86 results on '"Squires JR"'
Search Results
2. End-stage liver disease in children
- Author
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Squires, Jr, Robert H.
- Published
- 2001
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3. The Association Between Waist Circumference and FITNESSGRAM® Aerobic Capacity Classification in Sixth-Grade Children.
- Author
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Walker, John L., Murray, Tinker D., Eldridge, James, Squires Jr., William G., Silvius, Pete, and Silvius, Erik
- Subjects
CARDIOPULMONARY system ,STATISTICAL correlation ,EXERCISE tests ,LONGITUDINAL method ,PROBABILITY theory ,LOGISTIC regression analysis ,AEROBIC capacity ,PREDICTIVE tests ,RECEIVER operating characteristic curves ,WAIST circumference ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
The article discusses a study to determine the association between waist circumference (WC) and FiTNESSGRAM aerobic capacity criterion-referenced health fitness zone (HFZ) classification in 6th grade children. It cites findings that WC accounts for considerable variation in aerobic capacity and is significantly related to aerobic capacity classification based on FITNESSGRAM criterion standards.
- Published
- 2015
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4. The Oxygen Cost of a 20-Minute Steady-State Jog for High School Boys and Girls.
- Author
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Walker, John L., Murray, Tinker D., Johnson, Charles M., Rainey, Don L., and Squires, Jr., William G.
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PHYSICAL fitness for youth ,AEROBIC capacity ,EXERCISE tests ,MEDICAL function tests ,EXERCISE physiology ,TREADMILL exercise tests ,PHYSIOLOGICAL aspects of running ,HEALTH of high school students ,CALORIC expenditure ,SPORTS medicine ,CRITERION referenced tests - Abstract
This study evaluated the aerobic demands of the 20-minute steady-state jogging speeds for 15 high school students. All subjects performed a discontinuous treadmill test that included submaximal speeds, the Fit Youth Today criterion referenced speeds, and finally a run to voluntary fatigue. Stages lasted 5 minutes. Preliminary data indicated that both groups averaged between 87% (the 9 boys) and 93 % (the 6 girls) of their respective peak oxygen consumption at the criterion referenced speeds during treadmill testing. According to the American College of Sports Medicine guidelines for healthy adults, these intensities represent the upper threshold for aerobic conditioning, and high exercise intensities can increase the risk of injury. Although the results of this study are preliminary in nature and based on a small sample size, we suggest that the criterion referenced distances (speeds) for the FYT 20-minute steady-state jog may need modification. [ABSTRACT FROM AUTHOR]
- Published
- 1990
- Full Text
- View/download PDF
5. Book review
- Author
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Squires, Jr, Robert H.
- Published
- 1996
- Full Text
- View/download PDF
6. Waging the Wrong War: Drug War Strategy and Issues
- Author
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ARMY WAR COLL CARLISLE BARRACKS PA, Squires Jr.,, Malcolm H., Harris, Wayne C., Petoskey, Peter L., ARMY WAR COLL CARLISLE BARRACKS PA, Squires Jr.,, Malcolm H., Harris, Wayne C., and Petoskey, Peter L.
- Abstract
The war on drugs is disjointed and has evolved without a clear objective or center of gravity. Numerous agencies are pursuing different ends without a comprehensive, coordinated strategy. Competing national interests, legal restraints, confusing chains of command, interagency competition, political maneuvering, and wavering public interest have all contributed to complicating a workable strategy. The Department of Defense, as a major contributor in the war on drugs, has been assigned increasing responsibilities in the area of supply abatement--the area which our national leaders feel is most appropriate for the military. This study examines counternarcotics strategy from the perspectives of intelligence and law enforcement as these disciplines are affected by the law. After examining issues preventing drug war success, the study proposes a reorientation toward the true center of gravity--domestic demand reduction.
- Published
- 1992
7. Comparison of Academic and Behavioral Performance between Athletes and Non-athletes.
- Author
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ELDRIDGE, JAMES A., PALMER, TY B., GILLIS, KYLE, LLOYD, RICHARD, SQUIRES Jr., WILLIAM G., and MURRAY, TINKER D.
- Subjects
PHYSICAL fitness for youth ,ADOLESCENT health ,PHYSICAL activity ,SPORTS physiology - Abstract
The Toronto Charter for Physical Activity (2010) and several national physical activity plans advocate sports participation as an important part of population targeted physical activity for youth. Emerging research evidence also suggests that sports participation during adolescents is linked to significant positive correlations with academic and behavioral performance. The purpose of this study was to compare academic and behavioral performance between male and female public school athletes (Total N=11,139; 38% Female) and non-athletes (Total N=23,891; 52% Female) in a convenient, ethnicity diverse, sample (grades 7 -12) from the state of Texas (USA). We examined the passing rates of individual athletes and non-athletes on standardized tests (Texas Assessment of Knowledge and Skills, TAKS) for math, language arts, reading, writing, science, and social studies. We also examined the percentage of athletes and non-athletes for being "at risk," for dropping out of school and for the total average number of disciplinary actions. Chi-Square statistical analyses comparing athletes to non-athletes showed that athletes scored significantly better (p<0.05) on all standardized tests compared to non-athletes (passing rate ranges ranged from 77.1% to 92.9% versus 27.7% to 66.5% respectively). Athletes were at lower risk for dropout compared to non-athletes (35.6% versus 49.24%; p<0.05), and they had fewer disciplinary actions (mean of 0.85 per athletes per year versus 1.23 for non-athletes; ANOVA, p<0.05). Our results support the research findings of others that participation in school sports is positively correlated to better academic and behavioral performances for athletes compared to non-athletes. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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8. Chronic Abdominal Pain In Children: a Technical Report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
- Author
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Di Lorenzo, Carlo, Colletti, Richard B, Lehmann, Horald P, Boyle, John T, Gerson, William T, Hyams, Jeffrey S, Squires Jr., Robert H, Walker, Lynn S, Kanda, Pamela T, Squires, Robert H Jr, AAP Subcommittee, and NASPGHAN Committee on Chronic Abdominal Pain
- Abstract
Chronic abdominal pain, defined as long-lasting intermittent or constant abdominal pain, is a common pediatric problem encountered by primary care physicians, medical subspecialists and surgical specialists. Chronic abdominal pain in children is usually functional-that is, without objective evidence of an underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has prepared this report based on a comprehensive, systematic review and rating of the medical literature. This report accompanies a clinical report based on the literature review and expert opinion. The subcommittee examined the diagnostic and therapeutic value of a medical and psychologic history, diagnostic tests, and pharmacological and behavioral therapy. The presence of alarm symptoms or signs (such as weight loss, gastrointestinal bleeding, persistent fever, chronic severe diarrhea and significant vomiting) is associated with a higher prevalence of organic disease. There was insufficient evidence to state that the nature of the abdominal pain or the presence of associated symptoms (such as anorexia, nausea, headache and joint pain) can discriminate between functional and organic disorders. Although children with chronic abdominal pain and their parents are more often anxious or depressed, the presence of anxiety, depression, behavior problems or recent negative life events does not distinguish between functional and organic abdominal pain. Most children who are brought to the primary care physician's office for chronic abdominal pain are unlikely to require diagnostic testing. Pediatric studies of therapeutic interventions were examined and found to be limited or inconclusive. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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9. Chronic abdominal pain in children: a clinical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
- Author
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Di Lorenzo, Carlo, Colletti, Richard B, Lehmann, Harold P, Boyle, John T, Gerson, William T, Hyams, Jeffrey S, Squires Jr, Robert H, Walker, Lynn S, Kanda, Pamela T, Squires, Robert H Jr, American Academy of Pediatrics Subcommittee on Chronic Abdominal Pain, and NASPGHAN Committee on Abdominal Pain
- Abstract
Children and adolescents with chronic abdominal pain pose unique challenges to their caregivers. Affected children and their families experience distress and anxiety that can interfere with their ability to perform regular daily activities. Although chronic abdominal pain in children is usually attributable to a functional disorder rather than to organic disease, numerous misconceptions, insufficient knowledge among health care professionals and inadequate application of knowledge may contribute to a lack of effective management. This clinical report accompanies a technical report on childhood chronic abdominal pain and provides guidance for the clinician in the evaluation and treatment of children with chronic abdominal pain. The conclusions are based on the evidence reviewed in the technical report and on consensus achieved among subcommittee members. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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10. Correlation of Serum Cholylglycine Level with Hepatic Dysfunction in Children with Sickle Cell Anemia.
- Author
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Heubi, James E., Sayad, Alain E., Farah, Roula A., Rogers, Zora R., Buchanan, George R., and Squires Jr, Robert H.
- Subjects
SICKLE cell anemia in children ,ANEMIA in children ,GLYCINE ,THERAPEUTICS - Abstract
Presents information on a study which measures cholylglycine (CG) in young patients with sickle cell anemia. Methodology of the study; Results; Discussion on the study.
- Published
- 1999
11. Indications for pediatric gastrointestinal endoscopy: a medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition.
- Author
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Squires Jr., Robert H., Colletti, Richard B., Squires, R H Jr, and Colletti, R B
- Published
- 1996
12. Case Report Langerhans' Cell Histiocytosis Presenting with Hepatic Dysfunction.
- Author
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Squires Jr., Robert H., Weinberg, Arthur G., Zwiener, Robert J., and Winick, Naomi
- Published
- 1993
13. Intracranial Tumors.
- Author
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Squires Jr., Robert H.
- Subjects
INTRACRANIAL tumors ,NAUSEA ,DIAGNOSIS ,GASTROINTESTINAL system ,VOMITING in children ,CENTRAL nervous system ,NEUROLOGY - Abstract
Vomiting is seen as a symptom in patients with brain tumors, but it rarely leads to the diagnosis in the absence of a recognized neurologic deficit. Five patients were referred to a pediatric gastroenterologist for outpatient evaluation of persistent vomiting and were subsequently found to have an intracranial mass lesion. The paucity of neurologic findings and the absence of headaches in most of these patients caused the referring physicians to focus on the gastrointestinal tract and not the central nervous system as the cause of the patients' vomiting. The pathophysiology of vomiting and evaluation of these patients is discussed; recognizable patterns of vomiting in these patients are described. [ABSTRACT FROM AUTHOR]
- Published
- 1989
14. Gastrointestinal bleeding.
- Author
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Squires Jr, Robert H. and Squires, R H Jr
- Published
- 1999
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15. From whence does biliary atresia arise?
- Author
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Squires Jr., Robert H.
- Subjects
- *
CHOLESTASIS , *HEPATITIS in children , *HEPATITIS , *LIVER diseases , *VIRUS diseases , *OBSTRUCTIVE jaundice - Abstract
The article informs that biliary atresia, and its sister nemesis neonatal hepatitis, have been recognized as common causes of neonatal cholestasis for many years. Thirty years ago, the clinical description of idiopathic neonatal hepatitis was assigned to nearly 40% of infants with neonatal cholestasis. Over the last three decades of discovery, identification of patients with alpha-1 antityrpsin deficiency, neonatal iron storage disease, the family of disorders associated with progressive familial intrahepatic cholestasis, and newer viral infections such as parvovirus and HHV6 have whittled the diagnosis of idiopathic neonatal hepatitis to less than 20% of cases of neonatal cholestasis.
- Published
- 2005
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16. Participation in High School Sports and Student Academic Performance Outcomes.
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Murray, Tinker D. and Squires Jr., William G.
- Abstract
The article focuses on the association between participation in high school sports and academic performance outcomes of high school students in Texas. Studies suggest an improvement in education and health status of Texas students through participation in sports. It mentions the negative impact of being fat and unhealthy on academics, future life expectancy and the ability to compete in U.S. and global economies. It emphasizes the role of coaches in influencing athletic students.
- Published
- 2011
17. 2009-2010 Texas School Health and Physical Education Requirements Implications for Coaches.
- Author
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Murray, Tinker D. and Squires Jr., William
- Abstract
The article provides an overview of the 2009-2010 school health and physical education requirements in Texas and their implications to coaches. The requirements mentioned include meeting of the School Health Advisory Council (SHAC) at least four times every year, participation of students enrolled in a full-day pre-kindergarten in the moderate to vigorous physical activity (MVPA) for a minimum of 30 minutes daily, and giving the school districts authority to make health a local graduation requirement.
- Published
- 2009
18. Participation in High School Sports and Student Academic Performance Outcomes: Update 2012.
- Author
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Murray, Tinker D., Eldridge, James, and Squires Jr., William G.
- Abstract
The article presents an update on research concerning the relation between participation in high school sports and academic achievement. It summarizes findings of previous research which linked physical activity to improve in cognitive skills and classroom behavior. The research conducted by the Texas High School Coaches Educational Foundation (THSCEF) which reveals that athletes had significantly lower risk for dropping and disciplinary actions.
- Published
- 2012
19. PROFESSIONAL DEVELOPMENT COOPERATIVE.
- Author
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Murray, Tinker D., Power, Gene, and Squires Jr., William G.
- Abstract
The article focuses on the Professional Development Cooperative (PDC). The PDC was formed by the Texas High School Coaches Association (THSCA) in 2002 to provide coaches, who are also certified teachers in Texas, with continuing education opportunities. A historical overview of PDC, including its sessions at the annual THSCA meeting, is offered. The PDC future educational and research initiatives, which include research projects and educational seminars for 2009-2010, are also mentioned.
- Published
- 2009
20. SPORT PARTICIPATION PROMOTES POSITIVE YOUTH DEVELOPMENT.
- Author
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Murray, Tinker D. and Squires Jr., William G.
- Abstract
The article deals with the benefits of participating in sport. Due to their regular involvement in physical activities, through their training and competition experiences, it is likely that the vast majority of Texas students who are also participating in sports would score high on the FITNESSGRAM cardiovascular fitness assessments. It shows other findings from the March 2009 FITNESSGRAM data set which illustrated important connections between various physical fitness and academic performance.
- Published
- 2009
21. Senate Bill 530 and Fitness Testing.
- Author
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Murray, Tinker D. and Squires Jr., William G.
- Abstract
An excerpt from the U.S. Senate Bill 530, which deals with health and physical education and physical fitness assessment of students in middle schools.
- Published
- 2008
22. The Influence Of Bmi On One-mile Run And Pacer Performance In Sixth-grade Children.
- Author
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Murray, Tinker D., Walker, John L., Silvius, Pete, Silvius, Erik, Eldridge, James, and Squires Jr., William G.
- Published
- 2011
- Full Text
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23. The Effect Of Bmi And Waist Circumference On One-mile Run Performance In Sixth-graders.
- Author
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Walker, John L., Eldridge, James, Silvius, Pete, Silvius, Erik, Squires Jr., William G., and Muray, Tinker D.
- Published
- 2011
- Full Text
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24. THE ENERGY COST OF SUBMAXIMALWALKING AND RUNNING IN MODERATELY FIT ADULTS.
- Author
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Walker, J L., Neal, M A., Murray, T D., and Squires Jr., W G.
- Published
- 2002
25. Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease
- Author
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Robert Squires, Jr., MD
- Published
- 2019
26. N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure
- Author
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Robert Squires, Jr., MD
- Published
- 2016
27. Genetic connectivity of wolverines in western North America.
- Author
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Day CC, Landguth EL, Sawaya MA, Clevenger AP, Long RA, Holden ZA, Akins JR, Anderson RB, Aubry KB, Barrueto M, Bjornlie NL, Copeland JP, Fisher JT, Forshner A, Gude JA, Hausleitner D, Heim NA, Heinemeyer KS, Hubbs A, Inman RM, Jackson S, Jokinen M, Kluge NP, Kortello A, Lacroix DL, Lamar L, Larson LI, Lewis JC, Lockman D, Lucid MK, MacKay P, Magoun AJ, McLellan ML, Moriarty KM, Mosby CE, Mowat G, Nietvelt CG, Paetkau D, Palm EC, Paul KJS, Pilgrim KL, Raley CM, Schwartz MK, Scrafford MA, Squires JR, Walker ZJ, Waller JS, Weir RD, and Zeller KA
- Subjects
- Animals, Canada, Humans, Ecosystem, Mustelidae genetics, Genetics, Population, North America, Genotype, Genetic Variation, Microsatellite Repeats genetics
- Abstract
Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km
2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad-scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)- Published
- 2024
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28. Novel antibody language model accelerates IgG screening and design for broad-spectrum antiviral therapy.
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Almubarak HF, Tan W, Hoffmann AD, Sun Y, Wei J, El-Shennawy L, Squires JR, Dashzeveg NK, Simonton B, Jia Y, Iyer R, Xu Y, Nicolaescu V, Elli D, Randall GC, Schipma MJ, Swaminathan S, Ison MG, Liu H, Fang D, and Shen Y
- Abstract
Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline AbGen that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. Our AbGen centers around a novel antibody language model (AbLM) that is pretrained on 12 million generic protein domain sequences and fine-tuned on 4,000+ paired VH-VL sequences, with IgG-specific CDR-masking and VH-VL cross-attention. AbLM provides a latent space of IgG sequence embeddings for AbGen, including (a) landscapes of IgGs' activities in neutralizing the wild-type virus are analyzed through structure prediction for IgG and IgG-antigen (viral protein spike's receptor binding domain, RBD) interactions; and (b) landscapes of IgGs' susceptibility in neutralizing variant viruses are predicted through Gaussian process regression, despite that as few as 14 clinical antibodies' responses to variants of concern are available. The AbGen pipeline was applied to over 1300 IgG sequences we collected from RBD-binding B cells of convalescent patients. With experimental validations, AbGen efficiently prioritized IgG candidates against a broad spectrum of viral variants (wildtype, Delta, and Omicron), preventing the infection of host cells in vitro and hACE2 transgenic mice in vivo . Compared to other existing protein language models that require 10-100 times more model parameters, AbLM improved the precision from around 50% to 75% to predict IgGs with low variant susceptibility. Furthermore, AbGen enables structure-based computational protein redesign for selected IgG clones with single amino acid substitutions at the RBD-binding interface that doubled the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screen and re-design combining data-driven protein language models and Kriging for antibody sequence analysis and activity prediction, in synergy with physics-driven protein docking and design for antibody-antigen interface analyses and functional optimization., Competing Interests: Competing interest statement Northwestern University and H. L., D. F., L. E., A. D. H., and N. K. D. hold issued and/or provisional patents in IgG and exosome therapeutics. H.L., D. F., and A.D.H are scientific co-founders of ExoMira Medicine Inc.
- Published
- 2024
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29. Experimental recreationist noise alters behavior and space use of wildlife.
- Author
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Zeller KA, Ditmer MA, Squires JR, Rice WL, Wilder J, DeLong D, Egan A, Pennington N, Wang CA, Plucinski J, and Barber JR
- Subjects
- Animals, Behavior, Animal physiology, Animals, Wild physiology, Ecosystem, Noise adverse effects, Recreation
- Abstract
Providing outdoor recreational opportunities to people and protecting wildlife are dual goals of many land managers. However, recreation is associated with negative effects on wildlife, ranging from increased stress hormones
1 , 2 to shifts in habitat use3 , 4 , 5 to lowered reproductive success.6 , 7 Noise from recreational activities can be far reaching and have similar negative effects on wildlife, yet the impacts of these auditory encounters are less studied and are often unobservable. We designed a field-based experiment to both isolate and quantify the effects of recreation noise on several mammal species and test the effects of different recreation types and group sizes. Animals entering our sampling arrays triggered cameras to record video and broadcast recreation noise from speakers ∼20 m away. Our design allowed us to observe and classify behaviors of wildlife as they were exposed to acoustic stimuli. We found wildlife were 3.1-4.7 times more likely to flee and were vigilant for 2.2-3.0 times longer upon hearing recreation noise compared with controls (natural sounds and no noise). Wildlife abundance at our sampling arrays was 1.5 times lower the week following recreation noise deployments. Noise from larger groups of vocal hikers and mountain bikers caused the highest probability of fleeing (6-8 times more likely to flee). Elk were the most sensitive species to recreation noise, and large carnivores were the least sensitive. Our findings indicate that recreation noise alone caused anti-predator responses in wildlife, and as outdoor recreation continues to increase in popularity and geographic extent,8 , 9 noise from recreation may result in degraded or indirect wildlife habitat loss., Competing Interests: Declaration of interests Prefabricated BoomBox boards/kits used in this study can be obtained from FreakLabs (owned by J.P. and C.A.W.). However, the information necessary for building upon the hardware and software is available here and here., (Published by Elsevier Inc.)- Published
- 2024
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30. Novel polyomaviruses identified in fecal samples from four carnivore species.
- Author
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Kraberger S, Serieys LEK, Riley SPD, Schmidlin K, Newkirk ES, Squires JR, Buck CB, and Varsani A
- Subjects
- Rabbits, Animals, Cats, Humans, Swine, Phylogeny, Feces, Lynx, Polyomavirus genetics, Ursidae, Deer, Puma
- Abstract
Polyomaviruses are oncogenic viruses that are generally thought to have co-evolved with their hosts. While primate and rodent polyomaviruses are increasingly well-studied, less is known about polyomaviruses that infect other mammals. In an effort to gain insight into polyomaviruses associated with carnivores, we surveyed fecal samples collected in the USA from bobcats (Lynx rufus), pumas (Puma concolor), Canada lynxes (Lynx canadensis), and grizzly bears (Ursus arctos). Using a viral metagenomic approach, we identified six novel polyomavirus genomes. Surprisingly, four of the six genomes showed a phylogenetic relationship to polyomaviruses found in prey animals. These included a putative rabbit polyomavirus from a bobcat fecal sample and two possible deer-trophic polyomaviruses from Canada lynx feces. One polyomavirus found in a grizzly bear sample was found to be phylogenetically distant from previously identified polyomaviruses. Further analysis of the grizzly bear fecal sample showed that it contained anelloviruses that are known to infect pigs, suggesting that the bear might have preyed on a wild or domestic pig. Interestingly, a polyomavirus genome identified in a puma fecal sample was found to be closely related both to raccoon polyomavirus 1 and to Lyon-IARC polyomavirus, the latter of which was originally identified in human saliva and skin swab specimens but has since been found in samples from domestic cats (Felis catus)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
- Published
- 2023
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31. Complex evolutionary history of felid anelloviruses.
- Author
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Kraberger S, Serieys LE, Richet C, Fountain-Jones NM, Baele G, Bishop JM, Nehring M, Ivan JS, Newkirk ES, Squires JR, Lund MC, Riley SP, Wilmers CC, van Helden PD, Van Doorslaer K, Culver M, VandeWoude S, Martin DP, and Varsani A
- Subjects
- Anelloviridae classification, Animals, Biological Coevolution, Coinfection veterinary, Coinfection virology, DNA, Viral genetics, Felidae classification, Genetic Variation, Genome, Viral genetics, Open Reading Frames, Phylogeny, Recombination, Genetic, Sequence Analysis, DNA, Anelloviridae genetics, Felidae virology
- Abstract
Anellovirus infections are highly prevalent in mammals, however, prior to this study only a handful of anellovirus genomes had been identified in members of the Felidae family. Here we characterise anelloviruses in pumas (Puma concolor), bobcats (Lynx rufus), Canada lynx (Lynx canadensis), caracals (Caracal caracal) and domestic cats (Felis catus). The complete anellovirus genomes (n = 220) recovered from 149 individuals were diverse. ORF1 protein sequence similarity network analysis coupled with phylogenetic analysis, revealed two distinct clusters that are populated by felid-derived anellovirus sequences, a pattern mirroring that observed for the porcine anelloviruses. Of the two-felid dominant anellovirus groups, one includes sequences from bobcats, pumas, domestic cats and an ocelot, and the other includes sequences from caracals, Canada lynx, domestic cats and pumas. Coinfections of diverse anelloviruses appear to be common among the felids. Evidence of recombination, both within and between felid-specific anellovirus groups, supports a long coevolution history between host and virus., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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32. Improved prediction of Canada lynx distribution through regional model transferability and data efficiency.
- Author
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Olson LE, Bjornlie N, Hanvey G, Holbrook JD, Ivan JS, Jackson S, Kertson B, King T, Lucid M, Murray D, Naney R, Rohrer J, Scully A, Thornton D, Walker Z, and Squires JR
- Abstract
The application of species distribution models (SDMs) to areas outside of where a model was created allows informed decisions across large spatial scales, yet transferability remains a challenge in ecological modeling. We examined how regional variation in animal-environment relationships influenced model transferability for Canada lynx ( Lynx canadensis ), with an additional conservation aim of modeling lynx habitat across the northwestern United States. Simultaneously, we explored the effect of sample size from GPS data on SDM model performance and transferability. We used data from three geographically distinct Canada lynx populations in Washington ( n = 17 individuals), Montana ( n = 66), and Wyoming ( n = 10) from 1996 to 2015. We assessed regional variation in lynx-environment relationships between these three populations using principal components analysis (PCA). We used ensemble modeling to develop SDMs for each population and all populations combined and assessed model prediction and transferability for each model scenario using withheld data and an extensive independent dataset ( n = 650). Finally, we examined GPS data efficiency by testing models created with sample sizes of 5%-100% of the original datasets. PCA results indicated some differences in environmental characteristics between populations; models created from individual populations showed differential transferability based on the populations' similarity in PCA space. Despite population differences, a single model created from all populations performed as well, or better, than each individual population. Model performance was mostly insensitive to GPS sample size, with a plateau in predictive ability reached at ~30% of the total GPS dataset when initial sample size was large. Based on these results, we generated well-validated spatial predictions of Canada lynx distribution across a large portion of the species' southern range, with precipitation and temperature the primary environmental predictors in the model. We also demonstrated substantial redundancy in our large GPS dataset, with predictive performance insensitive to sample sizes above 30% of the original., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
- Published
- 2021
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33. Functional responses in habitat selection: clarifying hypotheses and interpretations.
- Author
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Holbrook JD, Olson LE, DeCesare NJ, Hebblewhite M, Squires JR, and Steenweg R
- Subjects
- Animal Distribution, Animals, Canada, Ecology, Ecosystem, Reindeer
- Abstract
A fundamental challenge in habitat ecology and management is understanding the mechanisms generating animal distributions. Studies of habitat selection provide a lens into such mechanisms, but are often limited by unrealistic assumptions. For example, most studies assume that habitat selection is constant with respect to the availability of resources, such that habitat use remains proportional to availability. To the contrary, a growing body of work has shown the fallacy of this assumption, indicating that animals modify their behavior depending on the context at broader scales. This has been termed a functional response in habitat selection. Furthermore, a diversity of methods is employed to model functional responses in habitat selection, with little attention to how methodology might affect scientific and conservation conclusions. Here, we first review the conceptual and statistical foundations of methods currently used to model functional responses and clarify the ecological tests evaluated within each approach. We then use a combination of simulated and empirical data sets to evaluate the similarities and differences among approaches. Importantly, we identified multiple statistical issues with the most widely applied approaches to understand functional responses, including: (1) a complex and important role of random- or individual-level intercepts in adjusting individual-level regression coefficients as resource availability changes and (2) a sensitivity of results to poorly informed individual-level coefficients estimated for animals with low availability of a given resource. Consequently, we provide guidance on applying approaches that are insensitive to these issues with the goal of advancing our understanding of animal habitat ecology and management. Finally, we characterize the management implications of assuming similarity between the current approaches to model functional responses with two empirical data sets of federally threatened species: Canada lynx (Lynx canadensis) in the United States and woodland caribou (Rangifer tarandus caribou) in Canada. Collectively, our assessment helps clarify the similarities and differences among current approaches and, therefore, assists the integration of functional responses into the mainstream of habitat ecology and management., (© 2019 by the Ecological Society of America.)
- Published
- 2019
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34. Survey design for broad-scale, territory-based occupancy monitoring of a raptor: Ferruginous hawk (Buteo regalis) as a case study.
- Author
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Johnson TN, Nasman K, Wallace ZP, Olson LE, Squires JR, Nielson RM, and Kennedy PL
- Subjects
- Algorithms, Animals, Computer Simulation, Conservation of Natural Resources, Ecosystem, Population Dynamics, Probability, Species Specificity, Wyoming, Ecology methods, Hawks physiology
- Abstract
Given the uncertain population status of low-density, widely-occurring raptors, monitoring changes in abundance and distribution is critical to conserving populations. Nest-based monitoring is a common, useful approach, but the difficulty and expense of monitoring raptor nests and importance of reliable trend data to conservation requires that limited resources are allocated efficiently. Power analyses offer a helpful tool to ensure that monitoring programs have the ability to detect trends and to optimize financial resources devoted to monitoring. We evaluated alternative monitoring designs for raptors to identify appropriate survey effort to detect population trends. We used data collected from a territory-occupancy study of ferruginous hawks throughout Wyoming to guide simulations and evaluate the ability to detect trends in occupancy rates. Results suggest that greater gains in precision of trend estimation may be achieved through the addition of more sites and not more visits; statistical power was ≥80% when monitoring lasted 20 years and population declines were 20%; and probability of detection affected statistical power less than rates of population decline. Monitoring at least 150 sites for 20 years would provide reasonable estimates of trend in occupancy given certain rates of detection and occupancy, but only for population declines of 20%. Removal sampling did not result in substantial changes of any metrics used to evaluate simulations, providing little justification for employing the standard design if territory occupancy is the variable of interest. Initial rates of territory occupancy may be biased high, a problem inherent to many studies that monitor territory occupancy. We explored the effects of lower rates of initial occupancy on the ability to detect trends. Although we present data from a study of ferruginous hawks, our simulations can be applied to other raptor species with similar life history and population dynamics to provide guidance for future trend estimation of territory occupancy., Competing Interests: K. Nasman is employed by Western Ecosystems Technology, Inc., as were T.N. Johnson (now employed by University of Idaho) and R.M. Nielson (now employed by Eagle Environmental, Inc.) at the time of this study. This affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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35. Sharing the same slope: Behavioral responses of a threatened mesocarnivore to motorized and nonmotorized winter recreation.
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Olson LE, Squires JR, Roberts EK, Ivan JS, and Hebblewhite M
- Abstract
Winter recreation is a widely popular activity and is expected to increase due to changes in recreation technology and human population growth. Wildlife are frequently negatively impacted by winter recreation, however, through displacement from habitat, alteration of activity patterns, or changes in movement behavior. We studied impacts of dispersed and developed winter recreation on Canada lynx ( Lynx canadensis ) at their southwestern range periphery in Colorado, USA. We used GPS collars to track movements of 18 adult lynx over 4 years, coupled with GPS devices that logged 2,839 unique recreation tracks to provide a detailed spatial estimate of recreation intensity. We assessed changes in lynx spatial and temporal patterns in response to motorized and nonmotorized recreation, as well as differences in movement rate and path tortuosity. We found that lynx decreased their movement rate in areas with high-intensity back-country skiing and snowmobiling, and adjusted their temporal patterns so that they were more active at night in areas with high-intensity recreation. We did not find consistent evidence of spatial avoidance of recreation: lynx exhibited some avoidance of areas with motorized recreation, but selected areas in close proximity to nonmotorized recreation trails. Lynx appeared to avoid high-intensity developed ski resorts, however, especially when recreation was most intense. We conclude that lynx in our study areas did not exhibit strong negative responses to dispersed recreation, but instead altered their behavior and temporal patterns in a nuanced response to recreation, perhaps to decrease direct interactions with recreationists. However, based on observed avoidance of developed recreation, there may be a threshold of human disturbance above which lynx cannot coexist with winter recreation.
- Published
- 2018
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36. Forest structure provides the income for reproductive success in a southern population of Canada lynx.
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Kosterman MK, Squires JR, Holbrook JD, Pletscher DH, and Hebblewhite M
- Subjects
- Animals, Female, Food, Life History Traits, Montana, Spatial Analysis, Forests, Lynx, Reproduction
- Abstract
Understanding intrinsic and extrinsic drivers of reproductive success is central to advancing animal ecology and characterizing critical habitat. Unfortunately, much of the work examining drivers of reproductive success is biased toward particular groups of organisms (e.g., colonial birds, large herbivores, capital breeders). Long-lived mammalian carnivores that are of conservation concern, solitary, and territorial present an excellent situation to examine intrinsic and extrinsic drivers of reproductive success, yet they have received little attention. Here, we used a Canada lynx (Lynx canadensis) data set, from the southern periphery of their range, to determine if reproductive success in a solitary carnivore was consistent with capital or income breeding. We radio-marked and monitored 36 female Canada lynx for 98 lynx years. We evaluated how maternal characteristics and indices of food supply (via forest structure) in core areas influenced variation in body condition and reproductive success. We characterized body condition as mass/length and reproductive success as whether a female produced a litter of kittens for a given breeding season. Consistent with life-history theory, we documented a positive effect of maternal age on body condition and reproductive success. In contrast to predictions of capital breeding, we observed no effect of pre-pregnancy body condition on reproductive success in Canada lynx. However, we demonstrated statistical effects of forest structure on reproductive success in Canada lynx, consistent with predictions of income breeding. The forest characteristics that defined high success included (1) abundant and connected mature forest and (2) intermediate amounts of small-diameter regenerating forest. These attributes are consistent with providing abundant, temporally stable, and accessible prey resources (i.e., snowshoe hares; Lepus americanus) for lynx and reinforce the bottom-up mechanisms influencing Canada lynx populations. Collectively, our results suggest that lynx on the southern range periphery exhibit an income breeding strategy and that forest structure supplies the income important for successful reproduction. More broadly, our insights advance the understanding of carnivore ecology and serve as an important example on integrating long-term field studies with ecological theory to improve landscape management., (© 2018 by the Ecological Society of America.)
- Published
- 2018
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37. Predicting above-ground density and distribution of small mammal prey species at large spatial scales.
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Olson LE, Squires JR, Oakleaf RJ, Wallace ZP, and Kennedy PL
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- Animals, Environment, Models, Theoretical, Population Density, Predatory Behavior, Spatial Analysis, Wyoming, Ecosystem, Mammals
- Abstract
Grassland and shrub-steppe ecosystems are increasingly threatened by anthropogenic activities. Loss of native habitats may negatively impact important small mammal prey species. Little information, however, is available on the impact of habitat variability on density of small mammal prey species at broad spatial scales. We examined the relationship between small mammal density and remotely-sensed environmental covariates in shrub-steppe and grassland ecosystems in Wyoming, USA. We sampled four sciurid and leporid species groups using line transect methods, and used hierarchical distance-sampling to model density in response to variation in vegetation, climate, topographic, and anthropogenic variables, while accounting for variation in detection probability. We created spatial predictions of each species' density and distribution. Sciurid and leporid species exhibited mixed responses to vegetation, such that changes to native habitat will likely affect prey species differently. Density of white-tailed prairie dogs (Cynomys leucurus), Wyoming ground squirrels (Urocitellus elegans), and leporids correlated negatively with proportion of shrub or sagebrush cover and positively with herbaceous cover or bare ground, whereas least chipmunks showed a positive correlation with shrub cover and a negative correlation with herbaceous cover. Spatial predictions from our models provide a landscape-scale metric of above-ground prey density, which will facilitate the development of conservation plans for these taxa and their predators at spatial scales relevant to management.
- Published
- 2017
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38. Does Zoning Winter Recreationists Reduce Recreation Conflict?
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Miller AD, Vaske JJ, Squires JR, Olson LE, and Roberts EK
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- Colorado, Geographic Information Systems, Humans, Interpersonal Relations, Surveys and Questionnaires, Travel psychology, Conflict, Psychological, Conservation of Natural Resources methods, Recreation psychology, Seasons, Snow Sports psychology
- Abstract
Parks and protected area managers use zoning to decrease interpersonal conflict between recreationists. Zoning, or segregation, of recreation-often by non-motorized and motorized activity-is designed to limit physical interaction while providing recreation opportunities to both groups. This article investigated the effectiveness of zoning to reduce recreation conflict in the Vail Pass Winter Recreation Area in Colorado, USA. Despite a zoning management system, established groomed travel routes were used by both non-motorized recreationists (backcountry skiers, snowboarders, snowshoers) and motorized recreationists (snowmobilers). We hypothesized that persistent recreation conflict reported by non-motorized recreationists was the result of recreation occurring in areas of mixed non-motorized and motorized use, mostly along groomed routes. We performed a geospatial analysis of recreation [from Global Positioning System (GPS) points, n = 1,233,449] in the Vail Pass Winter Recreation Area to identify areas of mixed non-motorized and motorized use. We then surveyed non-motorized recreationists (n = 199) to test whether reported conflict is higher for respondents who traveled in areas of mixed-use, compared with respondents traveling outside areas of mixed-use. Results from the geospatial analysis showed that only 0.7 % of the Vail Pass Winter Recreation Area contained recreation from both groups, however that area contained 14.8 % of all non-motorized recreation and 49.1 % of all motorized recreation. Survey analysis results showed higher interpersonal conflict for all five standard conflict variables among non-motorized respondents who traveled in areas of mixed-use, compared with those traveling outside mixed-use areas. Management implications and recommendations for increasing the effectiveness of zoning are provided.
- Published
- 2017
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39. Multiscale habitat relationships of snowshoe hares ( Lepus americanus ) in the mixed conifer landscape of the Northern Rockies, USA: Cross-scale effects of horizontal cover with implications for forest management.
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Holbrook JD, Squires JR, Olson LE, Lawrence RL, and Savage SL
- Abstract
Snowshoe hares ( Lepus americanus ) are an ecologically important herbivore because they modify vegetation through browsing and serve as a prey resource for multiple predators. We implemented a multiscale approach to characterize habitat relationships for snowshoe hares across the mixed conifer landscape of the northern Rocky Mountains, USA. Our objectives were to (1) assess the relationship between horizontal cover and snowshoe hares, (2) estimate how forest metrics vary across the gradient of snowshoe hare use and horizontal cover, and (3) model and map snowshoe hare occupancy and intensity of use. Results indicated that both occupancy and intensity of use by snowshoe hares increased with horizontal cover and that the effect became stronger as intensity of use increased. This underscores the importance of dense horizontal cover to achieve high use, and likely density, of snowshoe hares. Forest structure in areas with high snowshoe hare use and horizontal cover was characterized as multistoried with dense canopy cover and medium-sized trees (e.g., 12.7-24.4 cm). The abundance of lodgepole pine ( Pinus contorta ) was associated with snowshoe hare use within a mixed conifer context, and the only species to increase in abundance with horizontal cover was Engelmann spruce ( Picea engelmannii ) and subalpine fir ( Abies lasiocarpa ). Our landscape-level modeling produced similar patterns in that we observed a positive effect of lodgepole pine and horizontal cover on both occupancy and use by snowshoe hares, but we also observed a positive yet parabolic effect of snow depth on snowshoe hare occupancy. This work is among the first to characterize the multiscale habitat relationships of snowshoe hares across a mixed conifer landscape as well as to map their occupancy and intensity of use. Moreover, our results provide stand- and landscape-level insights that directly relate to management agencies, which aids in conservation efforts of snowshoe hares and their associated predators.
- Published
- 2016
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40. Re-Occupancy of Breeding Territories by Ferruginous Hawks in Wyoming: Relationships to Environmental and Anthropogenic Factors.
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Wallace ZP, Kennedy PL, Squires JR, Oakleaf RJ, Olson LE, and Dugger KM
- Subjects
- Animals, Probability, Wyoming, Breeding, Ecosystem, Hawks physiology
- Abstract
Grassland and shrubland birds are declining globally due in part to anthropogenic habitat modification. Because population performance of these species is also influenced by non-anthropogenic factors, it is important to incorporate all relevant ecological drivers into demographic models. We used design-based sampling and occupancy models to test relationships of environmental factors that influence raptor demographics with re-occupancy of breeding territories by ferruginous hawks (Buteo regalis) across Wyoming, USA, 2011-2013. We also tested correlations of territory re-occupancy with oil and gas infrastructure-a leading cause of habitat modification throughout the range of this species of conservation concern. Probability of re-occupancy was not related to any covariates we investigated in 2011, had a strong negative relationship with cover of sagebrush (Artemisia spp.) in 2012, was slightly higher for territories with artificial platforms than other nest substrates in 2013, and had a positive relationship with abundance of ground squirrels (Urocitellus spp.) that was strong in 2012 and weak in 2013. Associations with roads were weak and varied by year, road-type, and scale: in 2012, re-occupancy probability had a weak positive correlation with density of roads not associated with oil and gas fields at the territory-scale; however, in 2013 re-occupancy had a very weak negative correlation with density of oil and gas field roads near nest sites (≤500 m). Although our results indicate re-occupancy of breeding territories by ferruginous hawks was compatible with densities of anthropogenic infrastructure in our study area, the lack of relationships between oil and gas well density and territory re-occupancy may have occurred because pre-treatment data were unavailable. We used probabilistic sampling at a broad spatial extent, methods to account for imperfect detection, and conducted extensive prey sampling; nonetheless, future research using before-after-control-impact designs is needed to fully assess impacts of oil and gas development on ferruginous hawks.
- Published
- 2016
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41. Prognostic scoring indices in Wilson disease: a case series and cautionary tale.
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Fischer RT, Soltys KA, Squires RH Jr, Jaffe R, Mazariegos GV, and Shneider BL
- Subjects
- Adolescent, Child, Female, Hepatolenticular Degeneration surgery, Humans, Liver Cirrhosis etiology, Liver Failure etiology, Liver Transplantation, Male, Prognosis, Severity of Illness Index, Treatment Outcome, Hepatolenticular Degeneration diagnosis, Hepatolenticular Degeneration physiopathology
- Abstract
Objectives: In children with acute presentations of Wilson disease (WD), liver transplantation may be the only effective therapy. The Wilson Index is a prognostic index used to determine the risk of death without transplant in WD. We sought to determine the accuracy of this system in our own patient population., Patients and Methods: The clinical course of patients diagnosed as having acute WD seen at the Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center between 2003 and 2008 was reviewed., Results: Six patients were identified; their index scores ranged from 7 to 13, with 3 patients receiving a score predictive of death without transplantation (≥ 10). Of those 3, 1 underwent transplantation and 2 survived without transplant. The latter 2 have been removed from the transplant waitlist. In all, 5 patients were listed for transplantation, and 2 of the 5 received prioritized status 1A listing. Only 2 of the 5 patients went to transplantation, and neither was status 1A at the time of transplant., Conclusions: Prognostic scoring systems, although useful, may not be entirely accurate. Likewise, aggressive utilization of status 1 prioritization may result in unnecessary transplants and misallocation of a rare resource. However, deferring status 1 prioritization may yield an incomplete response to therapy and preclude lifesaving transplantation. Continued investigation of predictors of outcome in WD is necessary.
- Published
- 2011
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42. Patterns of ovarian and luteal activity in captive and wild Canada lynx (Lynx canadensis).
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Fanson KV, Wielebnowski NC, Shenk TM, Vashon JH, Squires JR, and Lucas JR
- Subjects
- Animals, Animals, Wild physiology, Animals, Zoo physiology, Breeding, Estrogens metabolism, Feces chemistry, Female, Ovulation physiology, Progesterone metabolism, Seasons, Corpus Luteum physiology, Lynx physiology, Ovary physiology
- Abstract
Canada lynx face some unique breeding restrictions, which may have implications for population viability and captive management. The goal of this study was to improve our understanding of basic reproductive physiology in Canada lynx. Using fecal hormone metabolite analysis, we established normative patterns of fecal estrogen (fE) and progestagen (fP) expression in captive and wild female Canada lynx. Our results indicate that Canada lynx have persistent corpora lutea, which underlie their uncharacteristic fP profiles compared to other felids. Thus, fP are not useful for diagnosing pregnancy in Canada lynx. We also found that Canada lynx are capable of ovulating spontaneously. Captive females had higher concentrations of fE and fP than wild females. Both populations exhibit a seasonal increase in ovarian activity (as measured by fE) between February and April. Finally, there was evidence of ovarian suppression when females were housed together., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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43. Patterns of testicular activity in captive and wild Canada lynx (Lynx canadensis).
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Fanson KV, Wielebnowski NC, Shenk TM, Jakubas WJ, Squires JR, and Lucas JR
- Subjects
- Animals, Animals, Wild physiology, Animals, Zoo physiology, Breeding, Endangered Species, Feces chemistry, Housing, Animal, Male, Orchiectomy, Seasons, Androgens metabolism, Lynx metabolism, Testis physiology
- Abstract
Canada lynx are listed as a threatened species in the contiguous US. Understanding the reproductive characteristics (i.e., mating system, behavior, physiology) of a species is useful for ensuring effective in situ and ex situ management plans. The goal of this study was to describe patterns of androgen expression in both captive and wild male Canada lynx using fecal hormone metabolite analysis. Among captive lynx, juvenile and castrated males had lower concentrations of fecal androgens (fA) than intact males, thereby demonstrating that the assay detects biologically meaningful differences in testicular activity. We found that captive males in general had much higher fA levels than wild males. All males showed strong seasonal variation in fA concentrations, with significantly higher levels being expressed during the breeding season (February and March) than during the non-breeding season. Among captive males, variation in seasonal fA levels did not correlate with latitude. Finally, males housed with intact cage-mates (either male or female) had significantly higher fA levels than males housed alone or with a neutered cage-mate., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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44. Munchausen syndrome by proxy: ongoing clinical challenges.
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Squires JE and Squires RH Jr
- Subjects
- Adult, Child, Clinical Competence, Diagnosis, Differential, Disease Management, Factitious Disorders, Female, Humans, Male, Munchausen Syndrome by Proxy epidemiology, Parents psychology, Munchausen Syndrome by Proxy diagnosis, Physician's Role
- Abstract
In 1977, Roy Meadow, a pediatric nephrologist, first described a condition he subsequently coined Munchausen syndrome by proxy. The classic form involves a parent or other caregiver who inflicts injury or induces illness in a child, deceive the treating physician with fictitious or exaggerated information, and perpetrate the trick for months or years. A related form of pathology is more insidious and more common but also damaging. It involves parents who fabricate or exaggerate symptoms of illness in children, causing overly aggressive medical evaluations and interventions. The common thread is that the treating physician plays a role in inflicting the abuse upon the child. Failure to recognize the problem is common because the condition is often not included in the differential diagnosis of challenging or confusing clinical problems. We believe that a heightened "self-awareness" of the physician's role in Munchausen syndrome by proxy will prevent or reduce the morbidity and mortality associated with this diagnosis. In addition, we believe contemporary developments within the modern health care system likely facilitate this condition.
- Published
- 2010
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45. Translational systems approaches to the biology of inflammation and healing.
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Vodovotz Y, Constantine G, Faeder J, Mi Q, Rubin J, Bartels J, Sarkar J, Squires RH Jr, Okonkwo DO, Gerlach J, Zamora R, Luckhart S, Ermentrout B, and An G
- Subjects
- Animals, Clinical Trials as Topic, Cytokines immunology, Disease Models, Animal, Humans, Inflammation etiology, Models, Biological, Systems Biology, Wound Healing immunology
- Abstract
Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
- Published
- 2010
- Full Text
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46. Wolverine gene flow across a narrow climatic niche.
- Author
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Schwartz MK, Copeland JP, Anderson NJ, Squires JR, Inman RM, McKelvey KS, Pilgrim KL, Waits LP, and Cushman SA
- Subjects
- Animals, Demography, Ecosystem, Genetic Variation, Idaho, Montana, Seasons, Wyoming, Climate, Gene Flow, Mustelidae genetics
- Abstract
Wolverines (Gulo gulo) are one of the rarest carnivores in the contiguous United States. Effective population sizes in Montana, Idaho, and Wyoming, where most of the wolverines in the contiguous United States exist, were calculated to be 35 (credible limits, 28 52) suggesting low abundance. Landscape features that influence wolverine population substructure and gene flow are largely unknown. Recent work has identified strong associations between areas with persistent spring snow and wolverine presence and range. We tested whether a dispersal model in which wolverines prefer to disperse through areas characterized by persistent spring snow cover produced least-cost paths among all individuals that correlated with genetic distance among individuals. Models simulating large preferences for dispersing within areas characterized by persistent spring snow explained the data better than a model based on Euclidean distance. Partial Mantel tests separating Euclidean distance from spring snow-cover-based effects indicated that Euclidean distance was not significant in describing patterns of genetic distance. Because these models indicated that successful dispersal paths followed areas characterized by spring snow cover, we used these understandings to derive empirically based least-cost corridor maps in the U.S. Rocky Mountains. These corridor maps largely explain previously published population subdivision patterns based on mitochondrial DNA and indicate that natural colonization of the southern Rocky Mountains by wolverines will be difficult but not impossible.
- Published
- 2009
- Full Text
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47. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests.
- Author
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Korman JD, Volenberg I, Balko J, Webster J, Schiodt FV, Squires RH Jr, Fontana RJ, Lee WM, and Schilsky ML
- Subjects
- Adolescent, Adult, Alanine Transaminase blood, Alkaline Phosphatase blood, Aspartate Aminotransferases blood, Bilirubin blood, Biomarkers blood, Ceruloplasmin metabolism, Copper metabolism, Diagnosis, Differential, Female, Hepatolenticular Degeneration blood, Humans, Liver Failure, Acute blood, Male, Middle Aged, Sensitivity and Specificity, Diagnostic Tests, Routine methods, Hepatolenticular Degeneration complications, Hepatolenticular Degeneration diagnosis, Liver Failure, Acute diagnosis, Liver Failure, Acute etiology
- Abstract
Unlabelled: Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp <20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 microg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio >2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%., Conclusion: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.
- Published
- 2008
- Full Text
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48. Acute liver failure in children.
- Author
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Squires RH Jr
- Subjects
- Acetaminophen adverse effects, Adrenal Cortex Hormones therapeutic use, Analgesics, Non-Narcotic adverse effects, Child, Drug-Related Side Effects and Adverse Reactions, Humans, Immunologic Deficiency Syndromes complications, Infections complications, Liver Transplantation, Metabolism, Inborn Errors complications, Phytotherapy adverse effects, Plasma Exchange, Plasmapheresis, Poisons adverse effects, Renal Dialysis, Liver Failure, Acute etiology, Liver Failure, Acute therapy
- Abstract
Acute liver failure (ALF) in children differs from that observed in adults in both the etiologic spectrum and the clinical picture. Children, particularly very young ones, do not demonstrate classical features of encephalopathy and the definition of ALF has been revised to include patients with advanced coagulopathy, regardless of mental status. A significant number of these children will go on to require transplant or die. Etiologies vary by age with metabolic and infectious diseases prominent in the first year of life and acetaminophen overdose and Wilson's disease occurring in adolescents. In almost 50% of cases, however, the child has an indeterminate cause for ALF. Management requires a multidisciplinary approach and is directed at establishing the etiology where possible and monitoring, anticipating, and managing the multisystem complications that occur in children with ALF. Overall, short-term outcomes are better in children than adults but are dependent upon the degree of encephalopathy and diagnosis.
- Published
- 2008
- Full Text
- View/download PDF
49. Acute liver failure: Summary of a workshop.
- Author
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Lee WM, Squires RH Jr, Nyberg SL, Doo E, and Hoofnagle JH
- Subjects
- Acetaminophen adverse effects, Adult, Analgesics, Non-Narcotic adverse effects, Child, Humans, Liver Failure, Acute therapy, Liver Transplantation, Liver Failure, Acute etiology
- Abstract
Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.
- Published
- 2008
- Full Text
- View/download PDF
50. Bile acylcarnitine profiles in pediatric liver disease do not interfere with the diagnosis of long-chain fatty acid oxidation defects.
- Author
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Fuda F, Narayan SB, Squires RH Jr, and Bennett MJ
- Subjects
- Biopsy, Carnitine metabolism, Humans, Infant, Oxidation-Reduction, Bile metabolism, Carnitine analogs & derivatives, Fatty Acids chemistry, Fatty Acids metabolism, Liver Diseases diagnosis, Liver Diseases metabolism
- Abstract
Background: Plasma acylcarnitine measurement is an important diagnostic tool for inherited disorders of fatty acid and organic acid metabolism. Biliary excretion has been shown to be the primary route of excretion for acylcarnitines and analysis of bile acylcarnitine profiles may provide greater sensitivity for detecting metabolic disorders. Disorders of fatty acid oxidation frequently present with deranged liver function and the effect of hepatic disease on biliary acylcarnitine excretion are unknown., Methods: We measured biliary acylcarnitine levels in pediatric patients aged 6 months to 1 year undergoing open liver biopsy with prospectively determined non-metabolic liver disease in order to determine the effect of the liver disease on acylcarnitine excretion. Bile was collected in syringes and was transported immediately and stored at -70 degrees C until the time of testing. The disease patient population consisted of 2 patients with known defects in long- and short-chain fatty acid oxidation (long-chain L-3-hydroxy acyl-CoA dehydrogenase: LCHAD and short-chain L-3-hydroxy acyl-CoA dehydrogenase: SCHAD). The sample from the LCHAD patient was collected at autopsy and the patient with SCHAD deficiency was subsequently diagnosed as part of the prospective study and removed from the unknown etiology group. Acylcarnitine profiles were obtained for each specimen as butylated derivatives using tandem mass spectrometry., Results: The non-metabolic liver disease had no effect on the diagnostic value of bile acylcarnitine levels for detecting LCHAD deficiency. The concentrations of bile long-chain acylcarnitine species analyzed from patients with non-metabolic liver disease were far lower than the levels seen in LCHAD deficiency which also demonstrated a characteristic pattern of 3-hydroxyacylcarnitine excretion. In SCHAD deficiency, for which pathognomonic markers have not yet been established, bile analysis did not improve the diagnostic ability., Conclusion: The analysis of bile acylcarnitines for the diagnosis of long-chain fatty acid oxidation defects will provide unbiased information even in the presence of severe non-metabolic liver disease.
- Published
- 2006
- Full Text
- View/download PDF
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