Using graphical probability analysis (Bayes Nets) to evaluate a conditional DNA inclusion

This paper discusses the analysis of cases in which the inclusion or exclusion of a particular suspect, as a possible contributor to a DNA mixture, depends on the value of a variable (the number of contributors) that cannot be determined with certainty. It offers alternative ways to deal with such cases, including sensitivity analysis and object-oriented Bayesian networks, that separate uncertainty about the inclusion of the suspect from uncertainty about other variables. The paper presents a case study in which the value of DNA evidence varies radically depending on the number of contributors to a DNA mixture: if there are two contributors, the suspect is excluded; if there are three or more, the suspect is included; but the number of contributors cannot be determined with certainty. It shows how an object-oriented Bayesian network can accommodate and integrate varying perspectives on the unknown variable and how it can reduce the potential for bias by directing attention to relevant considerations and distinguishing different sources of uncertainty. It also discusses the challenge of presenting such evidence to lay audiences.

3-T direct MR arthrography of the wrist: value of finger trap distraction to assess intrinsic ligament and triangular fibrocartilage complex tears.

PURPOSE: To determine the value of applying finger trap distraction during direct MR arthrography of the wrist to assess intrinsic ligament and triangular fibrocartilage complex (TFCC) tears. MATERIALS AND METHODS: Twenty consecutive patients were prospectively investigated by three-compartment wrist MR arthrography. Imaging was performed with 3-T scanners using a three-dimensional isotropic (0.4 mm) T1-weighted gradient-recalled echo sequence, with and without finger trap distraction (4 kg). In a blind and independent fashion, two musculoskeletal radiologists measured the width of the scapholunate (SL), lunotriquetral (LT) and ulna-TFC (UTFC) joint spaces. They evaluated the amount of contrast medium within these spaces using a four-point scale, and assessed SL, LT and TFCC tears, as well as the disruption of Gilula's carpal arcs. RESULTS: With finger trap distraction, both readers found a significant increase in width of the SL space (mean Δ = +0.1mm, p ≤ 0.040), and noticed more contrast medium therein (p ≤ 0.035). In contrast, the differences in width of the LT (mean Δ = +0.1 mm, p ≥ 0.057) and UTFC (mean Δ = 0mm, p ≥ 0.728) spaces, as well as the amount of contrast material within these spaces were not statistically significant (p = 0.607 and ≥ 0.157, respectively). Both readers detected more SL (Δ = +1, p = 0.157) and LT (Δ = +2, p = 0.223) tears, although statistical significance was not reached, and Gilula's carpal arcs were more frequently disrupted during finger trap distraction (Δ = +5, p = 0.025). CONCLUSION: The application of finger trap distraction during direct wrist MR arthrography may enhance both detection and characterisation of SL and LT ligament tears by widening the SL space and increasing the amount of contrast within the SL and LT joint spaces.

Temporal and spatial appearance of the membrane cytoskeleton and perineuronal nets in the rat neocortex.

Parvalbumin-immunoreactive interneurons are surrounded by perineuronal nets, containing molecules of the extracellular matrix (e.g. tenascin-R). Furthermore, they seem to have a special cytoskeleton composed of, among others, ankyrinR and beta Rspectrin. In the present developmental study we showed that the intracellular markers parvalbumin, ankyrinR and beta Rspectrin as well as Vicia Villosa agglutinin, an extracellular marker for perineuronal nets, appeared in the second postnatal week. In the third postnatal week, ankyrinR and beta R spectrin were present in the parvalbumin-positive interneurons. Tenascin-R appeared in a similar topographic distribution as the intracellular markers. The adult pattern was established upon the end of the fourth postnatal week. Our results indicate that cytoskeletal maturity maybe a prerequisite for the organization of perineuronal nets of extracellular matrix.

Eosinophilie sanguine: quel bilan, quel cheminement diagnostique [Peripheral blood eosinophilia: diagnostic value and further assessment].

Although not specific, an increased in peripheral blood eosinophils may contribute substantially to the diagnosis of numerous infectious, allergic and inflammatory diseases. The scope of this article is to detail pathologies associated with peripheral eosinophilia by order of frequency and to guide further investigations.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

AIM: To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS). MATERIALS AND METHODS: Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan-Meier were performed. RESULTS: Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p<0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR=5.6, p<0.001), positive SN (RR=5.0, p<0.001) and male sex (RR=2.9, p=0.001). The presence of a metastatic SN (RR=8.4, p<0.001), male sex (RR=6.1, p<0.001), Breslow thickness (RR=3.2, p=0.013) and ulceration (RR=2.6, p=0.015) were significantly associated with a poorer DSS. CONCLUSION: SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure

Diffusion-weighted MR imaging of the spine at 3-T: feasibility, optimization of b-value and utility to differentiate benign from pathological vertebral compression fractures

Purpose: To evaluate the feasibility, determine the optimal b-value, and assess the utility of 3-T diffusion-weighted MR imaging (DWI) of the spine in differentiating benign from pathologic vertebral compression fractures.Methods and Materials: Twenty patients with 38 vertebral compression fractures (24 benign, 14 pathologic) and 20 controls (total: 23 men, 17 women, mean age 56.2years) were included from December 2010 to May 2011 in this IRB-approved prospective study. MR imaging of the spine was performed on a 3-T unit with T1-w, fat-suppressed T2-w, gadolinium-enhanced fat-suppressed T1-w and zoomed-EPI (2D RF excitation pulse combined with reduced field-of-view single-shot echo-planar readout) diffusion-w (b-values: 0, 300, 500 and 700s/mm2) sequences. Two radiologists independently assessed zoomed-EPI image quality in random order using a 4-point scale: 1=excellent to 4=poor. They subsequently measured apparent diffusion coefficients (ADCs) in normal vertebral bodies and compression fractures, in consensus.Results: Lower b-values correlated with better image quality scores, with significant differences between b=300 (mean±SD=2.6±0.8), b=500 (3.0±0.7) and b=700 (3.6±0.6) (all p<0.001). Mean ADCs of normal vertebral bodies (n=162) were 0.23, 0.17 and 0.11×10-3mm2/s with b=300, 500 and 700s/mm2, respectively. In contrast, mean ADCs were 0.89, 0.70 and 0.59×10-3mm2/s for benign vertebral compression fractures and 0.79, 0.66 and 0.51×10-3mm2/s for pathologic fractures with b=300, 500 and 700s/mm2, respectively. No significant difference was found between ADCs of benign and pathologic fractures.Conclusion: 3-T DWI of the spine is feasible and lower b-values (300s/mm2) are recommended. However, our preliminary results show no advantage of DWI in differentiating benign from pathologic vertebral compression fractures.

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer.

BACKGROUND: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. METHODS: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. RESULTS: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. CONCLUSIONS: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.

The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox.

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).