All rights reserved. No part of this periodical may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permission for printing and for reprinting the material contained herein has been obtained by the publisher. A majority of soil studies in urban areas have focused on highly disturbed and human-constructed soils along streets and in highly developed areas (e.g.

SummaryWhen clustered multinomial responses are fit using the generalized logistic link, Morel (1989) introduced a small sample correction in the Taylor series based estimator of the covariance matrix of the parameter estimates. The correction reduces the bias of the Type I error rates in small samples and guarantees positive definiteness of the estimated variance-covariance matrix. It is well known that small sample bias in the use of the Delta method persists in any application of the Generalized Estimating Equations (GEE) methodology. In this article, we extend the correction originally suggested for the generalized logistic link, to other link functions and distributions, when parameters are estimated by GEE. In a Monte Carlo study with correlated data generated under different sampling schemes, the small sample correction has been shown to be effective in reducing the Type I error rates when the number of clusters is relatively small.

Background-The antiplatelet effect of aspirin is attributed to platelet cyclooxygenase-1 inhibition. Controversy exists on the prevalence of platelet resistance to aspirin in patients with coronary artery disease and effects of aspirin dose on inhibition. Our primary aim was to determine the degree of platelet aspirin responsiveness in patients, as measured by commonly used methods, and to study the relation of aspirin dose to platelet inhibition. Methods and Results-We prospectively studied the effect of aspirin dosing on platelet function in 125 stable outpatients with coronary artery disease randomized in a double-blind, double-crossover investigation (81, 162, and 325 mg/d for 4 weeks each over a 12-week period). At all doses of aspirin, platelet function was low as indicated by arachidonic acid (AA)-induced light transmittance aggregation, thrombelastography, and VerifyNow. At any 1 dose, resistance to aspirin was 0% to 6% in the overall group when AA was used as the agonist, whereas it was 1% to 27% by other methods [collagen and ADP-induced light transmittance aggregation, platelet function analyzer (PFA-100)]. Platelet response to aspirin as measured by collagen-induced light transmittance aggregation, ADP-induced light transmittance aggregation, PFA-100 (81 mg versus 162 mg, PՅ0.05), and urinary 11-dehydrothromboxane B 2 was dose-related (81 mg versus 325 mg, Pϭ0.003). No carryover effects were observed. Conclusions-The assessment of aspirin resistance is highly assay-dependent; aspirin is an effective blocker of AA-induced platelet function at all doses, whereas higher estimates of resistance were observed with methods that do not use AA as the stimulus. The observation of dose-dependent effects despite nearly complete inhibition of AA-induced aggregation suggests that aspirin may exert antiplatelet properties through non-cyclooxygenase-1 pathways and deserves further investigation. (Circulation. 2007;115:3156-3164.)

No abstract

We hypothesized that claw and foot pain could be objectively determined and have a strong effect on limb locomotion. Claw pain was measured using hoof testers equipped with a pressure gauge. Soft tissue pain was evaluated with an algometer. Pain was determined as the maximum pressure recorded at the time the limb was withdrawn following claw or soft tissue compression with the hoof tester or algometer. Locomotion scores and claw and soft tissue pain were determined on 263 Holstein cows from 2 commercial dairy farms. The frequency and the magnitude of pain had an effect on locomotion score in the ipsilateral limb for lateral, but not medial, claws. The magnitude of the lateral claw pain index for limbs with locomotion scores 1 to 5 was 0.95 +/- 0.01, 0.90 +/- 0.02, 0.67 +/- 0.04, 0.65 +/- 0.05, and 0.45 +/- 0.11, respectively. The magnitude of the medial claw pain index for limbs with locomotion scores 1 to 5 was 1.0 +/- 0.00, 0.99 +/- 0.01, 0.98 +/- 0.01, 1.0 +/- 0.00, and 1.0 +/- 0.00, respectively. The frequency of painful claws (n = 208) in limbs with locomotion scores 1, 2, and > or =3 was 0.529, 0.173, and 0.298, respectively. The frequency of painless claws (n = 318) in limbs with locomotion scores 1, 2, or > or =3 was 0.792, 0.088, and 0.120, respectively. The frequency of pain (27.1%) and total lesions (85.6%) was greater in lateral claws (n = 524) than that of pain (2.1%) and total lesions (14.4%) in medial claws (n = 524). Yet the magnitude of the pain index in sore claws was similar for medial (0.73 +/- 0.09) and lateral claws (0.64 +/- 0.02). The magnitude and frequency of claw pain in one hind limb was inconsistently and weakly affected by locomotion score or claw pain in the contralateral limb. The prevalence of unilateral (32.8%) and bilateral (23.3%) pain was similar and lower than the occurrence of bilaterally nonpainful claws (43.9%) in the study group. Painful claws (n = 78) occurred on sound limbs (n = 332) with a pain index (0.72 +/- 0.02) indicative of less pain than the pain index (0.61 +/- 0.02) of painful claws (n = 130) on lame limbs (n = 192). The results showed that lateral claw pain was related to ipsilateral limb locomotion score and subclinical pain was a relatively common occurrence. Objective measures of pain may provide a more reliable, continuous measure of clinical events used in modeling lameness.

appears concerned about the uniform inhibition of arachidonic acid-induced aggregation observed in the AspirinInduced Platelet Effect (ASPECT) trial. We would like to reassure Dr Klein that the compliance of the patients in ASPECT was meticulously recorded and, as reported in the manuscript, was overall 98%. Dr Klein should also be aware of the significance of results determined by double crossover studies such as the ASPECT study and the robust statistical analyses performed. 1 Why were we not surprised by the results of the ASPECT study? In a previous study of 223 patients undergoing stenting who were treated with long-term aspirin therapy, only 1 compliant patient was resistant as determined by cyclooxygenase-1 (COX-1)-specific assays and arachidonic acid-induced aggregation in plasma and in whole blood. Interestingly, all of the noncompliant patients (3%) had high arachidonic acid-induced aggregation, suggesting the presence of "resistance," but exhibited low arachidonic acid-induced aggregation after in-hospital treatment. 2 Therefore, the message of the study Tantry et al 2 and of the ASPECT trial is that aspirin responsiveness is very high when assessed by arachidonic acidbased assays in compliant patients. Moreover, the ASPECT study demonstrates the uniformity of this property irrespective of the aspirin dose. Therefore, the our data are not "overshot." Rather, they demonstrate an important physiological effect of aspirin, that is, near uniform and potent inhibition of COX-1. A recent study by others has demonstrated concordant findings. 3 We agree that noncompliance is an important issue with any pharmacological therapy. On the basis of our data, arachidonic acid-induced platelet aggregation is a good barometer of patient compliance with aspirin and probably other drugs, as patients who are noncompliant with aspirin may also be more likely to be noncompliant with their other prescribed medications.The second important message from the ASPECT study relates to the potential antiplatelet effects of aspirin mediated by non-COX-1 pathways assessed by stimulating platelets with agonists other than arachidonic acid. We are glad that Dr Klein has also raised this issue. This is indeed a novel idea with potential clinical implications, as recent studies have demonstrated the association of adverse clinical events with "aspirin resistance" measured by a method that is not solely dependent on COX-1 activity. 4 In our article, we state that "The observation of dose-related effects despite near-complete inhibition of arachidonic acid-induced aggregation suggests that aspirin may also exert antiplatelet effects through non-COX-1 pathways" (p 3163). Clearly, we are hypothesizing a novel antiplatelet effect of aspirin that should be the focus of future research, especially in diabetic patients where the dose-dependent antiplatelet effects of aspirin may be more pronounced. 5 It took at least 70 years to determine that aspirin inhibits platelet function by acetylating COX-1 and that aspirin can be used as an effective a...

SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

No abstract