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"Stevens, Brian"
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Aircraft control and simulation : dynamics, controls design, and autonomous systems
This third edition is a comprehensive guide to aircraft control and simulation. The updated text covers flight control systems, flight dynamics, aircraft modelling, and flight simulation from both classical design and modern perspectives, as well as two new chapters on the modelling, simulation, and adaptive control of unmanned aerial vehicles.
Book
Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021–2022
We present the results of Canada’s Interagency Surveillance Program for Avian Influenza in Wild Birds in the year following the first detection of highly pathogenic avian influenza virus (HPAIV) H5N1 on the continent. The surveillance program tested over 17,000 wild birds, both sick and apparently healthy, which revealed spatiotemporal and taxonomic patterns in HPAIV prevalence and mortality across Canada. The significant shift in the presence and distribution of HPAIV in Canada’s wild birds underscores the need for sustained investment in wild bird surveillance and collaboration across One Health partners.
Journal Article
Twenty years of ungulate disease surveillance by the Canadian Wildlife Health Cooperative (2003–2022)
Free-ranging wild ungulates are integral to the health and well-being of Canadian socioecological systems, contributing various One Health benefits (e.g., nutrient cycling, sustainable food resources) to the people and other animals that coexist with them. In North America, ungulates face a range of threats to their population health. To address knowledge gaps surrounding the health of Canadian ungulates, we conducted a retrospective analysis of 20 years of ungulate morbidity and mortality data collected through passive disease surveillance conducted by the Canadian Wildlife Health Cooperative (CWHC) and through submissions from collaborative partners. In total, 2525 cases across 12 species were assigned a category of diagnosis (COD) by a CWHC veterinary pathologist. Infectious/ inflammatory/ transmissible CODs accounted for 53.0% of all cases, with two diagnoses made most frequently: chronic wasting disease (CWD) and Parelaphostrongylus tenuis ( P. tenuis ) infection. We identified a significant increase in the proportion of cervid cases diagnosed with CWD in Saskatchewan that was consistent across species, with the odds of an individual cervid in Saskatchewan being CWD positive increasing by 22% per year. We also detected a significant increase in the proportion of moose ( Alces americanus ) cases diagnosed with P. tenuis , and this trend was consistent across endemic regions in Canada. Emerging diseases were also detected for the first time through our surveillance approach (e.g., the first Ontario cases of epizootic hemorrhagic disease virus, detected in white-tailed deer ( Odocoileus virginianus )). Trauma (15.3%) and emaciation (8.9%) were the most frequently assigned non-infectious CODs. We highlight potential disease threats to SAR that may emerge secondary to changing distributions of sympatric ungulate species and the pathogens they carry (e.g., CWD positive deer/elk within known caribou ranges in Saskatchewan). Our results highlight the strengths of passive disease surveillance, as well as the need for an integrated, holistic wildlife surveillance approach in Canada.
Journal Article
Aircraft Control and Simulation - Dynamics, Controls Design, and Autonomous Systems (3rd Edition)
This book is a comprehensive guide to aircraft control and simulation. This updated text covers flight control systems, flight dynamics, aircraft modeling, and flight simulation from both classical design and modern perspectives, as well as two new chapters on the modeling, simulation, and adaptive control of unmanned aerial vehicles. With detailed examples, including relevant MATLAB calculations and FORTRAN codes, this approachable yet detailed reference also provides access to supplementary materials, including chapter problems and an instructor's solution manual.Aircraft control, as a subject area, combines an understanding of aerodynamics with knowledge of the physical systems of an aircraft. The ability to analyze the performance of an aircraft both in the real world and in computer-simulated flight is essential to maintaining proper control and function of the aircraft. Keeping up with the skills necessary to perform this analysis is critical for you to thrive in the aircraft control field.
eBook
Manganese-Enhanced Magnetic Resonance Imaging Detects Declining Pancreatic β-Cell Mass in a Cyclophosphamide-Accelerated Mouse Model of Type 1 Diabetes
Currently, there is no ideal noninvasive method to quantify the progressive loss of pancreatic β-cell mass (BCM) that occurs in type 1 diabetes. Magnetic resonance imaging has detected gross differences in BCM between healthy and diabetic mice using the contrast agent manganese, which labels functional β-cells and increases the water proton relaxation rate (R1), but its ability to measure gradations in BCM during disease progression is unknown. Our objective was to test the hypothesis that measurements of the manganese-enhanced pancreatic R1 could detect decreasing BCM in a mouse model of type 1 diabetes. We used cyclophosphamide-accelerated BDC2.5 T-cell receptor transgenic nonobese diabetic mice, which experience development of type 1 diabetes during a 7-day time period after cyclophosphamide injection, whereas transgene-negative mice do not. We measured the manganese-enhanced pancreatic R1 before cyclophosphamide injection (day 0) and on days 3, 4, 5, and 7 afterward. Pancreatic R1 remained constant in transgene-negative mice and decreased stepwise day-to-day in transgene-positive mice, mirroring their loss of BCM, confirmed by pancreatic insulin measurements and histology. Changes in R1 in transgene-positive mice occurred before elevations in blood glucose, a clinical indicator of diabetes, suggesting potential for early noninvasive detection of changes in functional BCM.
Journal Article
A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology
The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand.
To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology.
Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months.
CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17).
CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients.
ClinicalTrials.gov NCT00556933.
Journal Article
Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes
Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes
Marcia McDuffie ,
Nelly A. Maybee ,
Susanna R. Keller ,
Brian K. Stevens ,
James C. Garmey ,
Margaret A. Morris ,
Elizabeth Kropf ,
Claudia Rival ,
Kaiwen Ma ,
Jeffrey D. Carter ,
Sarah A. Tersey ,
Craig S. Nunemaker and
Jerry L. Nadler
From the University of Virginia, Charlottesville, Virginia
Address correspondence and reprint requests to Jerry L. Nadler, MD, University of Virginia, P.O. Box 801405, Charlottesville,
VA 22908
Abstract
OBJECTIVE— 12/15-lipoxygenase (12/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to
produce proinflammatory lipids. 12/15-LO is expressed in macrophages and pancreatic β-cells. It enhances interleukin 12 production
by macrophages, and several of its products induce apoptosis of β-cells at nanomolar concentrations in vitro. We had previously
demonstrated a role for 12/15-LO in β-cell damage in the streptozotocin model of diabetes. Since the gene encoding 12/15-LO
(gene designation Alox15 ) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12/15-LO is also a key regulator of diabetes susceptibility
in the NOD mouse.
RESEARCH DESIGN AND METHODS— We developed NOD mice carrying an inactivated 12/15-LO locus (NOD- Alox15 null ) using a “speed congenic” protocol, and the mice were monitored for development of insulitis and diabetes.
RESULTS— NOD mice deficient in 12/15-LO develop diabetes at a markedly reduced rate compared with NOD mice (2.5 vs. >60% in females
by 30 weeks). Nondiabetic female NOD- Alox15 null mice demonstrate improved glucose tolerance, as well as significantly reduced severity of insulitis and improved β-cell mass,
when compared with age-matched nondiabetic NOD females. Disease resistance is associated with decreased numbers of islet-infiltrating
activated macrophages at 4 weeks of age in NOD- Alox15 null mice, preceding the development of insulitis. Subsequently, islet-associated infiltrates are characterized by decreased numbers
of CD4 + T cells and increased Foxp3 + cells.
CONCLUSIONS— These results suggest an important role for 12/15-LO in conferring susceptibility to autoimmune diabetes in NOD mice through
its effects on macrophage recruitment or activation.
EAE, experimental allergic encephalomyelitis
HETE, hydroxyeicosatetranoic acid
IL, interleukin
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 12 October 2007. DOI: 10.2337/db07-0830.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted October 9, 2007.
Received June 19, 2007.
DIABETES
Journal Article
Identification of a Novel Gammaherpesvirus in Canada lynx (Lynx canadensis)
Gammaherpesviruses (GHVs) infect many animal species and are associated with lymphoproliferative disorders in some. Previously, we identified several novel GHVs in North American felids; however, a GHV had never been identified in Canada lynx (Lynx canadensis). We, therefore, hypothesized the existence of an unidentified GHV in lynx. Using degenerate nested and subsequently virus-specific PCR, we amplified and sequenced 3.4 kb of DNA from a novel GHV in lynx, which we named Lynx canadensis gammaherpesvirus 1 (LcaGHV1). Phylogenetic analysis determined that LcaGHV1 is a distinct GHV species belonging to the genus Percavirus. We then estimated the prevalence of LcaGHV1 in lynx by developing a PCR-based assay and detected LcaGHV1 DNA in 36% (95% CI: 22–53%) of lynx spleen DNA samples from Maine, USA and 17% (95% CI: 8–31%) from Newfoundland, Canada. The LcaGHV1 DNA sequences from Maine and Newfoundland lynx were nearly identical to each other (two nucleotide substitutions in 3.4 kb), suggesting that the unique lynx subspecies present on the island of Newfoundland (Lynx canadensis subsolanus) is infected with virus that very closely resembles virus found in mainland lynx. The potential ecologic and pathologic consequences of this novel virus for Canada lynx populations warrant further study.
Journal Article
Interleukin‐2 is present in human blood vessels and released in biologically active form by heparanase
Interleukin‐2 (IL‐2) is a multifaceted cytokine with immunostimulatory and immunosuppressive properties. Our laboratory recently demonstrated that the availability of IL‐2 is regulated, in part, by association with perlecan, a heparan sulfate proteoglycan. Given the abundance of perlecan in blood vessels, we asked whether IL‐2 is present in vessel walls. Our results indicate that IL‐2 is associated with endothelial and smooth muscle cells within the human arterial wall. This IL‐2 is released by heparanase, and promotes the proliferation of an IL‐2‐dependent cell line. Given the presence of IL‐2 in human arteries, we asked whether the large vessels of IL‐2‐deficient mice were normal. The aortas of IL‐2‐deficient mice exhibited a loss of smooth muscle cells, suggesting that IL‐2 may contribute to their survival. In their entirety, these results suggest a here‐to‐fore unrecognized role of IL‐2 in vascular biology, and have significant implications for both the immune and cardiovascular systems.
Journal Article