Volumetric analysis of pelvic hematomas after blunt trauma using semi-automated seeded region growing segmentation: a method validation study.

OBJECTIVE: Manually segmented traumatic pelvic hematoma volumes are strongly predictive of active bleeding at conventional angiography, but the method is time intensive, limiting its clinical applicability. We compared volumetric analysis using semi-automated region growing segmentation to manual segmentation and diameter-based size estimates in patients with pelvic hematomas after blunt pelvic trauma. MATERIALS AND METHODS: A 14-patient cohort was selected in an anonymous randomized fashion from a dataset of patients with pelvic binders at MDCT, collected retrospectively as part of a HIPAA-compliant IRB-approved study from January 2008 to December 2013. To evaluate intermethod differences, one reader (R1) performed three volume measurements using the manual technique and three volume measurements using the semi-automated technique. To evaluate interobserver differences for semi-automated segmentation, a second reader (R2) performed three semi-automated measurements. One-way analysis of variance was used to compare differences in mean volumes. Time effort was also compared. Correlation between the two methods as well as two shorthand appraisals (greatest diameter, and the ABC/2 method for estimating ellipsoid volumes) was assessed with Spearman's rho (r). RESULTS: Intraobserver variability was lower for semi-automated compared to manual segmentation, with standard deviations ranging between ±5-32 mL and ±17-84 mL, respectively (p = 0.0003). There was no significant difference in mean volumes between the two readers' semi-automated measurements (p = 0.83); however, means were lower for the semi-automated compared with the manual technique (manual: mean and SD 309.6 ± 139 mL; R1 semi-auto: 229.6 ± 88.2 mL, p = 0.004; R2 semi-auto: 243.79 ± 99.7 mL, p = 0.021). Despite differences in means, the correlation between the two methods was very strong and highly significant (r = 0.91, p < 0.001). Correlations with diameter-based methods were only moderate and nonsignificant. Mean semi-automated segmentation time effort was 2 min and 6 s and 2 min and 35 s for R1 and R2, respectively, vs. 22 min and 8 s for manual segmentation. CONCLUSION: Semi-automated pelvic hematoma volumes correlate strongly with manually segmented volumes. Since semi-automated segmentation can be performed reliably and efficiently, volumetric analysis of traumatic pelvic hematomas is potentially valuable at the point-of-care.

Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions.

Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection.

Sample size determination for alternate periods of use study designs with binary responses.

In this article, we consider several study designs that arise in practice, which are variations of standard crossover designs. Often, they may result from modifications made to a standard crossover design due to practical considerations. Characteristic features of the studies we are concerned with are (a) treatments consist of external use of products with little or no possibility of carry over effects, and (b) the periods of use are dictated by the subjects or by some specific event, such as diaper leakage or menstrual flow. We consider a number of such study designs for estimating the difference in the efficacy of two treatments or test products. We provide brief descriptions of studies to motivate the study design, the underlying data structure, and computations of the variances of the usual unbiased estimators of the difference in efficacy, and the sample size formulas. The situations considered here cover a number of popular crossover designs. The objective of our work is to provide guidance to members of a wide audience on how to answer the sample size question for their own nonstandard situations. We conclude the article with a brief report on a simulation study we conducted to investigate the impact of estimation on the sample size determination and consequently on the actual power realized in an effort to promote the "best practice" of checking whether the recommended sample sizes indeed achieve the desired level of power.

Diversity in the magnitude of hind limb unloading occurs with similar forms of lameness in dairy cows.

The objective of the study was to evaluate the relationship of veterinary clinical assessments of lameness to probability estimates of lameness predicted from vertical kinetic measures. We hypothesized that algorithm-derived probability estimates of lameness would accurately reflect vertical measures in lame limbs even though vertical changes may not inevitably occur in all lameness. Kinetic data were collected from sound (n=179) and unilaterally lame (n=167) dairy cattle with a 1-dimensional, parallel force plate system that registered vertical ground reaction force signatures of all four limbs as cows freely exited the milking parlour. Locomotion was scored for each hind limb using a 1-5 locomotion score system (1=sound, 5=severely lame). Pain response in the interdigital space was quantified with an algometer and pain response in the claw was quantified with a hoof tester fitted with a pressure gage. Lesions were assigned severity scores (1=minimal pathology to 5=severe pathology). Lameness diminished the magnitude of peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses in the lame limbs of unilaterally lame cows. The only effect of lameness on the opposite sound limb was increased magnitude of stance times and vertical impulses in unilaterally lame cows. Symmetry measures of the peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses between the left and right hind limbs were also affected in unilateral lameness. Paradoxically, limbs with clinically similar lesion and locomotion scores and pain responses were associated with a broad range of load-transfer off the limb. Substantial unloading and changes in the vertical limb variables occurred in some lameness while minimal unloading and changes in vertical limb variables occurred in other lameness. Corresponding probability estimates of lameness accurately reflected changes in the vertical parameters of limbs and generated low probability estimates of lameness when minimal unloading occurred. Failure to transfer load off limbs with pain reactions, locomotion abnormalities and lesions explained much of the limited sensitivity in lameness detection with vertical limb variables.

Image-guided stereotactic radiosurgery for locally advanced pancreatic adenocarcinoma results of first 85 patients.

BACKGROUND: Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy. AIMS: The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center. METHODS: Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%. RESULTS: Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively. TOXICITY: A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%). CONCLUSIONS: 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.

Locomotion analysis of Sprague-Dawley rats before and after injecting 6-OHDA.

The hypothesis that changes in measured ground reaction forces and time parameters during locomotion can noninvasively detect Parkinsonism in unilateral 6-OH dopamine (6-OHDA) lesioned rats is tested. It was found that changes of seven locomotion parameters can be used to construct a logistic regression model with a detection sensitivity and specificity of over 90% as compared to non-lesioned rats. Comparisons between this model and other neurological and neuromuscular disorders are presented.

Gait analysis of locomotory impairment in rats before and after neuromuscular injury.

We used a gait analysis system (GAS) to measure the changes in locomotion parameters of adult Sprague-Dawley rats after neuromuscular injury, induced by repeated large-strain lengthening contractions of the dorsiflexors muscles. We developed a logistic regression model from test runs of control and permanently impaired (denervation of the dorsiflexor muscles) rats and used this model to predict the probabilities of locomotory impairment in rats injured by lengthening contractions. The data showed that GAS predicts the probability of locomotory impairment with very high reliability, with values close to 100% immediately after injury and close to 0% after several weeks of recovery from injury. The six transformed locomotion parameters most effective in the model were in three domains: frequency, force, and time. We conclude that application of the GAS instrument with our predictive model accurately identifies locomotory changes due to neuromuscular deficits. Use of this technology should be valuable for monitoring the progression of a neuromuscular disease and the effects of therapeutic interventions.

Measuring early pre-symptomatic changes in locomotion of SOD1-G93A rats--a rodent model of amyotrophic lateral sclerosis.

A locomotion analysis system for laboratory rats is presented. The system produces locomotion parameters (LPs) in 4 different domains: force, space, time and frequency. Video images of the walking rats are used to associate the system signals with individual limbs. Numerous LPs can be derived for every test run when the rat walks through the system on the way to sweets and a personal toy placed at the exit. This manuscript demonstrates that in order to differentiate SOD1-G93A mutant rat, a model of amyotrophic lateral sclerosis (ALS), from a Sprague Dawley (SD) control rat at a pre-symptomatic stage, one has only to use 8 key parameters. These 8 parameters are the bio-markers of ALS. The spline-based transformed values of these parameters are used as explanatory variables of a logistic regression model. This model predicts the probability that the examined rat belongs to the SOD1-G93A group. The model differentiates faultlessly between the SOD1 and control groups from the very first time the rats walked through the system at 51 days old. This system provides a new paradigm for ALS diagnosis, and it can have a significant impact on the development of new therapeutic procedures for ALS. The methodology presented in this manuscript can further address the development and validation of therapeutic procedures for other neurological diseases that affect locomotion.

Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.

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, P < or = 0.05), and urinary 11-dehydrothromboxane B2 was dose-related (81 mg versus 325 mg, P = 0.003). 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.