Variability in CT lung-nodule quantification: Effects of dose reduction and reconstruction methods on density and texture based features.

PURPOSE: To investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules. METHODS: This study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature. RESULTS: The water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions. CONCLUSIONS: As expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.

Transplacental passage of clindamycin from mother to neonate.

OBJECTIVE: To evaluate maternal and neonatal cord blood levels at delivery in patients receiving 900 mg of clindamycin intravenous (IV) every 8 h. STUDY DESIGN: Prospective study consented every mother that entered labor with a positive group B streptococcal culture, a high-risk penicillin allergy, and sensitivity to clindamycin and erythromycin. Maternal and cord blood clindamycin levels were obtained at delivery. Time from last dose completion to delivery, number of doses administered and body mass index (BMI) were assessed. RESULTS: Twenty-three patients were consented. All maternal clindamycin values were therapeutic and 22 (96%) of the 23 cord blood samples were therapeutic. The mean maternal level was of 4.46 µg ml-1 (range of 0.7 to 8.4 µg ml-1). The mean cord blood level was 3.35 µg ml-1 (range of <0.5 to 6.4 µg ml-1). CONCLUSION: These data show that the current dosing recommendation of 900 mg of clindamycin IV every 8 h produces therapeutic maternal and cord blood levels.

Effects of fat and/or methionine hydroxy analog added to a molasses-urea-based supplement on ruminal and postruminal digestion and duodenal flow of nutrients in beef steers consuming low-quality lovegrass hay.

Five crossbred beef steers (initial BW = 338.6 ± 7.8 kg) fitted with ruminal and duodenal cannulas were used in a 5 × 5 Latin square design experiment to evaluate the effects of methionine hydroxy analog (MHA) and/or yellow grease (fat) added to a molasses-urea-based supplement on intake and characteristics of digestion. Steers were fed low-quality hay (long-stem lovegrass : 3.3% CP, 76.8% NDF; DM basis) ad libitum and supplemented with 0.91 kg/d (as fed) of 1 of 4 supplements in a 2 × 2 + 1 factorial arrangement of treatments. Supplemental treatments were 1) control (no supplement, NC); 2) molasses-urea liquid supplement (U); 3) U containing (as-fed basis) 1.65% MHA (UM); 4) U containing (as-fed basis) 12% fat (UF); and 5) U containing (as-fed basis) 1.65% MHA and 12% fat (UMF). Total and forage OM intake (kg/d and as % of BW) increased ( < 0.01) with molasses-urea, decreased ( ≤ 0.04) with MHA, and were not affected ( = 0.61) with fat supplementation. Total tract NDF digestibility increased ( = 0.01) with molasses-urea supplementation, and was less ( = 0.01) for fat than for nonfat supplementation. Total and microbial N flowing to the duodenum increased ( = 0.01) with molasses-urea supplementation. Although, total N flowing to duodenum was not affected ( = 0.27), microbial N decreased ( = 0.01), and nonammonia nonmicrobial N (NANMN) increased ( = 0.01) with fat supplementation. Extent of in situ OM and NDF digestibility at 96 h increased ( = 0.01) with molasses-urea supplementation, but were not affected ( ≥ 0.14) by either MHA or fat supplementation. Duodenal flow of total AA, essential AA, and nonessential AA increased ( ≤ 0.02) with molasses-urea supplementation. Total and nonessential serum AA concentration decreased ( < 0.01) with molasses-urea supplementation. Total ruminal VFA concentration increased ( = 0.01) with molasses-urea supplementation, and was not affected ( ≥ 0.14) by MHA or fat supplementation. Fat can be used in molasses-urea liquid supplements for cattle consuming low-quality forage to increase energy intake without negatively affecting forage intake or characteristics of digestion. However, adding MHA did not further improve the response to urea supplementation of cattle consuming low-quality forage. Conversely, the inclusion of MHA on urea supplement decreased forage intake.

Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography.

PURPOSE: To investigate the efficacy of a new family of measurements made on individual pulmonary cysts extracted from computed tomography (CT) for assessing the severity of lymphangioleiomyomatosis (LAM). METHODS: CT images were analyzed using thresholding to identify a cystic region of interest from chest CT of LAM patients. Individual cysts were then extracted from the cystic region by the watershed algorithm, which separates individual cysts based on subtle edges within the cystic regions. A family of measurements were then computed, which quantify the amount, distribution, and boundary appearance of the cysts. Sequential floating feature selection was used to select a small subset of features for quantification of the severity of LAM. Adjusted R(2) from multiple linear regression and R(2) from linear regression against measurements from spirometry were used to compare the performance of our proposed measurements with currently used density based CT measurements in the literature, namely, the relative area measure and the D measure. RESULTS: Volumetric CT data, performed at total lung capacity and residual volume, from a total of 49 subjects enrolled in the MILES trial were used in our study. Our proposed measures had adjusted R(2) ranging from 0.42 to 0.59 when regressing against the spirometry measures, with p < 0.05. For previously used density based CT measurements in the literature, the best R(2) was 0.46 (for only one instance), with the majority being lower than 0.3 or p > 0.05. CONCLUSIONS: The proposed family of CT-based cyst measurements have better correlation with spirometric measures than previously used density based CT measurements. They show potential as a sensitive tool for quantitatively assessing the severity of LAM.

Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial.

OBJECTIVE: Compare duration of treatment of neonatal abstinence syndrome between methadone and morphine. STUDY DESIGN: A prospective, double-masked, randomized trial at a single site. Randomization of methadone or morphine was stratified for maternal treatment with methadone or buprenorphine. Inclusion criteria were (i) maternal treatment with prescribed methadone or buprenorphine, (ii) withdrawal treatment criteria, (iii) adjusted gestational age ⩾35(0/7) weeks and (iv) medically stable. Primary outcome was length of opioid treatment. RESULT: From January 2011 through October 2012, 78 infants were eligible for the study: 41 methadone-exposed and 37 buprenorphine-exposed. Consent was obtained from 31 mothers, 13/41 (32%) methadone-treated and 18/37 (49%) buprenorphine-treated. Length of opioid treatment was significantly shorter for methadone than morphine treatment, median 14 versus 21 days (P=0.008). CONCLUSION: Methadone had a shorter length of neonatal withdrawal treatment compared with morphine. Owing to the smaller sample size and single site, a larger randomized study is needed.

Orbitofrontal cortex volume and brain reward response in obesity.

BACKGROUND/OBJECTIVES: What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently, brain orbitofrontal cortex (OFC) volume has been implicated in dysregulated eating but little is known how brain structure relates to function. SUBJECTS/METHODS: We examined obese (n=18, age=28.7±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter (WM) integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function. RESULTS: Obese individuals displayed lower gray and associated white matter volumes (P<0.05 family-wise error (FWE)- small volume corrected) compared with controls in the orbitofrontal cortex, striatum and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals. CONCLUSIONS: This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity (OB) may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.

Effects of wet corn distillers grains with solubles on visceral organ mass, trace mineral status, and polioencephalomalacia biomarkers of individually-fed cattle.

Twenty-four steers (initial BW = 385 ± 1.1 kg) were blocked by BW and randomly assigned to 3 dietary treatments (0, 30, or 60% wet distillers grains with solubles [WDGS]; DM basis) and were fed individually to determine the effect of WDGS on live growth and carcass performance, visceral organ mass, trace mineral status, and polioencephalomalacia biomarkers. Steers were slaughtered at 125, 150, 164, and 192 d (2 blocks/slaughter date) when external fat depth was approximately 1.3 cm based on visual appraisal. Steers fed 30% WDGS had greater DMI than those fed 0 or 60% WDGS (P < 0.05), and steers fed 60% WDGS had the lowest carcass-adjusted ADG (P < 0.09) of the 3 treatments. Nonetheless, WDGS concentration did not alter feed efficiency (P > 0.41) on either live or carcass-adjusted basis. Steers fed 30% WDGS had greater liver S and Mn concentrations (DM basis) and lower liver Fe concentrations than control steers (P < 0.10; initial values used as a covariate), and feeding 60% WDGS decreased liver Cu and increased liver Fe (P < 0.10) compared with feeding 30% WDGS. Cytochrome c oxidase (COX) activity in brain tissue tended to be decreased with 60 vs. 30% WDGS (P = 0.12), and COX activity decreased linearly (P = 0.06) in lung tissue as dietary WDGS concentration increased. Likewise, gut fill linearly increased (P = 0.01) with increasing WDGS concentration. Feeding 30% WDGS increased fractional mass (g/kg of empty BW) of the small intestine (P < 0.10) compared with controls, whereas 60% WDGS increased fractional kidney mass (P < 0.10) compared with 30% WDGS. Overall, results suggest that gut fill, Cu status, and COX activity seem to be compromised by WDGS when fed at 60% of diet DM in diets based on steam-flaked corn, which suggests a greater susceptibility to polioencephalomalacia.

Effects of a dietary sweetener on growth performance and health of stressed beef calves and on diet digestibility and plasma and urinary metabolite concentrations of healthy calves.

Two experiments were conducted to explore the effects of a sodium saccharin-based dietary sweetener (Sucram) on growth performance, health, and physiological responses of feedlot steers. In Exp. 1, 173 newly-received male calves purchased from auction barns were fed 0, 100, 200, or 300 g of Sucram/t of DM over 56 d. Overall, ADG and G:F (P > 0.10) were not different among treatments, but steers receiving 200 g Sucram/t displayed numerically greater ADG (23%). In addition, DMI was 17% greater for steers receiving 200 g of Sucram/t compared to steers fed the control diet (cubic effect, P = 0.09). The morbidity rate for respiratory disease did not differ (P > 0.50) among treatments. In Exp. 2, 15 steers (initial BW = 261 ± 28 kg) were used to evaluate the effects of Sucram on apparent total tract digestibility, plasma metabolite concentrations, and urine monoamine metabolite concentrations. Treatments consisted of ad libitum access to a 60% concentrate diet (Control), ad libitum access to Control + 200 g of Sucram/t of DM (Adlib), and Control + 200 g of Sucram/t of DM with feed intake paired to the Control (Paired). By design, steer DMI during the metabolism period did not differ (P = 0.34) between Paired and Control, but DMI tended (P = 0.14) to be 8.2% greater for Adlib than for Control. Treatments did not alter (P > 0.17) apparent total tract nutrient digestibility. Postprandial plasma citrulline concentration was lower (P = 0.03) for Adlib than for Control and tended to be lower (P = 0.13) for Paired than for Control. Plasma homocysteine concentration was reduced (P < 0.03) by feeding Sucram. Urinary concentrations of ethylmalonic acid, vanillymandelic acid, and 5-hydroxyindolacetic acid were greater (P < 0.06) for Adlib than for Control; Paired steers had a greater (P = 0.02) urine vanillymandelic acid concentration than Control steers and tended (P < 0.12) to have a greater urinary concentration of ethylmalonic and 5-hydroxyindolacetic acid than Control steers. Serum insulin was greater for Adlib than for Control steers (P = 0.04) and tended to be greater for Paired than for Control steers (P = 0.14), but serum prolactin area did not differ (P > 0.22) among treatments. Supplementation with Sucram may increase feed intake by newly-received, stressed feedlot calves. Saccharin supplementation reduced plasma homocysteine and increased urinary excretion of vanillymandelic acid, suggesting an improved activity of the dopamine reward system.

Effects of glycerin on receiving performance and health status of beef steers and nutrient digestibility and rumen fermentation characteristics of growing steers.

One experiment was conducted to evaluate the influence of glycerin (GLY) on animal performance and health when used as a partial replacement for roughage in receiving diets. The second experiment was conducted using ruminally and duodenally cannulated steers in a 4 × 4 Latin square to determine the site of nutrient digestion and ruminal fermentation characteristics when GLY replaced roughage at 0%, 2.5%, 5%, and 10% of diet DM. In Exp. 1, steers (initial BW = 245 ± 2.3 kg) were fed treatment diets over a 42-d period that consisted of a control diet based on steam-flaked corn with GLY inclusion in replacement of dietary roughage at 0%, 5%, and 10% of diet DM. A linear reduction in DMI was observed as GLY increased (P = 0.01). Glycerin incorporation tended to improve G:F in a linear manner (P = 0.07); efficiency was improved 5.4% and 4.7% at 5% and 10% GLY. The number of animals receiving treatment for bovine respiratory disease did not differ among treatments. Furthermore, there were no differences among treatments for mortality or the frequency of steers that were seropositive for serum antibody titers to infectious bovine rhinotracheitis on d 28. In Exp. 2, apparent OM and apparent and true starch digestibility increased linearly (P < 0.05) as GLY concentration increased, whereas true OM digestibility responded in a quadratic (P < 0.01) manner. Bacterial OM and bacterial starch flow responded quadratically (P ≤ 0.02), and flow increased from 0% to 5% GLY inclusion and decreased thereafter. Feed OM flow responded quadratically (P ≤ 0.05), where it decreased from 0% to 2.5% GLY and increased from 2.5% to 10% GLY inclusion. Feed starch (P = 0.02) and total starch (P = 0.02) flow from the duodenum decreased linearly as the concentration of GLY increased in the diet. Bacterial N flow to the duodenum responded quadratically (P < 0.01); it increased with increasing GLY in the diet up to 5% and then decreased from 5% to 10%. The acetate to propionate (A:P) ratio in the ruminal fluid decreased (P < 0.05) as the concentration of GLY in the diet increased, which could have implications on improved G:F. The decrease in the A:P ratio as GLY increased in the diet, coupled with the linear decrease in DMI and improvement in G:F with GLY addition up to 5% of DM in place of roughage, implies that GLY is a viable dietary ingredient in growing and receiving diets.

Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations.

OBJECTIVE: This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. METHODS: In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. RESULTS: NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. CONCLUSIONS: Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

MLK4ß functions as a negative regulator of MAPK signaling and cell invasion.

Mixed lineage kinase (MLK) 4, or MLK4, is a member of the MLK family of mitogen-activated protein kinase kinase kinases (MAP3Ks). Typically, MAP3Ks function to activate the mitogen-activated protein kinase (MAPK)-signaling pathways and regulate different cellular responses. However, here we report that MLK4ß, unlike the other MLKs, negatively regulates the activities of the MAPKs, p38, c-Jun N-terminal kinase and extracellular signal-regulated kinase, and the MAP2Ks, MEK3 and 6. Our results show that MLK4ß inhibits sorbitol- and tumor necrosis factor-induced activation of p38. Furthermore, MLK4ß interacts with another MLK family member, MLK3, in HCT116 cells. Exogenous expression of MLK4ß inhibits activation of MLK3 and also blocks matrix metalloproteinase-9 gelatinase activity and invasion in SKOV3 ovarian cancer cells. Collectively, our data establish MLK4ß as a novel suppressor of MLK3 activation, MAPK signaling and cell invasion.

Surviving starvation: essential role of the ghrelin-growth hormone axis.

After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Mice were fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23 h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60 mg/dL. In Goat(-/-) mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20 mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma.

BACKGROUND AND PURPOSE: Currently it is difficult to predict tumor response to anti-angiogenic therapy in individual patients. Our aim was to determine if ADC histogram analysis can stratify progression-free and overall survival in patients with newly diagnosed GBM treated "up-front" (ie, before tumor recurrence) with bevacizumab. MATERIALS AND METHODS: Up-front bevacizumab-treated and control patients (n = 59 and 62, respectively) with newly diagnosed GBM were analyzed by using an ADC histogram approach based on enhancing tumor. Progression-free and overall survival was determined by using Cox proportional HRs and the Kaplan-Meier method with logrank and Wilcoxon tests. RESULTS: For up-front bevacizumab-treated patients, lower ADC(L) was associated with significantly longer progression-free survival (median, 459 days for ADC(L) < 1200 versus 315 days for ADC(L) ≥ 1200 10(-6)mm(2)/s; P = .008, logrank test) and trended with longer overall survival (581 versus 429 days, P = .055). ADC values did not stratify progression-free or overall survival for patients in the control group (P = .92 and P = .22, respectively). Tumors with MGMT promoter methylation had lower ADC(L) values than unmethylated tumors (mean, 1071 versus 1183 10(-6)mm(2)/s; P = .01, 2-group t test). CONCLUSIONS: Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADC(L) tumors.

Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: Memory impairment is common in patients with systemic lupus erythematosus (SLE). This study examined hippocampal volumes and neurometabolic alterations in relation to memory function in SLE patients without a history of neuropsychiatric syndromes (nonNPSLE). METHODS: Subjects included 81 nonNPSLE patients and 34 healthy controls. Volumetric magnetic resonance imaging and magnetic resonance spectroscopy of the right and left hippocampal areas (RH, LH) were performed. Verbal and visual memory tests were administered and a memory impairment index (MII) was derived from standardized tests. RESULTS: Higher memory impairment (MII) was correlated with lower RH glutamate + glutamine/creatine (p = 0.009) and lower RH N-acetylaspartic acid/creatine (p = 0.012) in nonNPSLE patients. A trend for a negative correlation between RH and LH volumes and MII was evident for absolute hippocampal volumes. Lower RH glutamate + glutamine/creatine was also correlated with worse performance in a mean visual memory index (p = 0.017). CONCLUSIONS: An association between reduced memory and lower N-acetylaspartic acid/creatine in the RH suggests neuronal damage in nonNPSLE patients with very mild and early disease. Alterations in glutamate + glutamine/creatine further indicate early metabolic changes in nonNPSLE are related to memory impairment, a finding that might suggest that memory impairment relates to presynaptic glutamatergic dysfunction in the hippocampus.

Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab.

OBJECTIVE: We evaluated patterns of tumor progression in patients with recurrent glioblastoma who were treated with bevacizumab (BEV) alone or in combination with irinotecan (CPT-11) while participating in the BRAIN study. METHODS: An independent neuroradiologist reviewed MRI scans at baseline and progression in patients who received BEV (n = 85) or BEV+CPT-11 (n = 82) while on BRAIN. Tumor patterns were scored as local, distant, diffuse, or multifocal. Median progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Hazard ratios for PFS and OS were estimated using a Cox regression model. RESULTS: Twenty-eight percent of patients who participated in BRAIN had nonlocal disease at baseline (72% local disease). Sixty-seven (79%) patients treated with single-agent BEV and 57 (70%) patients treated with BEV+CPT-11 experienced disease progression while on BRAIN. Most patients in each treatment group did not have a change in the radiographic pattern of their tumor (i.e., "no shift") at the time of progression. The proportion of BEV patients with no shift (82%) was greater than that of BEV+CPT-11 patients (53%, χ(2) p = 0.0004), and a greater proportion of BEV+CPT-11 patients (39%) compared with BEV patients (16%) experienced local-to-diffuse tumor pattern at progression (χ(2) p = 0.002). Patients treated with BEV or BEV+CPT-11 who had local-to-local or local-to-diffuse progression patterns had similar efficacy outcomes, including objective response, PFS, and OS. CONCLUSIONS: Most patients treated with BEV or BEV+CPT-11 on BRAIN did not experience a change from baseline in radiographic characteristics of disease at the time of progression.

A computer-aided diagnosis system for quantitative scoring of extent of lung fibrosis in scleroderma patients.

OBJECTIVES: To evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CAD) system that classifies CT pixels with the visual semi-quantitative pulmonary fibrosis score in patients with scleroderma-related interstitial lung disease (SSc-ILD). METHODS: High-resolution, thin-section CT images were obtained and analysed on 129 subjects with SSc-ILD (36 men, 93 women; mean age 48.8±12.1 years) who underwent baseline CT in the prone position at full inspiration. The CAD system segmented each lung of each patient into 3 zones. A quantitative lung fibrosis (QLF) score was established via 5 steps: 1) images were denoised; 2) images were grid sampled; 3) the characteristics of grid intensities were converted into texture features; 4) texture features classified pixels as fibrotic or non-fibrotic, with fibrosis defined by a reticular pattern with architectural distortion; and 5) fibrotic pixels were reported as percentages. Quantitative scores were obtained from 709 zones with complete data and then compared with ordinal scores from two independent expert radiologists. ROC curve analyses were used to measure performance. RESULTS: When the two radiologists agreed that fibrosis affected more than 1% or 25% of a zone or zones, the areas under the ROC curves for QLF score were 0.86 and 0.96, respectively. CONCLUSIONS: Our technique exhibited good accuracy for detecting fibrosis at a threshold of both 1% (i.e. presence or absence of pulmonary fibrosis) and a clinically meaningful threshold of 25% extent of fibrosis in patients with SSc-ILD.

Technical note: Analysis of ordinal outcomes from carcass data in beef cattle research.

Beef cattle research commonly uses Yield grade (YG) and Quality grade (QG) as outcomes in nutrition and health experiments. These outcomes, as commonly reported and analyzed, are ordinal variables with an assumed rank derived from an underlying latent variable that may or may not be available for analysis. The objective of this study was to employ mixed-effects ordinal regression and approaches previously reported in animal science and veterinary literature such as contingency table analysis, mixed-effects linear regression, and mixed-effects logistic regression for the analysis of YG and QG data and to compare results with respect to statistical significance and estimated statistical power. Five randomized complete block design experiments were used for initial evaluation. Simulated data sets were used for evaluation of relative differences in statistical power. Scenarios were observed where all of the methods differed in estimate of effect and statistical significance. Power to detect an association was similar between studies under the scenario evaluated. Ordinal regression approaches provide an estimate of effect that can be used in subsequent prediction of performance, which is an advantage over contingency table approaches that only report statistical significance. Further, ordinal models do not require modification of the outcome variable as in logistic regression or assumptions regarding YG or QG distribution in linear regression, which are often not met. Researchers faced with analysis of YG and QG data should consider the use of ordinal regression, particularly with recent advances in statistical software packages capable of implementing this method for data within hierarchical models.

Perceptions of undergraduate students not participating in HIV/AIDS prevention activities in Botswana.

BACKGROUND: Botswana is one of the countries hardest hit by HIV/AIDS. Prevalence rates of 22.8% and 38.6% have been reported for age groups 15-19 and 20-24 years respectively. The government has solicited a concerted effort of all individuals and agencies in both the public and private sector in the fight against HIV/AIDS. PURPOSE: This report is part of the findings of a study conducted at a university to evaluate students' perceptions of the effectiveness of two HIV/AIDS initiatives put in place and aimed at changing the students' knowledge, attitudes and behaviour. METHODS: The study utilized the Rapid Assessment Process (RAP). Four teams interviewed: students who had taken the course; students who had used the centre; students who had taken the course and used the centre; and students who have neither taken the course nor used the centre. Initial steps in data analysis involved coding and theme derivation. Findings reported here were from participants who neither participated in the course nor used the centre. FINDINGS: Participants reported the following problems, which were hindering the success of the programmes: problems in the ABC message; permissive campus environment; lack of entertainment; and students' perceptions about HIV/AIDS and their own vulnerability. Participants came up with suggestions for improving the initiatives. The authors discuss implications of the study findings for the university's initiatives.