METEOROLOGICAL research , *EARTH sciences - Abstract
This paper demonstrates the proper use of geostationary satellite imagery in wildland fire detection. The roles of both the visible and the 3.9- m channels are emphasized. Case studies from June 2002 are presented to illustrate techniques that can be utilized in both the detection and short-range forecasting processes. The examples demonstrate that, when utilized correctly, the sensitivity of the shortwave infrared channel to subpixel heat sources can often result in detections that match the timelines of human observations. Finally, a derived satellite product that increases the detection rate of wildland fires from space is described. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
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25. Microarray expression profiling in melanoma reveals a BRAF mutation signature.
- Author
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Pavey, Sandra, Johansson, Peter, Packer, Leisl, Taylor, Jennifer, Stark, Mitchell, Pollock, Pamela M., Walker, Graeme J., Boyle, Glen M., Harper, Ursula, Cozzi, Sarah-Jane, Hansen, Katherine, Yudt, Laura, Schmidt, Chris, Hersey, Peter, Ellem, Kay A. O., O'Rourke, Michael G. E., Parsons, Peter G., Meltzer, Paul, Ringnér, Markus, and Hayward, Nicholas K.
- Subjects
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GENE expression , *CELL lines , *MELANOMA , *MULTIDIMENSIONAL scaling , *PROTEIN kinases , *DNA microarrays - Abstract
We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
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