small bowel disease

Diagnostic imaging and in particular cross-sectional modalities (US, CT, and MR) have a critical and complementary role in diagnosis and management of small bowel diseases. Radiologists should be aware of advantages and disadvantages of each imaging test in order to choose the best option, considering the specific small bowel disease and the patient's characteristics (age, gender, clinical status). US is a powerful tool, especially in combination with oral (SICUS) and intravenous (CEUS) contrast agents. CT is the imaging modality of choice in the emergency setting (i.e., small bowel occlusion, ischemia, and, in some circumstances, bleeding). MR is the preferred imaging test in benign disorders, and in particular inflammatory bowel diseases (IBDs), because of multiparametric approach, evaluation of bowel motility, and lack of radiation exposure. A brief review of main findings in different pathological entities involving the small bowel is provided, in order to offer to radiologists the instruments for a correct diagnosis and for providing the clinicians with the necessary information for patient management

Using Pareto Fronts to Evaluate Polyp Detection Algorithms for CT Colonography

We evaluate and improve an existing curvature-based region growing algorithm for colonic polyp detection for our CT colonography (CTC) computer-aided detection (CAD) system by using Pareto fronts. The performance of a polyp detection algorithm involves two conflicting objectives, minimizing both false negative (FN) and false positive (FP) detection rates. This problem does not produce a single optimal solution but a set of solutions known as a Pareto front. Any solution in a Pareto front can only outperform other solutions in one of the two competing objectives. Using evolutionary algorithms to find the Pareto fronts for multi-objective optimization problems has been common practice for years. However, they are rarely investigated in any CTC CAD system because the computation cost is inherently expensive. To circumvent this problem, we have developed a parallel program implemented on a Linux cluster environment. A data set of 56 CTC colon surfaces with 87 proven positive detections of polyps sized 4 to 60 mm is used to evaluate an existing one-step, and derive a new two-step region growing algorithm. We use a popular algorithm, the Strength Pareto Evolutionary Algorithm (SPEA2), to find the Pareto fronts. The performance differences are evaluated using a statistical approach. The new algorithm outperforms the old one in 81.6% of the sampled Pareto fronts from 20 simulations. When operated at a suitable sensitivity level such as 90.8% (79/87) or 88.5% (77/87), the FP rate is decreased by 24.4% or 45.8% respectively

Hybrid Committee Classifier for a Computerized Colonic Polyp Detection System

We present a hybrid committee classifier for computer-aided detection (CAD) of colonic polyps in CT colonography (CTC). The classifier involved an ensemble of support vector machines (SVM) and neural networks (NN) for classification, a progressive search algorithm for selecting a set of features used by the SVMs and a floating search algorithm for selecting features used by the NNs. A total of 102 quantitative features were calculated for each polyp candidate found by a prototype CAD system. 3 features were selected for each of 7 SVM classifiers which were then combined to form a committee of SVMs classifier. Similarly, features (numbers varied from 10-20) were selected for 11 NN classifiers which were again combined to form a NN committee classifier. Finally, a hybrid committee classifier was defined by combining the outputs of both the SVM and NN committees. The method was tested on CTC scans (supine and prone views) of 29 patients, in terms of the partial area under a free response receiving operation characteristic (FROC) curve (AUC). Our results showed that the hybrid committee classifier performed the best for the prone scans and was comparable to other classifiers for the supine scans

Accuracy of CT Colonography for Detection of Large Adenomas and Cancers

Background Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined. Methods We recruited 2600 asymptomatic study participants, 50 years of age or older, at 15 study centers. CT colonographic images were acquired with the use of standard bowel preparation, stool and fluid tagging, mechanical insufflation, and multidetector-row CT scanners (with 16 or more rows). Radiologists trained in CT colonography reported all lesions measuring 5 mm or more in diameter. Optical colonoscopy and histologic review were performed according to established clinical protocols at each center and served as the reference standard. The primary end point was detection by CT colonography of histologically confirmed large adenomas and adenocarcinomas (10 mm in diameter or larger) that had been detected by colonoscopy; detection of smaller colorectal lesions (6 to 9 mm in diameter) was also evaluated. Results Complete data were available for 2531 participants (97%). For large adenomas and cancers, the mean (±SE) per-patient estimates of the sensitivity, specificity, positive and negative predictive values, and area under the receiver-operating-characteristic curve for CT colonography were 0.90±0.03, 0.86±0.02, 0.23±0.02, 0.99± Conclusions In this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer. (ClinicalTrials.gov number, NCT00084929; American College of Radiology Imaging Network [ACRIN] number, 6664.

ER Stress Induces Anabolic Resistance in Muscle Cells through PKB-Induced Blockade of mTORC1

Anabolic resistance is the inability to increase protein synthesis in response to an increase in amino acids following a meal. One potential mediator of anabolic resistance is endoplasmic reticulum (ER) stress. The purpose of the present study was to test whether ER stress impairs the response to growth factors and leucine in muscle cells

IL1B polymorphisms modulate cystic fibrosis lung disease

Rationale: Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection. Methods: We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort. All were homozygous for ΔF508, and categories of “severe” (cases) or “mild” (control subjects) lung disease were defined by the lowest or highest quartile of forced expired volume (FEV1) for age in the CF population. After adjustment for age and gender, genotypic data were tested for association with lung disease severity. Odds ratios (ORs) comparing severe versus mild CF were also calculated for each genotype (with the homozygote major allele as the reference group) for all 58 SNPs. From these analyses, nine SNPs with a moderate effect size, OR ≤ 0.5or > 1.5, were selected for further testing. To replicate the case-control study results, we genotyped the same nine SNPs in a second population of CF parent-offspring trios (recruited from Children’s Hospital Boston), in which the offspring had similar pulmonary phenotypes. For the trio analysis, both family-based and population-based associations were performed. Results: SNPs rs1143634 and rs1143639 in the IL1B gene demonstrated a consistent association with lung disease severity categories (P < 0.10) and longitudinal analysis of lung disease severity (P < 0.10) in CF in both the case-control and family-based studies. In females, there was a consistent association (false discovery rate adjusted joint P-value < 0.06 for both SNPs) in both the analysis of lung disease severity in the UNC/CWRU cohort and the family-based analysis of affection status. Conclusion: Our findings suggest that IL1β is a clinically relevant modulator of CF lung disease

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications