ACVIM consensus statement on the treatment of immune thrombocytopenia in dogs and cats

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats

Deep-tow magnetic anomaly study of the Pacific Jurassic Quiet Zone and implications for the geomagnetic polarity reversal timescale and geomagnetic field behavior

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): B07110, doi:10.1029/2007JB005527.The Jurassic Quiet Zone (JQZ) is a region of low-amplitude magnetic anomalies whose distinctive character may be related to geomagnetic field behavior. We collected deep-tow magnetic profiles in Pigafetta Basin (western Pacific) where previous deep-tow data partially covered the JQZ sequence. Our goals were to extend the survey through the JQZ, examine anomaly correlations, and refine a preliminary geomagnetic polarity timescale (GPTS) model. We collected a series of closely spaced profiles over anomaly M34 and Ocean Drilling Program Hole 801C to examine anomaly correlation in detail, one profile in between previous profiles, and two long profiles extending the survey deeper into the JQZ. Anomaly features can be readily correlated except in a region of low-amplitude, short-wavelength anomalies in the middle of the survey area (“low-amplitude zone” or LAZ). The small multiprofile surveys demonstrate anomaly linearity, implying that surrounding anomalies are also linear and likely result from crustal recording of geomagnetic field changes. We constructed a GPTS model assuming that most anomalies result from polarity reversals. The polarity timescale is similar to the polarity sequences from previous studies, but its global significance is uncertain because of problems correlating anomalies in the LAZ and the ambiguous nature of the small JQZ anomalies. Overall anomaly amplitude decreases with age into the LAZ and then increases again, implying low geomagnetic field strength, perhaps related to a rapidly reversing field. Other factors that may contribute to the LAZ are interference of anomalies over narrow, crustal polarity zones and poorly understood local tectonic complexities.This research was supported by the National Science Foundation grants OCE-0099161 and OCE-0099237. Tominaga was partly supported by funds from the Jane and R. Ken Williams ’45 Chair in Ocean Drilling Science, Education, and Technology

The Sr-Nd-Pb composition of Mesozoic Pacific oceanic crust (Site 1149 and 801, ODP Leg 185): Implications for alteration of ocean crust and the input into the Izu-Bonin-Mariana subduction system

We report Sr, Nd and Pb isotopic compositions of sediments and variably altered igneous rocks from ODP Site 801 (Marianas) and ODP Site 1149 (Izu-Bonin). These Sites provide the most complete drilled ocean crust sections located in front of the Mariana and Izu-Bonin trenches and characterize the unmodified isotopic input into these subduction zones. The subducted ocean crust belongs to the oldest (130–167 Ma) in situ Pacific Ocean crust and thus has end-member character with respect to alteration and sediment load. The lithostratigraphic division of sedimentary units at Site 1149 into clays, cherts, lower clays and carbonates with clay is reflected on isotope correlation diagrams. The Pb isotope data of the sediments show much greater variation than previously reported from this region. Particularly noteworthy are zeolite-bearing clays and clay bearing carbonates from the lower Units that have Pb isotopic compositions identical to the Izu Volcanic Front. The basaltic basement samples display variable 87Sr/86Sr ratios at near constant 143Nd/144Nd ratios, indicating mixing with seawater derived Sr. Most basaltic samples from Site 1149 and 801 exhibit highly variable 206Pb/204Pb (17.88–20.00) at near constant 207Pb/204Pb and 208Pb/204Pb ratios. Three samples from Site 801 display the most extreme 206Pb/204Pb (23.70–26.86) and 207Pb/204Pb (15.73–15.83) ratios ever measured in altered MORB reflecting an increase of 238U/204Pb ratios (μ), most likely through addition of seawater derived U. Initial Pb isotopes of most samples overlap with the age corrected field of the Pacific MORB source, thus the increase in μ took place shortly after formation of the crust in most samples. According to our new isotope data the radiogenic end-member of the Izu arc volcanic rocks could either represent Pb from the lower sediment column released from the slab by delayed dewatering or an integrated slab fluid in which 90–95% of the Pb comes from the basaltic crust and 5–10% of the Pb from the sediments. The Pb isotope systematics of the Mariana arc output suggest two component mixing. Both components appear to be input derived with the radiogenic component represented by average Site 801 sediment and the unradiogenic component generated by mixing of ∼80% unaltered crust with ∼20% highly altered crust

Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells

The nonclassical MHC class I molecule human histocompatibility leukocyte antigen (HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal–fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit maternal natural killer (NK) cells through interaction with particular NK cell receptors (KIRs). To investigate interactions of HLA-G, we constructed phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide. These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G tetramers did bind to peripheral blood monocytes, staining a CD16+CD14mid subset with greater intensity. On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However, staining in the presence of antibodies reactive with ILT receptors revealed that the interaction of HLA-G tetramers with blood monocytes was largely due to binding to ILT4. These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy

Revised Pacific M-anomaly geomagnetic polarity timescale

Author Posting. © The Authors, 2010. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 182 (2010): 203-232, doi:10.1111/j.1365-246X.2010.04619.x.The current M-anomaly geomagnetic polarity timescale (GPTS) is mainly based on the Hawaiian magnetic lineations in the Pacific Ocean. M-anomaly GPTS studies to date have relied on a small number of magnetic profiles, a situation that is not ideal because any one profile contains an uncertain amount of geologic 'noise' that perturbs the magnetic field signal. Compiling a polarity sequence from a larger array of magnetic profiles is desirable to provide greater consistency and repeatability. We present a new compilation of the M-anomaly GPTS constructed from polarity models derived from magnetic profiles crossing the three lineation sets (Hawaiian, Japanese and Phoenix) in the western Pacific. Polarity reversal boundary locations were estimated with a combination of inverse and forward modelling of the magnetic profiles. Separate GPTS were established for each of the three Pacific lineation sets, to allow examination of variability among the different lineation sets, and these were also combined to give a composite timescale. Owing to a paucity of reliable direct dates of the M-anomalies on ocean crust, the composite model was time calibrated with only two ages; one at each end of the sequence. These two dates are 125.0 Ma for the base of M0r and 155.7 Ma for the base of M26r. Relative polarity block widths from the three lineation sets are similar, indicating a consistent Pacific-wide spreading regime. The new GPTS model shows slightly different spacings of polarity blocks, as compared with previous GPTS, with less variation in block width. It appears that the greater polarity chron irregularity in older models is mostly an artifact of modelling a small number of magnetic profiles. The greater averaging of polarity chron boundaries in our model gives a GPTS that is statistically more robust than prior GPTS models and a superior foundation for Late Jurassic–Early Cretaceous geomagnetic and chronologic studies.This work was supported by the Jane & R. Ken Williams'45 Chair of Ocean Drilling Science and Technology

Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy

BACKGROUND: Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs. OBJECTIVES: To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics. ANIMALS: Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64). METHODS: Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 103 /μL, 2.0 × 103 /μL, and 2.5 × 103 /μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC <1.5 × 103 /μL but above the criteria for prophylactic antibiotics were evaluated. RESULTS: Chemotherapy was not administered in 7% of visits with an ANC cutoff of 1.5 × 103 /μL; chemotherapy would not have been administered in 10% and 16% of visits with an ANC cutoff of 2.0 × 103 /μL or 2.5 × 103 /μL, respectively. There was no association among the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75-1.5 × 103 /μL recovered spontaneously without medical intervention. CONCLUSION AND CLINICAL IMPORTANCE: The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 103 /μL, and the prechemotherapy ANC class 1.5-1.99 × 103 /μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 103 /μL in which to prescribe prophylactic antibiotics is indicated