27 results on '"Torrence ME"'
Search Results
2. Development of a targeted amplicon sequencing method for genotyping Cyclospora cayetanensis from fresh produce and clinical samples with enhanced genomic resolution and sensitivity.
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Leonard SR, Mammel MK, Gharizadeh B, Almeria S, Ma Z, Lipman DJ, Torrence ME, Wang C, and Musser SM
- Abstract
Outbreaks of cyclosporiasis, an enteric illness caused by the parasite Cyclospora cayetanensis , have been associated with consumption of various types of fresh produce. Although a method is in use for genotyping C. cayetanensis from clinical specimens, the very low abundance of C. cayetanensis in food and environmental samples presents a greater challenge. To complement epidemiological investigations, a molecular surveillance tool is needed for use in genetic linkage of food vehicles to cyclosporiasis illnesses, estimation of the scope of outbreaks or clusters of illness, and determination of geographical areas involved. We developed a targeted amplicon sequencing (TAS) assay that incorporates a further enrichment step to gain the requisite sensitivity for genotyping C. cayetanensis contaminating fresh produce samples. The TAS assay targets 52 loci, 49 of which are located in the nuclear genome, and encompasses 396 currently known SNP sites. The performance of the TAS assay was evaluated using lettuce, basil, cilantro, salad mix, and blackberries inoculated with C. cayetanensis oocysts. A minimum of 24 markers were haplotyped even at low contamination levels of 10 oocysts in 25 g leafy greens. The artificially contaminated fresh produce samples were included in a genetic distance analysis based on haplotype presence/absence with publicly available C. cayetanensis whole genome sequence assemblies. Oocysts from two different sources were used for inoculation, and samples receiving the same oocyst preparation clustered together, but separately from the other group, demonstrating the utility of the assay for genetically linking samples. Clinical fecal samples with low parasite loads were also successfully genotyped. This work represents a significant advance in the ability to genotype C. cayetanensis contaminating fresh produce along with greatly expanding the genomic diversity included for genetic clustering of clinical specimens., Competing Interests: CW, BG, and ZM were employed by Chapter Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leonard, Mammel, Gharizadeh, Almeria, Ma, Lipman, Torrence, Wang and Musser.)
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- 2023
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3. mTORC1 regulates a lysosome-dependent adaptive shift in intracellular lipid species.
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Hosios AM, Wilkinson ME, McNamara MC, Kalafut KC, Torrence ME, Asara JM, and Manning BD
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- Mice, Animals, Mechanistic Target of Rapamycin Complex 1 metabolism, Triglycerides metabolism, Phospholipids metabolism, Lysosomes metabolism, Fatty Acids metabolism
- Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) senses and relays environmental signals from growth factors and nutrients to metabolic networks and adaptive cellular systems to control the synthesis and breakdown of macromolecules; however, beyond inducing de novo lipid synthesis, the role of mTORC1 in controlling cellular lipid content remains poorly understood. Here we show that inhibition of mTORC1 via small molecule inhibitors or nutrient deprivation leads to the accumulation of intracellular triglycerides in both cultured cells and a mouse tumor model. The elevated triglyceride pool following mTORC1 inhibition stems from the lysosome-dependent, but autophagy-independent, hydrolysis of phospholipid fatty acids. The liberated fatty acids are available for either triglyceride synthesis or β-oxidation. Distinct from the established role of mTORC1 activation in promoting de novo lipid synthesis, our data indicate that mTORC1 inhibition triggers membrane phospholipid trafficking to the lysosome for catabolism and an adaptive shift in the use of constituent fatty acids for storage or energy production., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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4. Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex.
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McNamara MC, Hosios AM, Torrence ME, Zhao T, Fraser C, Wilkinson M, Kwiatkowski DJ, Henske EP, Wu CL, Sarosiek KA, Valvezan AJ, and Manning BD
- Abstract
mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis. In TSC2-deficient cells and tumors, we find that mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2 and BCL-X
L for survival, thereby altering susceptibility to BH3 mimetics that target specific pro-survival BCL-2 proteins. The BCL-2/BCL-XL inhibitor ABT-263 synergizes with rapamycin to induce apoptosis in TSC-deficient cells and in a mouse tumor model of TSC, resulting in a more complete and durable response. These data expose a therapeutic vulnerability in regulation of the apoptotic machinery downstream of mTORC1 that promotes a cytotoxic response to rapamycin., Competing Interests: B.D.M. is a member of the scientific advisory board and a shareholder of Navitor Pharmaceuticals. D.J.K. reports receiving grants from Genentech, Revolution Medicines, and AADI and consulting fees from AADI, Guidepoint, and BridgeBio Gene Therapy., (© 2022 The Author(s).)- Published
- 2022
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5. The non-essential TSC complex component TBC1D7 restricts tissue mTORC1 signaling and brain and neuron growth.
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Schrötter S, Yuskaitis CJ, MacArthur MR, Mitchell SJ, Hosios AM, Osipovich M, Torrence ME, Mitchell JR, Hoxhaj G, Sahin M, and Manning BD
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- Animals, Mice, Mice, Knockout, Tuberous Sclerosis Complex 2 Protein metabolism, Brain growth & development, Brain metabolism, Intracellular Signaling Peptides and Proteins metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Neurons cytology, Neurons metabolism, Tuberous Sclerosis metabolism, Tuberous Sclerosis pathology, Tuberous Sclerosis Complex 1 Protein metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism
- Abstract
The tuberous sclerosis complex (TSC) 1 and 2 proteins associate with TBC1D7 to form the TSC complex, which is an essential suppressor of mTOR complex 1 (mTORC1), a ubiquitous driver of cell and tissue growth. Loss-of-function mutations in TSC1 or TSC2, but not TBC1D7, give rise to TSC, a pleiotropic disorder with aberrant activation of mTORC1 in various tissues. Here, we characterize mice with genetic deletion of Tbc1d7, which are viable with normal growth and development. Consistent with partial loss of function of the TSC complex, Tbc1d7 knockout (KO) mice display variable increases in tissue mTORC1 signaling with increased muscle fiber size but with strength and motor defects. Their most pronounced phenotype is brain overgrowth due to thickening of the cerebral cortex, with enhanced neuron-intrinsic mTORC1 signaling and growth. Thus, TBC1D7 is required for full TSC complex function in tissues, and the brain is particularly sensitive to its growth-suppressing activities., Competing Interests: Declaration of interests B.D.M. is a member of the scientific advisory board and a shareholder of Navitor Pharmaceuticals. M.S. reports grant support from Novartis, Biogen, Astellas, Aeovian, Bridgebio, and Aucta and is on the scientific advisory boards for Novartis, Roche, Regenxbio, SpringWorks Therapeutics, Jaguar Therapeutics, and Alkermes. All other authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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6. The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals.
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Torrence ME, MacArthur MR, Hosios AM, Valvezan AJ, Asara JM, Mitchell JR, and Manning BD
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- Activating Transcription Factor 4 genetics, Animals, Cell Line, Cell Line, Tumor, Embryo, Mammalian, Fibroblasts, Humans, Insulin pharmacology, Mechanistic Target of Rapamycin Complex 1 genetics, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Signal Transduction, Activating Transcription Factor 4 metabolism, Glutathione biosynthesis, Mechanistic Target of Rapamycin Complex 1 drug effects
- Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) stimulates a coordinated anabolic program in response to growth-promoting signals. Paradoxically, recent studies indicate that mTORC1 can activate the transcription factor ATF4 through mechanisms distinct from its canonical induction by the integrated stress response (ISR). However, its broader roles as a downstream target of mTORC1 are unknown. Therefore, we directly compared ATF4-dependent transcriptional changes induced upon insulin-stimulated mTORC1 signaling to those activated by the ISR. In multiple mouse embryo fibroblast and human cancer cell lines, the mTORC1-ATF4 pathway stimulated expression of only a subset of the ATF4 target genes induced by the ISR, including genes involved in amino acid uptake, synthesis, and tRNA charging. We demonstrate that ATF4 is a metabolic effector of mTORC1 involved in both its established role in promoting protein synthesis and in a previously unappreciated function for mTORC1 in stimulating cellular cystine uptake and glutathione synthesis., Competing Interests: MT, MM, AH, AV, JA, JM No competing interests declared, BM Brendan Manning is a scientific advisory board member and stockholder of Navitor Pharmaceuticals and LAM Therapeutics., (© 2021, Torrence et al.)
- Published
- 2021
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7. A scoping review of the detection, epidemiology and control of Cyclospora cayetanensis with an emphasis on produce, water and soil.
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Totton SC, O'Connor AM, Naganathan T, Martinez BAF, Vriezen ER, Torrence ME, and Sargeant JM
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- Cyclospora isolation & purification, Food Parasitology, Fruit parasitology, Soil parasitology, Vegetables parasitology, Water parasitology
- Abstract
Cyclospora cayetanensis is a parasite causing cyclosporiasis (an illness in humans). Produce (fruits, vegetables, herbs), water and soil contaminated with C. cayetanensis have been implicated in human infection. The objective was to conduct a scoping review of primary research in English on the detection, epidemiology and control of C. cayetanensis with an emphasis on produce, water and soil. MEDLINE® (Web of ScienceTM), Agricola (ProQuest), CABI Global Health, and Food Science and Technology Abstracts (EBSCOhost) were searched from 1979 to February 2020. Of the 349 relevant primary research studies identified, there were 75 detection-method studies, 40 molecular characterisation studies, 38 studies of Cyclospora in the environment (33 prevalence studies, 10 studies of factors associated with environmental contamination), 246 human infection studies (212 prevalence/incidence studies, 32 outbreak studies, 60 studies of environmental factors associated with non-outbreak human infection) and eight control studies. There appears to be sufficient literature for a systematic review of prevalence and factors associated with human infection with C. cayetanensis. There is a dearth of publicly available detection-method studies in soil (n = 0) and water (n = 2), prevalence studies on soil (n = 1) and studies of the control of Cyclospora (particularly on produce prior to retail (n = 0)).
- Published
- 2021
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8. IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex.
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Valvezan AJ, McNamara MC, Miller SK, Torrence ME, Asara JM, Henske EP, and Manning BD
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- Animals, Cell Line, IMP Dehydrogenase genetics, IMP Dehydrogenase metabolism, Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors, Mechanistic Target of Rapamycin Complex 1 genetics, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Mice, Knockout, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Tuberous Sclerosis genetics, Tuberous Sclerosis metabolism, Tuberous Sclerosis pathology, Enzyme Inhibitors pharmacology, IMP Dehydrogenase antagonists & inhibitors, Mycophenolic Acid pharmacology, Neoplasm Proteins antagonists & inhibitors, Ribonucleosides pharmacology, Tuberous Sclerosis drug therapy
- Abstract
Recent studies in distinct preclinical tumor models have established the nucleotide synthesis enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) as a viable target for antitumor therapy. IMPDH inhibitors have been used clinically for decades as safe and effective immunosuppressants. However, the potential to repurpose these pharmacological agents for antitumor therapy requires further investigation, including direct comparisons of available compounds. Therefore, we tested structurally distinct IMPDH inhibitors in multiple cell and mouse tumor models of the genetic tumor syndrome tuberous sclerosis complex (TSC). TSC-associated tumors are driven by uncontrolled activation of the growth-promoting protein kinase complex mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), which is also aberrantly activated in the majority of sporadic cancers. Despite eliciting similar immunosuppressive effects, the IMPDH inhibitor mizoribine, used clinically throughout Asia, demonstrated far superior antitumor activity compared with the FDA-approved IMPDH inhibitor mycophenolate mofetil (or CellCept, a prodrug of mycophenolic acid). When compared directly to the mTOR inhibitor rapamycin, mizoribine treatment provided a more durable antitumor response associated with tumor cell death. These results provide preclinical support for repurposing mizoribine, over other IMPDH inhibitors, as an alternative to mTOR inhibitors for the treatment of TSC-associated tumors and possibly other tumors featuring uncontrolled mTORC1 activity.
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- 2020
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9. Editorial.
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Torrence ME
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- Animals, Humans, Periodicals as Topic, Public Health trends, Zoonoses transmission
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- 2019
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10. Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions.
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Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T, Borge L, Lac S, Roques J, Lavaut MN, Berthezène P, Rubis M, Secq V, Garcia S, Moutardier V, Lombardo D, Iovanna JL, Tomasini R, Guillaumond F, Vander Heiden MG, and Vasseur S
- Subjects
- Animals, Biological Transport, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Cell Line, Tumor, Cell Proliferation, Cell Survival, Collagen chemistry, Extracellular Matrix chemistry, Extracellular Matrix metabolism, Humans, Male, Matrix Metalloproteinase 13 genetics, Matrix Metalloproteinase 13 metabolism, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Transgenic, Neoplasm Transplantation, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Procollagen-Proline Dioxygenase genetics, Procollagen-Proline Dioxygenase metabolism, Proline Oxidase metabolism, Signal Transduction, Carcinoma, Pancreatic Ductal genetics, Collagen metabolism, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms genetics, Proline metabolism, Proline Oxidase genetics
- Abstract
Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.
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- 2017
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11. Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology-Veterinary (STROBE-Vet) Statement.
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Sargeant JM, O'Connor AM, Dohoo IR, Erb HN, Cevallos M, Egger M, Ersbøll AK, Martin SW, Nielsen LR, Pearl DL, Pfeiffer DU, Sanchez J, Torrence ME, Vigre H, Waldner C, and Ward MP
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- Animals, Aquaculture, Canada, Food Safety, Publishing, Observation, Surveys and Questionnaires
- Abstract
Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. Our objective was to develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. We conducted a consensus meeting with 17 experts in Mississauga, Canada. Experts completed a premeeting survey about whether items in the STROBE statement should be modified or added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. During the meeting, each STROBE item was discussed to determine whether or not rewording was recommended, and whether additions were warranted. Anonymous voting was used to determine consensus. Six items required no modifications or additions. Modifications or additions were made to the STROBE items 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources and measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). The methods and processes used were similar to those used for other extensions of the STROBE statement. The use of this STROBE statement extension should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.
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- 2016
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12. Explanation and Elaboration Document for the STROBE-Vet Statement: Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary Extension.
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O'Connor AM, Sargeant JM, Dohoo IR, Erb HN, Cevallos M, Egger M, Ersbøll AK, Martin SW, Nielsen LR, Pearl DL, Pfeiffer DU, Sanchez J, Torrence ME, Vigre H, Waldner C, and Ward MP
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- Animal Husbandry standards, Animals, Animals, Domestic, Veterinary Medicine methods, Veterinary Medicine standards, Epidemiology standards, Observational Studies as Topic standards, Research standards
- Abstract
The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement was first published in 2007 and again in 2014. The purpose of the original STROBE was to provide guidance for authors, reviewers and editors to improve the comprehensiveness of reporting; however, STROBE has a unique focus on observational studies. Although much of the guidance provided by the original STROBE document is directly applicable, it was deemed useful to map those statements to veterinary concepts, provide veterinary examples and highlight unique aspects of reporting in veterinary observational studies. Here, we present the examples and explanations for the checklist items included in the STROBE-Vet Statement. Thus, this is a companion document to the STROBE-Vet Statement Methods and process document, which describes the checklist and how it was developed., (© 2016 The Authors. Zoonoses and Public Health published by Blackwell Verlag GmbH.)
- Published
- 2016
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13. Introduction to Preharvest Food Safety.
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Torrence ME
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- Agriculture standards, Animal Husbandry standards, Animals, Cattle, Consumer Product Safety standards, Food Microbiology methods, Food Microbiology standards, Foodborne Diseases epidemiology, Foodborne Diseases microbiology, Poultry, Public Health, Agriculture methods, Animal Husbandry methods, Food Contamination prevention & control, Food Safety methods, Foodborne Diseases prevention & control
- Abstract
This introductory article provides an overview of preharvest food safety activities and initiatives for the past 15 years. The section on traditional areas of preharvest food safety focuses on significant scientific advancements that are a culmination of collaborative efforts (both public health and agriculture) and significant research results. The highlighted advancements provide the foundation for exploring future preharvest areas and for improving and focusing on more specific intervention/control/prevention strategies. Examples include Escherichia coli and cattle, Salmonella and Campylobacter in poultry, and interventions and prevention and control programs. The section on "nontraditional" preharvest food safety areas brings attention to potential emerging food safety issues and to future food safety research directions. These include organic production, the FDA's Produce Rule (water and manure), genomic sequencing, antimicrobial resistance, and performance metrics. The concluding section emphasizes important themes such as strategic planning, coordination, epidemiology, and the need for understanding food safety production as a continuum. Food safety research, whether at the pre- or postharvest level, will continue to be a fascinating complex web of foodborne pathogens, risk factors, and scientific and policy interactions. Food safety priorities and research must continue to evolve with emerging global issues, emerging technologies, and methods but remain grounded in a multidisciplinary, collaborative, and systematic approach.
- Published
- 2016
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14. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers.
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Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM, Bauer MR, Lau AN, Ji BW, Dixit PD, Hosios AM, Muir A, Chin CR, Freinkman E, Jacks T, Wolpin BM, Vitkup D, and Vander Heiden MG
- Subjects
- Animals, Gene Expression Regulation, Neoplastic, Humans, Male, Metabolic Networks and Pathways, Mice, Mice, Inbred C57BL, Minor Histocompatibility Antigens genetics, Mutation, Nitrogen metabolism, Organ Specificity, Pregnancy Proteins genetics, Transaminases genetics, Amino Acids, Branched-Chain metabolism, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal metabolism, Lung Neoplasms genetics, Lung Neoplasms metabolism, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements., (Copyright © 2016, American Association for the Advancement of Science.)
- Published
- 2016
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15. Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.
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Yuan C, Clish CB, Wu C, Mayers JR, Kraft P, Townsend MK, Zhang M, Tworoger SS, Bao Y, Qian ZR, Rubinson DA, Ng K, Giovannucci EL, Ogino S, Stampfer MJ, Gaziano JM, Ma J, Sesso HD, Anderson GL, Cochrane BB, Manson JE, Torrence ME, Kimmelman AC, Amundadottir LT, Vander Heiden MG, Fuchs CS, and Wolpin BM
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- Aconitic Acid blood, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Genotype, Humans, Isocitrates blood, Kaplan-Meier Estimate, Male, Middle Aged, Nurses, Odds Ratio, Pancreatic Neoplasms diagnosis, Proportional Hazards Models, Prospective Studies, United States epidemiology, Women's Health, Biomarkers, Tumor blood, Iron Regulatory Protein 1 blood, Iron Regulatory Protein 1 genetics, Pancreatic Neoplasms blood, Pancreatic Neoplasms mortality, Polymorphism, Single Nucleotide, Tricarboxylic Acids blood
- Abstract
Background: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown., Methods: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided., Results: Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate., Conclusions: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
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16. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development.
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Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, Yuan C, Bao Y, Townsend MK, Tworoger SS, Davidson SM, Papagiannakopoulos T, Yang A, Dayton TL, Ogino S, Stampfer MJ, Giovannucci EL, Qian ZR, Rubinson DA, Ma J, Sesso HD, Gaziano JM, Cochrane BB, Liu S, Wactawski-Wende J, Manson JE, Pollak MN, Kimmelman AC, Souza A, Pierce K, Wang TJ, Gerszten RE, Fuchs CS, Vander Heiden MG, and Wolpin BM
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Carcinoma, Pancreatic Ductal etiology, Case-Control Studies, Cohort Studies, Disease Models, Animal, Disease Progression, Female, Humans, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Pancreatic Neoplasms etiology, Prospective Studies, Proto-Oncogene Proteins p21(ras) genetics, Risk Factors, Time Factors, Amino Acids, Branched-Chain blood, Carcinoma, Pancreatic Ductal blood, Pancreatic Neoplasms blood
- Abstract
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.
- Published
- 2014
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17. The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety by modifying the CONSORT statement.
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O'Connor AM, Sargeant JM, Gardner IA, Dickson JS, Torrence ME, Dewey CE, Dohoo IR, Evans RB, Gray JT, Greiner M, Keefe G, Lefebvre SL, Morley PS, Ramirez A, Sischo W, Smith DR, Snedeker K, Sofos J, Ward MP, and Wills R
- Subjects
- Animal Welfare, Animals, Animals, Domestic, Consumer Product Safety, Editorial Policies, Humans, Periodicals as Topic standards, Publishing standards, Writing standards, Guidelines as Topic, Randomized Controlled Trials as Topic standards
- Abstract
The conduct of randomized controlled trials in livestock with production, health and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on 18-19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food-safety outcomes.
- Published
- 2010
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18. The REFLECT statement: reporting guidelines for randomized controlled trials in livestock and food safety: explanation and elaboration.
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Sargeant JM, O'Connor AM, Gardner IA, Dickson JS, Torrence ME, Dohoo IR, Lefebvre SL, Morley PS, Ramirez A, and Snedeker K
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- Animal Welfare, Animals, Animals, Domestic, Consumer Product Safety, Editorial Policies, Humans, Periodicals as Topic standards, Publishing standards, Writing standards, Guidelines as Topic, Randomized Controlled Trials as Topic standards
- Abstract
Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision-making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996 with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies, the use of a deliberate challenge model in some trials, and common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.
- Published
- 2010
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19. The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.
- Author
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O'Connor AM, Sargeant JM, Gardner IA, Dickson JS, Torrence ME, Dewey CE, Dohoo IR, Evans RB, Gray JT, Greiner M, Keefe G, Lefebvre SL, Morley PS, Ramirez A, Sischo W, Smith DR, Snedeker K, Sofos JN, Ward MP, and Wills R
- Subjects
- Animal Welfare, Animals, Animals, Domestic, Consumer Product Safety, Editorial Policies, Humans, Periodicals as Topic standards, Publishing standards, Writing standards, Guidelines as Topic, Randomized Controlled Trials as Topic standards
- Abstract
The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, Ill, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.
- Published
- 2010
- Full Text
- View/download PDF
20. ASAS Centennial Paper: Developments and future outlook for preharvest food safety.
- Author
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Oliver SP, Patel DA, Callaway TR, and Torrence ME
- Subjects
- Animals, Food Microbiology, Public Health, Agriculture standards, Agriculture trends, Consumer Product Safety, Food Contamination prevention & control
- Abstract
The last century of food animal agriculture is a remarkable triumph of scientific research. Knowledge derived through research has resulted in the development and use of new technologies that have increased the efficiency of food production and created a huge animal production and food manufacturing industry capable of feeding the US population while also providing significant quantities of high-quality food for export to other countries. Although the US food supply is among the safest in the world, the US Center for Disease Prevention and Control estimates that 76 million people get sick, more than 300,000 are hospitalized, and 5,000 die each year from foodborne illness. Consequently, preventing foodborne illness and death remains a major public health concern. Challenges to providing a safe, abundant, and nutritious food supply are complex because all aspects of food production, from farm to fork, must be considered. Given the national and international demand and expectations for food safety as well as the formidable challenges of producing and maintaining a safe food supply, food safety research and educational programs have taken on a new urgency. Remarkable progress has been made during the last century. Wisdom from a century of animal agriculture research now includes the realization that on-farm pathogens are intricately associated with animal health and well-being, the production of high-quality food, and profitability. In this review, some of the developments that have occurred over the last few decades are summarized, including types, sources, and concentrations of disease-causing pathogens encountered in food-producing animal environments and their association with food safety; current and future methods to control or reduce foodborne pathogens on the farm; and present and future preharvest food safety research directions. Future scientific breakthroughs will no doubt have a profound impact on animal agriculture and the production of high-quality food, but we will also be faced with moral, ethical, and societal dilemmas that must be reconciled. A strong, science-based approach that addresses all the complex issues involved in continuing to improve food safety and public health is necessary to prevent foodborne illnesses. Not only must research be conducted to solve complex food safety issues, but results of that research must also be communicated effectively to producers and consumers.
- Published
- 2009
- Full Text
- View/download PDF
21. Methodological quality assessment of review articles evaluating interventions to improve microbial food safety.
- Author
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Sargeant JM, Torrence ME, Rajić A, O'Connor AM, and Williams J
- Subjects
- Animals, Humans, Risk Assessment, Consumer Product Safety, Food Contamination analysis, Meta-Analysis as Topic, Review Literature as Topic
- Abstract
Review articles are a means of summarizing the potentially vast volume of research on a topic. However, the methodological quality of review articles varies, and reviews on the same topic may reach different conclusions. We evaluated 65 review articles published between 2000 and 2005 that addressed the effectiveness of microbial food safety interventions, using criteria for methodological soundness developed in the medical field. Overall, the methodological quality of the review articles was poor, with none of the reviews providing information on the method of locating primary research studies or the inclusion/exclusion criteria for selecting primary studies. None of the reviews included a critical appraisal of the methodological quality of the primary studies. Less than half of the reviews stated a focused research question, explored possible reasons for differences in the results of primary studies, discussed the generalizability of results, or proposed directions for future research. There is a need to improve the methodological quality of review articles on microbial food safety interventions if they are to be of use in policy and decision making.
- Published
- 2006
- Full Text
- View/download PDF
22. Epidemiology and food safety.
- Author
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Torrence ME
- Subjects
- Epidemiologic Studies, Forecasting, Humans, Research, United States, United States Department of Agriculture, United States Dept. of Health and Human Services, Consumer Product Safety standards, Population Surveillance, Public Health
- Abstract
With the introduction of the Food Safety Initiative in 1997, food safety activities and research funding have increased dramatically. Advances in microbiological methods and epidemiologic research have provided significant progress in our understanding of foodborne diseases and in our implementation of control programs. This article highlights some of those food safety activities and epidemiologic research programs. This article also describes potential future research areas and activities.
- Published
- 2005
- Full Text
- View/download PDF
23. Data sources: use in the epidemiologic study of medical devices.
- Author
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Torrence ME
- Subjects
- Centers for Disease Control and Prevention, U.S., Humans, Medicare, Product Surveillance, Postmarketing, United States, United States Food and Drug Administration, Data Collection methods, Epidemiologic Methods, Equipment and Supplies
- Abstract
Medical device epidemiology is the study of the prevalence and incidence of use, effectiveness, and adverse events associated with medical devices in a population. The identification of large data sources with medical device data provides a large population for epidemiologic studies. Two challenges in medical device epidemiology are the ability to find data on the specific device and the exposure of a patient to that device. This paper identifies data sources both from the govenment and from the private sector that can be used for epidemiologic studies of medical devices and, to a limited degree, studies of medical devices in women. Each source provides data for different types of devices and in differing specificity. The paper also discusses briefly the strengths and weaknesses of each data source. More data sources are needed to enhance the study of medical device epidemiology. Additional efforts and focus are needed to enhance the ability to study medical devices in women.
- Published
- 2002
- Full Text
- View/download PDF
24. The Role of Antibiotics in Agriculture: This report is based on a colloquium sponsored by the American Academy of Microbiology held November 2–4, 2001, in Santa Fe, New Mexico.
- Author
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Isaacson RE and Torrence ME
- Abstract
The development of antibiotics has provided much success against infectious diseases in animals and humans. But the intensive and extensive use of antibiotics over the years has resulted in the emergence of drug-resistant bacterial pathogens. The existence of a reservoir(s) of antibiotic resistant bacteria and antibiotic resistance genes in an interactive environment of animals, plants, and humans provides the opportunity for further transfer and dissemination of antibiotic resistance. The emergence of antibiotic resistant bacteria has created growing concern about its impact on animal and human health. To specifically address the impact of antibiotic resistance resulting from the use of antibiotics in agriculture, the American Academy of Microbiology convened a colloquium, “Antibiotic Resistance and the Role of Antimicrobials in Agriculture: A Critical Scientific Assessment,” in Santa Fe, New Mexico, November 2–4, 2001. Colloquium participants included academic, industrial, and government researchers with a wide range of expertise, including veterinary medicine, microbiology, food science, pharmacology, and ecology. These scientists were asked to provide their expert opinions on the current status of antibiotic usage and antibiotic resistance, current research information, and provide recommendations for future research needs. The research areas to be addressed were roughly categorized under the following areas: ▪ Origins and reservoirs of resistance; ▪ Transfer of resistance; ▪ Overcoming/modulating resistance by altering usage; and ▪ Interrupting transfer of resistance. The consensus of colloquium participants was that the evaluation of antibiotic usage and its impact were complex and subject to much speculation and polarization. Part of the complexity stems from the diverse array of animals and production practices for food animal production. The overwhelming consensus was that any use of antibiotics creates the possibility for the development of antibiotic resistance, and that there already exist pools of antibiotic resistance genes and antibiotic resistant bacteria. Much discussion revolved around the measurement of antibiotic usage, the measurement of antibiotic resistance, and the ability to evaluate the impact of various types of usage (animal, human) on overall antibiotic resistance. Additionally, many participants identified commensal bacteria as having a possible role in the continuance of antibiotic resistance as reservoirs. Participants agreed that many of the research questions could not be answered completely because of their complexity and the need for better technologies. The concept of the “smoking gun” to indicate that a specific animal source was important in the emergence of certain antibiotic resistant pathogens was discussed, and it was agreed that ascribing ultimate responsibility is likely to be impossible. There was agreement that expanded and more improved surveillance would add to current knowledge. Science-based risk assessments would provide better direction in the future. As far as preventive or intervention activities, colloquium participants reiterated the need for judicious/prudent use guidelines. Yet they also emphasized the need for better dissemination and incorporation by end-users. It is essential that there are studies to measure the impact of educational efforts on antibiotic usage. Other recommendations included alternatives to antibiotics, such as commonly mentioned vaccines and probiotics. There also was an emphasis on management or production practices that might decrease the need for antibiotics. Participants also stressed the need to train new researchers and to interest students in postdoctoral work, through training grants, periodic workshops, and comprehensive conferences. This would provide the expertise needed to address these difficult issues in the future. Finally, the participants noted that scientific societies and professional organizations should play a pivotal role in providing technical advice, distilling and disseminating information to scientists, media, and consumers, and in increasing the visibility and funding for these important issues. The overall conclusion is that antibiotic resistance remains a complex issue with no simple answers. This reinforces the messages from other meetings. The recommendations from this colloquium provide some insightful directions for future research and action., (Copyright 2002 American Academy of Microbiology.)
- Published
- 2002
- Full Text
- View/download PDF
25. Activities to address antimicrobial resistance in the United States.
- Author
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Torrence ME
- Subjects
- Animals, Humans, United States epidemiology, Veterinary Drugs, Disease Notification methods, Drug Resistance, Microbial
- Abstract
Antimicrobials are essential for the prevention and treatment of bacterial infections in humans and animals. Subtherapeutic antimicrobials have been used as growth promoters for >40 years. The subject of antimicrobial resistance is not new but has gained increasing attention due to public-health concerns about multi-resistant pathogenic organisms. Numerous United States' activities do exist to address antimicrobial resistance. A surveillance system (the National Antimicrobial Resistance Monitoring System) was established in 1996 to monitor changes over time in resistance for 17 antibiotics in humans and animals. Educational campaigns have been created to promote the judicious therapeutic use of antimicrobials. Producer groups are developing guidelines for judicious therapeutic antimicrobial use for their prospective species. Basic and applied research programs are being expanded to answer many of the unsolved questions regarding development, persistence, and transmission of antimicrobial resistance. This paper focuses on a federal inter-agency public-health action plan to combat antimicrobial resistance; the plan was released for public comment in 2000. This plan addresses goals and actions to combat antimicrobial resistance in humans and agriculture in four areas: surveillance; research; prevention and control; product development.
- Published
- 2001
- Full Text
- View/download PDF
26. Preliminary survey of the occurrence of anaphylactoid reactions during haemodialysis.
- Author
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Bright RA, Torrence ME, Daley WR, and McClellan WM
- Subjects
- Adult, Aged, Angiotensin-Converting Enzyme Inhibitors adverse effects, Bradykinin physiology, Female, Humans, Male, Membranes, Artificial, Middle Aged, Anaphylaxis etiology, Renal Dialysis adverse effects
- Published
- 1999
- Full Text
- View/download PDF
27. Epidemiology of raccoon rabies in Virginia, 1984 to 1989.
- Author
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Torrence ME, Jenkins SR, and Glickman LT
- Subjects
- Animals, Rabies epidemiology, Seasons, Virginia epidemiology, Disease Outbreaks veterinary, Rabies veterinary, Raccoons
- Abstract
Geographical and temporal trends in reports of rabid raccoons (Procyon lotor) in Virginia were summarized for 1984 to 1989; 3,256 raccoons were submitted for rabies testing, of which 1,053 (32.3%) had rabies. Both the absolute number of rabid raccoons and the percent of rabid raccoons (number rabid divided by number submitted) were examined for seasonal and yearly trends. Geographically, the epidemic moved eastward and southward in the state. The seasonal trend showed bimodal peaks in late winter and early fall and a seasonal low in summer. The percent of rabies positive raccoons peaked 1 mo earlier than the absolute number of rabies positive raccoons. The peak in the number of rabies positive raccoons occurred in 1987, while the percent of rabies positive raccoons peaked in 1986. These trends were used to recommend timing and placement of oral vaccine as one strategy to control raccoon rabies in wildlife.
- Published
- 1992
- Full Text
- View/download PDF
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