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338 The Alabama Genomic Health Initiative: Integrating Genomic Medicine into Primary Care
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- Nita A Limdi, Devin Absher, Irf Asif, Lori Bateman, Greg Barsh, Kevin M. Bowling, Gregory M. Cooper, Brittney H. Davis, Kelly M. East, Candice R. Finnila, Blake Goff, Susan Hiatt, Melissa Kelly, Whitley V. Kelley, Bruce R. Korf, Donald R. Latner, James Lawlor, Thomas May, Matt Might, Irene P. Moss, Mariko Nakano-Okuno, Tiffany Osborne, Stephen Sodeke, Adriana Stout, Michelle L. Thompson
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 100-101
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OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
Evaluation of 2,4-D–based Herbicide Mixtures for Control of Glyphosate-Resistant Palmer Amaranth (Amaranthus palmeri)
- Benjamin H. Lawrence, Jason A. Bond, Thomas W. Eubank, Bobby R. Golden, Donald R. Cook, Joseph P. Mangialardi
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- Journal:
- Weed Technology / Volume 33 / Issue 2 / April 2019
- Published online by Cambridge University Press:
- 06 December 2018, pp. 263-271
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Understanding control of glyphosate-resistant (GR) Palmer amaranth with multiple herbicide sites of action, including synthetic auxins, is crucial for growers to minimize GR Palmer amaranth interference with crops. Field studies in 2013 and 2014 and a greenhouse study in 2014 were conducted in Stoneville, MS, to evaluate POST control of GR Palmer amaranth with 2,4-D alone and in mixtures with glyphosate and/or glufosinate. In the greenhouse study, control of 5- and 10-cm GR Palmer amaranth was 87% with 2,4-D at 0.84 kg ae ha−1. Dry weight reduction of GR Palmer amaranth was ≥81% with 2,4-D at 0.84 kg ha−1. In field studies, mixtures of glufosinate at 0.59 kg ai ha−1 and 2,4-D at 0.56 or 1.12 kg ae ha−1 controlled 5- to 10-cm GR Palmer amaranth 87% at 28 d after treatment (DAT). Averaged across glyphosate treatments, glufosinate applied alone applied to 5- to 10-cm GR Palmer amaranth reduced dry weight at 28 DAT to 20 g m−2 from 82 g m−2 and was comparable with that following 2,4-D applied alone at 1.12 kg ae ha−1 and mixtures of glufosinate plus 2,4-D at 0.56 and 1.12 kg ae ha−1. Mixtures of 2,4-D plus glufosinate provided ≥92% control of 15- to 20-cm GR Palmer amaranth at 28 DAT. When applied to 15- to 20-cm plants, mixtures of 2,4-D plus glufosinate reduced GR Palmer amaranth density to ≤5 plants m−2 compared with 65 plants m−2 where no 2,4-D or glufosinate was applied. Glufosinate and 2,4-D are viable control options for 5- to 10-cm or 15- to 20-cm GR Palmer amaranth. However, 2,4-D did not improve GR Palmer amaranth control when added to any herbicide mixture except glyphosate and glufosinate applied to 15- to 20-cm plants at the 28 DAT evaluation.
Important Bird and Biodiversity Areas (IBAs): the development and characteristics of a global inventory of key sites for biodiversity
- PAUL F. DONALD, LINCOLN D. C. FISHPOOL, ADEMOLA AJAGBE, LEON A. BENNUN, GILL BUNTING, IAN J. BURFIELD, STUART H. M. BUTCHART, SOFIA CAPELLAN, MICHAEL J. CROSBY, MARIA P. DIAS, DAVID DIAZ, MICHAEL I. EVANS, RICHARD GRIMMETT, MELANIE HEATH, VICTORIA R. JONES, BENJAMIN G. LASCELLES, JENNIFER C. MERRIMAN, MARK O’BRIEN, IVÁN RAMÍREZ, ZOLTAN WALICZKY, DAVID C. WEGE
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- Journal:
- Bird Conservation International / Volume 29 / Issue 2 / June 2019
- Published online by Cambridge University Press:
- 23 October 2018, pp. 177-198
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Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Important Bird and Biodiversity Areas (IBAs): their impact on conservation policy, advocacy and action
- ZOLTAN WALICZKY, LINCOLN D. C. FISHPOOL, STUART H. M. BUTCHART, DAVID THOMAS, MELANIE F. HEATH, CAROLINA HAZIN, PAUL F. DONALD, AIDA KOWALSKA, MARIA P. DIAS, TRISTRAM S. M. ALLINSON
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- Journal:
- Bird Conservation International / Volume 29 / Issue 2 / June 2019
- Published online by Cambridge University Press:
- 23 October 2018, pp. 199-215
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BirdLife International´s Important Bird and Biodiversity Areas (IBA) Programme has identified, documented and mapped over 13,000 sites of international importance for birds. IBAs have been influential with governments, multilateral agreements, businesses and others in: (1) informing governments’ efforts to expand protected area networks (in particular to meet their commitments through the Convention on Biological Diversity); (2) supporting the identification of Ecologically or Biologically Significant Areas (EBSAs) in the marine realm, (3) identifying Wetlands of International Importance under the Ramsar Convention; (4) identifying sites of importance for species under the Convention on Migratory Species and its sister agreements; (5) identifying Special Protected Areas under the EU Birds Directive; (6) applying the environmental safeguards of international finance institutions such as the International Finance Corporation; (7) supporting the private sector to manage environmental risk in its operations; and (8) helping donor organisations like the Critical Ecosystems Partnership Fund (CEPF) to prioritise investment in site-based conservation. The identification of IBAs (and IBAs in Danger: the most threatened of these) has also triggered conservation and management actions at site level, most notably by civil society organisations and local conservation groups. IBA data have therefore been widely used by stakeholders at different levels to help conserve a network of sites essential to maintaining the populations and habitats of birds as well as other biodiversity. The experience of IBA identification and conservation is shaping the design and implementation of the recently launched Key Biodiversity Areas (KBA) Partnership and programme, as IBAs form a core part of the KBA network.
Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study
- Felicia M. Mix, Martin D. Zielinski, Lucas A. Myers, Kathy S. Berns, Anurahda Luke, James R. Stubbs, Scott P. Zietlow, Donald H. Jenkins, Matthew D. Sztajnkrycer
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- Prehospital and Disaster Medicine / Volume 33 / Issue 3 / June 2018
- Published online by Cambridge University Press:
- 19 April 2018, pp. 230-236
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- June 2018
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Introduction
Hemorrhage remains the major cause of preventable death after trauma. Recent data suggest that earlier blood product administration may improve outcomes. The purpose of this study was to determine whether opportunities exist for blood product transfusion by ground Emergency Medical Services (EMS).
MethodsThis was a single EMS agency retrospective study of ground and helicopter responses from January 1, 2011 through December 31, 2015 for adult trauma patients transported from the scene of injury who met predetermined hemodynamic (HD) parameters for potential transfusion (heart rate [HR]≥120 and/or systolic blood pressure [SBP]≤90).
ResultsA total of 7,900 scene trauma ground transports occurred during the study period. Of 420 patients meeting HD criteria for transfusion, 53 (12.6%) had a significant mechanism of injury (MOI). Outcome data were available for 51 patients; 17 received blood products during their emergency department (ED) resuscitation. The percentage of patients receiving blood products based upon HD criteria ranged from 1.0% (HR) to 5.9% (SBP) to 38.1% (HR+SBP). In all, 74 Helicopter EMS (HEMS) transports met HD criteria for blood transfusion, of which, 28 patients received prehospital blood transfusion. Statistically significant total patient care time differences were noted for both the HR and the SBP cohorts, with HEMS having longer time intervals; no statistically significant difference in mean total patient care time was noted in the HR+SBP cohort.
ConclusionsIn this study population, HD parameters alone did not predict need for ED blood product administration. Despite longer transport times, only one-third of HEMS patients meeting HD criteria for blood administration received prehospital transfusion. While one-third of ground Advanced Life Support (ALS) transport patients manifesting HD compromise received blood products in the ED, this represented 0.2% of total trauma transports over the study period. Given complex logistical issues involved in prehospital blood product administration, opportunities for ground administration appear limited within the described system.
,Mix FM ,Zielinski MD ,Myers LA ,Berns KS ,Luke A ,Stubbs JR ,Zietlow SP ,Jenkins DH .Sztajnkrycer MD Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study . Prehosp Disaster Med.2018 ;33 (3 ):230 –236 .
Modeling 5 years of subglacial lake activity in the MacAyeal Ice Stream (Antarctica) catchment through assimilation of ICESat laser altimetry
- Sasha P. Carter, Helen A. Fricker, Donald D. Blankenship, Jesse V. Johnson, William H. Lipscomb, Stephen F. Price, Duncan A. Young
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- Journal of Glaciology / Volume 57 / Issue 206 / 2011
- Published online by Cambridge University Press:
- 08 September 2017, pp. 1098-1112
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Subglacial lakes beneath Antarctica’s fast-moving ice streams are known to undergo ∼1 km3 volume changes on annual timescales. Focusing on the MacAyeal Ice Stream (MacIS) lake system, we create a simple model for the response of subglacial water distribution to lake discharge events through assimilation of lake volume changes estimated from Ice, Cloud and land Elevation Satellite (ICESat) laser altimetry. We construct a steady-state water transport model in which known subglacial lakes are treated as either sinks or sources depending on the ICESat-derived filling or draining rates. The modeled volume change rates of five large subglacial lakes in the downstream portion of MacIS are shown to be consistent with observed filling rates if the dynamics of all upstream lakes are considered. However, the variable filling rate of the northernmost lake suggests the presence of an undetected lake of similar size upstream. Overall, we show that, for this fast-flowing ice stream, most subglacial lakes receive >90% of their water from distant distributed sources throughout the catchment, and we confirm that water is transported from regions of net basal melt to regions of net basal freezing. Our study provides a geophysically based means of validating subglacial water models in Antarctica and is a potential way to parameterize subglacial lake discharge events in large-scale ice-sheet models where adequate data are available.
Effect of Self-Expanding Carotid Stents on Plaque Thickness and Vessel Diameter
- Rafael Martínez-Pérez, Graeme Marchuk, Donald H. Lee, David M. Pelz, Stephen P. Lownie
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- Canadian Journal of Neurological Sciences / Volume 44 / Issue 5 / September 2017
- Published online by Cambridge University Press:
- 03 April 2017, pp. 498-502
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Background: In vitro models have suggested that stents affect atherosclerotic plaques symmetrically because of their outward radial forces. We evaluated the effects of stents on carotid plaque and the arterial wall using carotid ultrasound in carotid stenting patients to see whether these effects were borne out in vivo. Methods: From a carotid stent database, 30 consecutive patients were selected. All had carotid Doppler ultrasound performed pre- and poststenting. The diameters of the lumen at the level of stenotic plaque pre- and poststenting, the dorsal and ventral plaque thickness, and of the outer arterial wall diameter were measured. Plaque thickness was measured at the level of maximal stenosis. Nonparametric tests were used to determine whether the stent effect and luminal enlargement were based on wall remodeling or on total arterial expansion. Results: The patients were followed for an average of 22 months. Eighteen patients were male, with an average age of 70 years. A total of 87% of patients were symptomatic ipsilateral to the side of stenosis. Nine patients had angioplasty intraprocedurally. The luminal diameter increased poststenting in the region of severe stenosis. Plaque thickness, both ventrally and dorsally, decreased poststenting, with no significant difference between the ventral and dorsal plaque effects. The outer arterial wall diameters did not change. The measured lumen in the stent increased over time poststenting. Conclusions: Self-expanding nitinol stents alter the baseline ventral and dorsal plaque to a significant degree and do not significantly affect the native arterial wall and the overall arterial diameter.
Rattail Fescue (Vulpia Myuros) Control in Chemical-Fallow Cropping Systems
- Eric D. Jemmett, Donald C. Thill, Traci A. Rauch, Daniel A. Ball, Sandra M. Frost, Larry H. Bennett, Joseph P. Yenish, Rodney J. Rood
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- Weed Technology / Volume 22 / Issue 3 / September 2008
- Published online by Cambridge University Press:
- 20 January 2017, pp. 435-441
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Rattail fescue infestations are increasing in dryland conservation-tillage winter wheat cropping systems in the inland Pacific Northwest (PNW) region of Idaho, Oregon, and Washington. Rattail fescue typically is controlled with cultivation in conventional tillage farming systems. However, reduced soil disturbance has allowed infestations to increase significantly. The objectives of this research were to determine the effectiveness of glyphosate rates and application timings on control of rattail fescue during a chemical-fallow period in winter wheat cropping systems. Chemical-fallow field studies were conducted during two growing seasons at nine sites throughout the PNW. Glyphosate was applied early POST, late POST, or sequentially in early plus late POST timings. Additionally, paraquat + diuron was applied early and late POST alone or sequentially with glyphosate. Sequential application treatments (glyphosate followed by [fb] glyphosate, paraquat + diuron fb glyphosate, and glyphosate fb paraquat + diuron) controlled rattail fescue (∼ 94% in Idaho and Washington, ∼ 74% in Oregon) and reduced panicle number (∼ 85% in Idaho, ∼ 30% in Oregon and Washington) equivalent to or greater than one-time treatments. Rattail fescue control and panicle reduction generally increased with increasing rates of glyphosate within application timings. Paraquat + diuron usually provided similar control and reduced rattail fescue panicle number compared to glyphosate treatments applied at the same application timing. Although not completely effective, sequential applications of either glyphosate or paraquat + diuron, fb glyphosate will provide effective control during chemical fallow.
Baseline, Placebo, and Treatment: Efficient Estimation for Three-Group Experiments
- Alan S. Gerber, Donald P. Green, Edward H. Kaplan, Holger L. Kern
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- Political Analysis / Volume 18 / Issue 3 / Summer 2010
- Published online by Cambridge University Press:
- 04 January 2017, pp. 297-315
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Randomized experiments commonly compare subjects receiving a treatment to subjects receiving a placebo. An alternative design, frequently used in field experimentation, compares subjects assigned to an untreated baseline group to subjects assigned to a treatment group, adjusting statistically for the fact that some members of the treatment group may fail to receive the treatment. This article shows the potential advantages of a three-group design (baseline, placebo, and treatment). We present a maximum likelihood estimator of the treatment effect for this three-group design and illustrate its use with a field experiment that gauges the effect of prerecorded phone calls on voter turnout. The three-group design offers efficiency advantages over two-group designs while at the same time guarding against unanticipated placebo effects (which would undermine the placebo-treatment comparison) and unexpectedly low rates of compliance with the treatment assignment (which would undermine the baseline-treatment comparison).
Reconciling Individual and Aggregate Evidence Concerning Partisan Stability: Applying Time-Series Models to Panel Survey Data
- Donald P. Green, David H. Yoon
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- Political Analysis / Volume 10 / Issue 1 / Winter 2002
- Published online by Cambridge University Press:
- 04 January 2017, pp. 1-24
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Party identification has been studied extensively using both individual- and aggregate-level data. This paper attempts to formulate a statistical model that can account for the range of empirical generalizations that have emerged from aggregate time series and panel surveys. Using Monte Carlo simulation, we show that only certain types of data generation processes can account for these empirical regularities. Deciding which of the remaining types best explains the data means investigating the ways in which individual-level partisanship behaves over time. Partisanship at the aggregate-level tends to be highly autocorrelated, reequilibrating slowly in the wake of each perturbation. Working downward from the analysis of aggregate data, previous researchers argued that aggregate partisanship is fractionally integrated and contended that dynamics at the individual level are therefore heterogeneous. Using data from three panel surveys, we present the first direct assessment of individual-level dynamics. We also investigate the hypothesis that these dynamics vary among individuals, a claim that motivates much recent work on fractionally integrated time series. The model that best explains the observed characteristics of party identification is one in which individuals respond in similar ways to external shocks, reequilibrate rapidly thereafter, and seldom change their equilibrium level of partisan attachment.
The Epidemiology of Traumatic Spinal Cord Injury in Alberta, Canada
- Donna M. Dryden, L. Duncan Saunders, Brian H. Rowe, Laura A. May, Niko Yiannakoulias, Lawrence W. Svenson, Donald P. Schopflocher, Donald C. Voaklander
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- Canadian Journal of Neurological Sciences / Volume 30 / Issue 2 / May 2003
- Published online by Cambridge University Press:
- 16 December 2016, pp. 113-121
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Objectives:
To describe the incidence and pattern of traumatic spinal cord injury and cauda equina injury (SCI) in a geographically defined region of Canada.
Methods:The study period was April 1, 1997 to March 31, 2000. Data were gathered from three provincial sources: administrative data from the Alberta Ministry of Health and Wellness, records from the Alberta Trauma Registry, and death certificates from the Office of the Medical Examiner.
Results:From all three data sources, 450 cases of SCI were identified. Of these, 71 (15.8%) died prior to hospitalization. The annual incidence rate was 52.5/million population (95% CI: 47.7, 57.4). For those who survived to hospital admission, the incidence rate was 44.3/million/year (95% CI: 39.8, 48.7). The incidence rates for males were consistently higher than for females for all age groups. Motor vehicle collisions accounted for 56.4% of injuries, followed by falls (19.1%). The highest incidence of motor vehicle-related SCI occurred to those between 15 and 29 years (60/million/year). Fall-related injuries primarily occurred to those older than 60 years (45/million/year). Rural residents were 2.5 times as likely to be injured as urban residents.
Conclusion:Prevention strategies for SCI should target males of all ages, adolescents and young adults of both sexes, rural residents, motor vehicle collisions, and fall prevention for those older than 60 years.
Certification of standard reference material 1878b respirable α-quartz – CORRIGENDUM
- David R. Black, Marcus H. Mendenhall, Pamela S. Whitfield, Donald Windover, Albert Henins, James Filliben, James P. Cline
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- Powder Diffraction / Volume 31 / Issue 4 / December 2016
- Published online by Cambridge University Press:
- 28 October 2016, p. 304
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Certification of standard reference material 1878b respirable α-quartz
- David R. Black, Marcus H. Mendenhall, Pamela S. Whitfield, Donald Windover, Albert Henins, James Filliben, James P. Cline
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- Powder Diffraction / Volume 31 / Issue 3 / September 2016
- Published online by Cambridge University Press:
- 09 June 2016, pp. 211-215
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The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to address specific aspects of the performance of X-ray powder diffraction instruments. This report describes SRM 1878b, the third generation of this powder diffraction SRM. SRM 1878b is intended for use in the preparation of calibration standards for the quantitative analyses of α-quartz by X-ray powder diffraction in accordance to National Institute for Occupational Safety and Health Analytical Method 7500, or equivalent. A unit of SRM 1878b consists of approximately 5 g of α-quartz powder bottled in an argon atmosphere. It is certified with respect to crystalline phase purity, or amorphous phase content, and lattice parameter. Neutron powder diffraction, both time of flight and constant wavelength, was used to certify the phase purity using SRM 676a as an internal standard. A NIST-built diffractometer, incorporating many advanced design features was used for certification measurements for lattice parameters.
Certification of Standard Reference Material 1976B
- David R. Black, Donald Windover, Marcus H. Mendenhall, Albert Henins, James Filliben, James P. Cline
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- Powder Diffraction / Volume 30 / Issue 3 / September 2015
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- 12 August 2015, pp. 199-204
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The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to address specific aspects of the performance of X-ray powder diffraction instruments. This report describes SRM 1976b, the third generation of this powder diffraction SRM. SRM 1976b consists of a sintered alumina disc, approximately 25.6 mm in diameter by 2.2 mm in thickness, intended for use in the calibration of X-ray powder diffraction equipment with respect to line position and intensity as a function of 2θ-angle. The sintered form of the SRM eliminates the effect of sample loading procedures on intensity measurements. Certified data include the lattice parameters and relative peak intensity values from 13 lines in the 2θ region between 20° and 145° using CuKα radiation. A NIST-built diffractometer, incorporating many advanced and unique design features was used to make the certification measurements.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
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- 05 August 2015
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- 27 April 2015, pp ix-xxx
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Contributors
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- By Mowaffaq Almikhlafi, Osama Al-muslim, Robert Arntfield, Ian M Ball, Sue Berney, Mohit Bhutani, Clay A Block, Ken Blonde, Rudi Brits, Ron Butler, Lois Champion, Chris Clarke, Linda Denehy, Joseph Dreier, A Ebersohn, Shane W English, Ari Ercole, Darren H Freed, John Fuller, Julio P Zavala Georffino, RT Noel Gibney, Jeff Granton, Donald EG Griesdale, Arun K Gupta, Wael Haddara, Ahmed F Hegazy, Umjeet Singh Jolly, Philip M Jones, Ilya Kagan, Kala Kathirgamanathan, Harneet Kaur, John Kellett, Bhupesh Khadka, Biniam Kidane, Carlos Kidel, Anand Kumar, Alejandro Lazo-Langner, David Leasa, W Robert Leeper, Stephen Y Liang, Tania Ligori, Jaimie Manlucu, Janet Martin, Ian McConachie, Alan McGlennan, Lauralyn McIntyre, Tina Mele, MJ Naisbitt, Raj Nichani, Daniel H Ovakim, Neil Parry, Daniel Castro Pereira, Thomas Piraino, Brian Pollard, Valerie Schulz, Michael D Sharpe, Rohit K Singal, Pierre Singer, Mark Soth, Christian P Subbe, Jaffer Syed, Ravi Taneja, Tom Varughese, Jennifer Vergel Del Dios, Jessie R Welbourne, Christopher W White, Rebecca P Winsett, Titus C Yeung, G Bryan Young, Shelley R Zieroth
- Edited by John Fuller, University of Western Ontario, Jeff Granton, University of Western Ontario, Ian McConachie, University of Western Ontario
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- Handbook of ICU Therapy
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- 05 February 2015
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- 04 December 2014, pp vii-xii
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Intra-arterial Thrombolysis of Embolic Middle Cerebral Artery Using Collateral Pathways
- Max K. Kole, David M. Pelz, Donald H. Lee, Vivek Jain, J. David Spence, Stephen P. Lownie
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- Canadian Journal of Neurological Sciences / Volume 32 / Issue 2 / May 2005
- Published online by Cambridge University Press:
- 02 December 2014, pp. 257-260
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Background and purpose:
Cervical internal carotid artery (ICA) occlusion associated with middle cerebral artery (MCA) embolic occlusion requires prompt revascularization to prevent devastating stroke. With the advent of endovascular techniques for chemical and mechanical thrombolysis, the clinical outcome of patients with major arterial occlusions will improve. Finding the most expedient pathway to the site of end organ occlusion for thrombolysis is important.
Methods:We present two cases of acute stroke secondary to thrombotic occlusion of the cervical ICA associated with MCA embolic occlusion treated with intra-arterial thrombolysis via catheter navigation through the posterior communicating artery to the site of MCA arterial occlusion. No attempt was made to transverse the occluded ICA.
Results:Near complete restoration of flow was achieved in one patient and minimal vessel reopening was observed in the other patient. Both patients had good outcomes.
Conclusion:Intraarterial thrombolysis via Circle of Willis collaterals such as the posterior communicating artery for the treatment of acute thrombotic occlusion of the cervical internal carotid artery associated with embolic occlusion of the middle cerebral artery is a therapeutic option. This treatment option avoids the potential complications of navigating through an occluded proximal internal carotid artery and may expedite reopening of the MCA.
75 - EMS: the 8p11 myeloproliferative syndrome
- from Part 3.6 - Molecular pathology: lymphoma and leukemia
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- By Donald H. C. Macdonald, Department of Haematology, Imperial College, London, UK, Andreas Reiter, Medizinische Klinik, Univers¨atsmedizin Mannheim, Germany, Nicholas C. P. Cross, Wessex Regional Genetics Laboratory, University of Southampton, Salisbury District Hospital, Salisbury, UK
- Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
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- Molecular Oncology
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- 05 February 2015
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- 19 December 2013, pp 809-817
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Summary
Introduction
The “8p11 myeloproliferative syndrome” (EMS) is an extremely rare hematological malignancy characterized by disruption and constitutive activation of fibroblast growth-factor receptor type 1 (FGFR1; 1). The disease is also referred to as “stem-cell leukemia/lymphoma syndrome” (SCLL) or “myeloid and lymphoid neoplasms with FGFR1 abnormalities” (ICD-O code 9967/3; 2,3). Clinically, EMS is typically a biphenotypic disorder that may present as a myeloproliferative neoplasm, acute leukemia or lymphoblastic lymphoma, usually in conjunction with prominent eosinophilia. Although uncommon, EMS is of interest because of its stem-cell origin, marked genotype/phenotype correlations and diverse range of FGFR1 fusions, which all demonstrate a common pathogenic mechanism. Cell-line and animal studies have dissected the signaling pathways that are critical for transformation and may ultimately lead to molecularly targeted therapy.
Clinical features
Clinical and laboratory descriptions of more than 40 cases of EMS have been published and, although the clinical course is highly variable, some common features have emerged, as summarized in Table 75.1. The age range at onset is between 5 months and 84 years, with a median of 32 and a slight male to female predominance of 1.5:1. EMS may present as a myeloid and/or lymphoid malignancy; the myeloid presentation may be either a myeloproliferative neoplasm (MPN) or acute myeloid leukemia (AML), and the lymphoid presentation is typically either B-cell acute lymphoblastic leukemia (B-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
17 - Hepatocyte growth factor/Met signaling in cancer
- from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction
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- By Fabiola Cecchi, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda,MD, USA, Young H. Lee, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Donald P. Bottaro, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
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- Molecular Oncology
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- 05 February 2015
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- 19 December 2013, pp 204-217
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Summary
Introduction
Hepatocyte growth factor (HGF), also known as scatter factor (SF), was discovered on the basis of its ability to promote liver regeneration, and independently for its mitogenic activity on epithelial cells and its ability to induce cell scatter (1). HGF is secreted primarily by mesenchymal cells and drives cell motility, proliferation, survival, and morphogenesis by binding to the Met receptor tyrosine kinase (TK) present on a variety of target cell types (1–6). HGF/Met signaling is critical for normal development and adult homeostasis: deletion of either gene lethally disrupts embryogenesis (4,6) and up-regulation of HGF expression after kidney, liver, or heart injury protects against tissue damage and promotes repair and regeneration in adults (1,7–11). Under normal conditions, Met activation is tightly regulated by paracrine ligand delivery, ligand activation, and receptor internalization, dephosphorylation, and degradation (1). Despite this, HGF/Met signaling contributes to tumorigenesis, tumor angiogenesis, and metastasis in several prevalent cancers, a realization that has driven rapid growth in the development of experimental therapeutics targeting the pathway.
HGF and Met structure and function
The human HGF gene consists of 18 exons and 16 introns spanning 68 Mb on chromosome 7q21.11 (1). Five mRNA transcripts arise from alternative splicing: two encode full-length HGF forms and three encode truncated isoforms that bind Met, but differ in their biological activities (1). HGF protein is a plasminogen family member consisting of an amino-terminal heparin-binding domain (N), four kringle domains (K1–4) and a carboxyl-terminal serine-protease-like domain (Figure 17.1a). Unlike other plasminogen family members, HGF has no proteolytic activity (1). The HGF N and K1 domains contain the primary Met binding sites (12), and the protease-like domain contains an important secondary Met binding site (13). Proteolytic processing of the single-chain HGF precursor results in the active disulfide-linked heterodimer; the amino-terminal α-chain contains N and K1–4, and the β-chain contains the protease-like region (1).
Contributors
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- By Denis Barabé, Craig F. Barrett, Josef Bogner, Mark W. Chase, James I. Cohen, Natalie Cusimano, Jerrold I. Davis, Melvin R. Duvall, Carol A. Furness, Thomas J. Givnish, Rafaël Govaerts, Sean W. Graham, William J. D. Iles, F. Andrew Jones, Jim Leebens-Mack, Donald H. Les, Simon J. Mayo, Joel R. McNeal, Renato Mello-Silva, Jin Murata, C. David, L. Orme, Gitte Petersen, J. Chris Pires, Margarita V. Remizowa, Paula J. Rudall, Maria das Graças Sajo, Vincent Savolainen, Robert W. Scotland, Ole Seberg, Selena Y. Smith, Benjamin Sobkowiak, Dmitry D. Sokoloff, Dennis W. Stevenson, Norio Tanaka, Nicholas P. Tippery, Koichi Uehara, Paul Wilkin
- Edited by Paul Wilkin, Royal Botanic Gardens, Kew, Simon J. Mayo, Royal Botanic Gardens, Kew
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- Early Events in Monocot Evolution
- Published online:
- 05 June 2013
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- 30 May 2013, pp -
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