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Background: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. Methods: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. Results: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. Conclusion: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA. [ABSTRACT FROM AUTHOR]

The electrocardiogram (ECG) can capture obesity-related cardiac changes. Artificial intelligence-enhanced ECG (AI-ECG) can identify subclinical disease. We trained an AI-ECG model to predict body mass index (BMI) from the ECG alone. Developed from 512,950 12-lead ECGs from the Beth Israel Deaconess Medical Center (BIDMC), a secondary care cohort, and validated on UK Biobank (UKB) (n = 42,386), the model achieved a Pearson correlation coefficient (r) of 0.65 and 0.62, and an R2 of 0.43 and 0.39 in the BIDMC cohort and UK Biobank, respectively for AI-ECG BMI vs. measured BMI. We found delta-BMI, the difference between measured BMI and AI-ECG-predicted BMI (AI-ECG-BMI), to be a biomarker of cardiometabolic health. The top tertile of delta-BMI showed increased risk of future cardiometabolic disease (BIDMC: HR 1.15, p < 0.001; UKB: HR 1.58, p < 0.001) and diabetes mellitus (BIDMC: HR 1.25, p < 0.001; UKB: HR 2.28, p < 0.001) after adjusting for covariates including measured BMI. Significant enhancements in model fit, reclassification and improvements in discriminatory power were observed with the inclusion of delta-BMI in both cohorts. Phenotypic profiling highlighted associations between delta-BMI and cardiometabolic diseases, anthropometric measures of truncal obesity, and pericardial fat mass. Metabolic and proteomic profiling associates delta-BMI positively with valine, lipids in small HDL, syntaxin-3, and carnosine dipeptidase 1, and inversely with glutamine, glycine, colipase, and adiponectin. A genome-wide association study revealed associations with regulators of cardiovascular/metabolic traits, including SCN10A, SCN5A, EXOG and RXRG. In summary, our AI-ECG-BMI model accurately predicts BMI and introduces delta-BMI as a non-invasive biomarker for cardiometabolic risk stratification. [ABSTRACT FROM AUTHOR]

Maternal autoantibody-related complete heart block in the fetus is considered irreversible. During prenatal care for a 25-year-old nulliparous Hispanic woman with newly diagnosed nephrotic-range proteinuria and positive anti-nuclear antigen antibody, complete fetal heart block with a ventricular rate of 60 beats per minute was detected on a fetal echocardiogram at 28-week gestation. A small pericardial effusion and ascites were noted consistent with fetal hydrops. Dexamethasone and hydroxychloroquine were initiated. Fetal rhythm improved to Mobitz type 1 second-degree heart block, with a ventricular rate of 91 beats per minute. The fetus was born prematurely at 34-week gestation with second-degree heart block which improved to first-degree heart block prior to hospital discharge. First-degree heart block persisted at 2 years of age with a P-R interval of 185 ms. Transplacental treatment with dexamethasone and hydroxychloroquine was associated with sustained reversal of complete heart block to sinus rhythm. [ABSTRACT FROM AUTHOR]

Transport infrastructure systems are very complex and expensive. Projects to procure such systems are costly, long and complex to manage. The procurement context usually includes many collaborating organizations but often with different concerns and priorities, and many interactions to other parties. This makes the procurement very complex and entangled. DoDAF, MoDAF and TRAK are three architecture frameworks (AF) that model the whole enterprise/system life cycle that includes system procurement. They are expressed as metamodels. In this paper, we analyse various procurements strategies and identify the concerns that AFs should address. The TRAK AF is then applied to a Rail procurement case study in collaboration with Transport for New South Wales (NSW) in Australia to assess its effectiveness in meeting the procurement needs. In all stages of the study, TRAK is mapped and compared to DoDAF and MoDAF to examine whether DoDAF or MoDAF can cover the inadequacies of TRAK. This paper shows that there is a considerable number of procurement needs which are overlooked by these architecture frameworks. It proposes a metamodel driven expansion to these frameworks to improve their completeness and expressiveness. [ABSTRACT FROM AUTHOR]

While much excitement has attended the discovery and study of circular RNAs, a new study in Cell Reports suggests that most mammalian circRNAs are not only functionless, but in fact costly. Comparison across three species is also consistent with the influential but rarely tested Drift-Barrier Hypothesis of molecular complexity. According to this hypothesis, nonessential genomic elements are slightly deleterious elements that fix by genetic drift and, thus, are generally more abundant in species with small effective population sizes. I discuss the implications of these new results for the Drift-Barrier hypothesis. In particular, I note the distinction between two classes of genomic elements, based on whether they are created by 'standard' small-scale mutations (basepair substitutions, indels, etc.) or larger, more idiosyncratic mutations (segmental duplications, transposable element propagation, etc.) I suggest that the Drift-Barrier Hypothesis is likely to apply to the former class, but perhaps not the latter class. [ABSTRACT FROM AUTHOR]

Shakedown analysis is an attractive method for determining the capacity of geostructures to sustain repeated loads involving a large number of cycles, e.g. rolling and sliding train wheel loads. Its main advantage is that it comes at a significantly reduced computational cost, compared to standard time-domain analyses. An essential component of shakedown analysis is the derivation of closed-form solutions to compute stresses due to the external repeated loads, a task that is not always feasible for complex problems as the ballasted rail track discussed herein. To tackle this, we present in this paper the use of finite element tools to obtain a quasi-lower-bound shakedown load numerically. The proposed method is based on the computation of the three-dimensional elastic stress field numerically, and the estimation of the shakedown load iteratively via an optimisation subroutine implemented in ABAQUS. Following a short presentation of this concept, we compare the elastic stress fields from models featuring varying degree of complexity, with the aim of identifying an optimal discretisation of the problem. This approach can be used for optimising the design of ballasted track structure, and this concept is briefly presented via a parametric study. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a leading cause of blindness in the world. While dozens of independent genomic variants are associated with AMD, about one-third of AMD heritability is still unexplained. To identify novel variants and loci for AMD, we analyzed Illumina HumanExome chip data from 87 Amish individuals with early or late AMD, 79 unaffected Amish individuals, and 15 related Amish individuals with unknown AMD affection status. We retained 37,428 polymorphic autosomal variants across 175 samples for association and linkage analyses. After correcting for multiple testing (n = 37,428), we identified four variants significantly associated with AMD: rs200437673 (LCN9, p = 1.50 × 10−11), rs151214675 (RTEL1, p = 3.18 × 10−8), rs140250387 (DLGAP1, p = 4.49 × 10−7), and rs115333865 (CGRRF1, p = 1.05 × 10−6). These variants have not been previously associated with AMD and are not in linkage disequilibrium with the 52 known AMD-associated variants reported by the International AMD Genomics Consortium based on physical distance. Genome-wide significant linkage peaks were observed on chromosomes 8q21.11–q21.13 (maximum recessive HLOD = 4.03) and 18q21.2–21.32 (maximum dominant HLOD = 3.87; maximum recessive HLOD = 4.27). These loci do not overlap with loci previously linked to AMD. Through gene ontology enrichment analysis with ClueGO in Cytoscape, we determined that several genes in the 1-HLOD support interval of the chromosome 8 locus are involved in fatty acid binding and triglyceride catabolic processes, and the 1-HLOD support interval of the linkage region on chromosome 18 is enriched in genes that participate in serine-type endopeptidase inhibitor activity and the positive regulation of epithelial to mesenchymal transition. These results nominate novel variants and loci for AMD that require further investigation. [ABSTRACT FROM AUTHOR]

The original discontinuous deformation and displacement (DDD) method is greatly refined using the statistical damage theory and contact mechanics. Next, a novel coupled method is proposed to model the continuous to discontinuous failure process of rocks. By hybridizing the finite element method (FEM) and discontinuous deformation analysis (DDA) method, the proposed method inherits the advantages of both and is able to provide a complete and unified description of rock deformation, crack initiation and propagation, and rock body translation, rotation and interaction. Moreover, to improve the deformation results and refine the stress distribution within the model blocks, finite elements are introduced into the blocks. The ability of an intact block to fracture is included as well, i.e., the deformable blocks that contain several finite elements may split into smaller blocks if the strength criteria are satisfied continuously. The boundaries of damaged elements represent newly formed joints, and sliding and opening may occur along these joints, i.e., mechanical interaction is allowed between adjacent blocks. The correctness and validity of the proposed method are verified through a series of benchmark tests. The simulated results are consistent with the analytical solutions, previous studies and experimental observations. Overall, the coupled method is an effective and reliable approach for modelling the entire rock failure process with satisfactory accuracy and shows considerable potential in geotechnical engineering. [ABSTRACT FROM AUTHOR]

A series of large-scale model tests was conducted on compaction-grouted soil nails to study the influence of the degree of saturation on the soil response to compaction grouting and pull-out. The experimental results show that the initial degree of saturation of the soil strongly influences the grout injectability, thus the formed diameter of grout bulb. Subsequently, the diameter of the grout bulb alters the pull-out force, with larger grout bulbs generating higher pull-out forces and exhibiting greater hardening behaviour. Interestingly, the initial pull-out forces are the same for the same grouting pressure, regardless of the initial degree of saturation and the subsequently grout bulb. In addition, some of the main factors influencing the pressure grouting and pull-out of the soil nail, as the initial degree of saturation varies, are as follows. First, the variations in the soil pressure and density with the initial degree of saturation are similar to that of the volume of grout injected, and the compression of the soil induced by pressure grouting exhibits a similar evolution with the initial degree of saturation at different locations. Second, the initial degree of saturation of the soil sample plays a dominant role in the change in suction during pressure grouting and pull-out of soil nail. Third, the horizontal soil pressure derived from the pull-out of soil nail propagates closely in the soil sample of lower initial degree of saturation. The vertical soil pressure induced by the vertical soil dilation and squeezing effect varies in accidence with the initial degree of saturation and the grout bulb. [ABSTRACT FROM AUTHOR]

This paper presents a non-destructive, low-cost, photo-based, 3D reconstruction technique for characterizing geo-materials with irregular shapes of a relatively large size. After being validated against two traditional volume measurement methods, namely the vernier caliper method and the fluid displacement method for regular and irregular shapes, respectively, 3D photogrammetry was used to analyse the grout bulbs formed in laboratory pressure grouting tests. The reconstructed 3D mesh model of the sample provides accurate and detailed 3D vertex data, which allowed the volume, densification efficiency and bleeding behaviour of the grout bulbs to be analysed. Comparing the bulb section views at different grouting pressures also offers an intuitive observation of the grout development and propagation process. Moreover, the 3D vertex data and surface area included in the model are of great importance in validating numerical predictions of the pressure grouting process and analysing the interface shear resistance of grouted soil nails or anchors. Compared to existing approaches, the new 3D photogrammetry method possesses several key advantages: (a) it does not require expensive, specialized equipment; (b) samples are not destroyed or modified during testing; (c) it allows to reconstruct objects of various scales and (d) the software is public domain. Therefore, the adoption of this 3D photogrammetry method will facilitate research in the pressure grouting process and can be extended to other problems in geotechnical engineering. [ABSTRACT FROM AUTHOR]

The unpredictable and instantaneous collapse behaviour of coastal rocky cliffs may cause damage that extends significantly beyond the area of failure. Gravitational movements that occur during coastal cliff recession involve two major stages: the small deformation stage and the large displacement stage. In this paper, a method of simulating the entire progressive failure process of coastal rocky cliffs is developed based on the gravity increase method (GIM), the rock failure process analysis method and the discontinuous deformation analysis method, and it is referred to as the GIM-DDD method. The small deformation stage, which includes crack initiation, propagation and coalescence processes, and the large displacement stage, which includes block translation and rotation processes during the rocky cliff collapse, are modelled using the GIM-DDD method. In addition, acoustic emissions, stress field variations, crack propagation and failure mode characteristics are further analysed to provide insights that can be used to predict, prevent and minimize potential economic losses and casualties. The calculation and analytical results are consistent with previous studies, which indicate that the developed method provides an effective and reliable approach for performing rocky cliff stability evaluations and coastal cliff recession analyses and has considerable potential for improving the safety and protection of seaside cliff areas. [ABSTRACT FROM AUTHOR]

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10−7, range P = 9.2 × 10−8 to 6.0 × 10−46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10−6, range P = 5.5 × 10−6 to 6.1 × 10−35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10−54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity. [ABSTRACT FROM AUTHOR]

Purpose: Many hospitals experience one or more retained surgical item events per year, with risk of patient morbidity and medicolegal consequences. We hypothesized that the confidence and performance of the radiologist would be enhanced by prior training in retained surgical item detection and by prior exposure to commonly employed surgical instruments and devices. Methods: A training module for radiology residents was created through literature review, expert consultation, and imaging of commonly employed surgical instruments and devices. A survey assessing resident command of background knowledge, policy, and image-based retained surgical item questions was created. Additionally resident confidence for hospital policy and retained surgical item identification was assessed. A pre-module survey and confidence questionnaire were administered to first- through fourth- year residents. For one month, the training module was available online for independent review. Subsequently, a post-module survey and confidence questionnaire were completed by participants. $$T$$ tests were performed to evaluate pre- and posttest means for survey performance and confidence questions. Results: Mean post-module survey performance significantly improved compared with pre-module performance. Mean confidence levels for ability to incidentally identify a retained surgical item on a radiograph obtained for another indication and current understanding of the institution's policy regarding retained surgical items were also significantly increased. Conclusion: The knowledge base, diagnostic performance, and confidence of radiology residents were significantly enhanced by online teaching module training in retained surgical item detection. [ABSTRACT FROM AUTHOR]

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG ( p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated ( p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) was used in a prospective study of the sacroiliac joints in 86 patients with Crohn disease to determine the type and frequency of sacroiliac joint abnormalities present in this population. The CT findings were correlated with review of the clinical history in 64 patients. Computed tomography demonstrated changes of sacroiliitis in 29% of the study group. This high prevalence of sacroiliac joint abnormality was found even in those under 30 years of age. It exceeds the 11-19% previously reported from plain film examination, reflecting the greater sensitivity of CT. In the subgroup of 64 patients studied clinically, 19 (30%) had abnormal sacroiliac joints on CT, but only 2 (3%) reported symptoms related to the sacroiliac joints. [ABSTRACT FROM AUTHOR]

Purpose: Endometriosis is a common disease; however, ectopic müllerian tissue within the spine is a rare entity with the potential for producing significant neurological compromise. There are several postulated etiologies for this phenomenon, and only a few case reports are available in the world literature. Knowledge of this rare phenomenon is of paramount importance, since early diagnosis can lead to lessened neurological morbidity. Methods: In this manuscript, we present a case report, discuss gynecological and neurosurgical perspectives relating to the treatment strategies for managing this entity, and propose an alternative explanation for such an occurrence from a neurogenetic standpoint. Results: We present a case of spinal müllerianosis within the conus medullaris which was managed symptomatically for several years with an intracystic drain and subcutaneous reservoir. Over the years, it became clear that there was a cyclical presentation to her clinical malady, which at times was severe. Ultimately, she required surgical resection which aided in her diagnosis and subsequent treatment. Conclusion: Intraspinal müllerianosis is a rare location for an otherwise common disease in women and has the potential to create significant neurological morbidity by creating a mass lesion. Although the exact etiology remains unclear, the histogenic theories of embryologic origin appear most plausible. Treatment strategies for this condition may include hormonal therapy, obstetrical surgery, or open spinal surgery. This unusual and poorly understood disease should be considered in the differential diagnosis for intraspinal lesions presenting with hemorrhage in the clinical context of cyclical neurological symptoms. [ABSTRACT FROM AUTHOR]

Pediatric cardiothoracic surgery is often associated with low cardiac output in the postoperative period. This study sought to determine whether increasing heart rate via temporary atrial pacing is beneficial in augmenting cardiac output. Patients younger than 18 years who underwent cardiothoracic surgery and had no perioperative arrhythmias were eligible for the study. Patients not paced postoperatively were atrial paced at a rate of 15 % above the intrinsic sinus rate (not to exceed 170 beats per minute, less for older patients) for 15 min. Patients paced for cardiac output postoperatively had their pacemakers paused for 15 min. Markers of cardiac output were measured before and after the intervention. Of the 60 patients who consented to participate, 30 completed the study. Failure to complete the study was due to tachycardia ( n = 13), lack of pacing wires ( n = 7), junctional rhythm ( n = 4), advanced atrioventricular block ( n = 3), and other cause ( n = 3). Three patients were paced at baseline. There was no change in arteriovenous oxygen saturation difference, mean arterial blood pressure, central venous pressure, toe temperature, or lactate with atrial pacing. Atrial pacing was associated with a decrease in head and flank near-infrared spectroscopy ( p = 0.01 and <0.01 respectively). Secondary analysis found an inverse relationship between mean arterial pressure response to pacing and bypass time. Temporary atrial pacing does not improve cardiac output after pediatric cardiac surgery and may be deleterious. Future research may identify subsets of patients who benefit from this strategy. Practitioners considering this strategy should carefully evaluate each patient's response to atrial pacing before its implementation. [ABSTRACT FROM AUTHOR]

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Successful aging (SA) is a multidimensional phenotype involving living to older age with high physical function, preserved cognition, and continued social engagement. Several domains underlying SA are heritable, and identifying health-promoting polymorphisms and their interactions with the environment could provide important information regarding the health of older adults. In the present study, we examined 263 cognitively intact Amish individuals age 80 and older (74 SA and 189 'normally aged') all of whom are part of a single 13-generation pedigree. A genome-wide association study of 630,309 autosomal single nucleotide polymorphisms (SNPs) was performed and analyzed for linkage using multipoint analyses and for association using the modified quasi-likelihood score test. There was evidence for linkage on 6q25-27 near the fragile site FRA6E region with a dominant model maximum multipoint heterogeneity LOD score = 3.2. The 1-LOD-down support interval for this linkage contained one SNP for which there was regionally significant evidence of association (rs205990, p = 2.36 × 10). This marker survived interval-wide Bonferroni correction for multiple testing and was located between the genes QKI and PDE10A. Other areas of chromosome 6q25-q27 (including the FRA6E region) contained several SNPs associated with SA (minimum p = 2.89 × 10). These findings suggest potentially novel genes in the 6q25-q27 region linked and associated with SA in the Amish; however, these findings should be verified in an independent replication cohort. [ABSTRACT FROM AUTHOR]

Recent software developments enable interactive, real-time axial, 2D and 3D CT display on an iPad by cloud computing from a server for remote rendering. The purpose of this study was to compare radiologists' interpretative performance on the iPad to interpretation on the conventional picture archive and communication system (PACS). Fifty de-identified contrast-enhanced CT exams performed for suspected pulmonary embolism were compiled as an educational tool to prepare our residents for night call. Two junior radiology attendings blindly interpreted the cases twice, one reader used the PACS first, and the other interpreted on the iPad first. After an interval of at least 2 weeks, the cases were reinterpreted in different order using the other display technique. Sensitivity, specificity, and accuracy for identification of pulmonary embolism were compared for each interpretation method. Pulmonary embolism was present in 25 patients, ranging from main pulmonary artery to subsegmental thrombi. Both readers interpreted 98 % of cases correctly regardless of display platform. There was no significant difference in sensitivity (98 vs 100 %, p = 1.0), specificity (98 vs 96 %, p = 1.0), or accuracy (98 vs 98 %, p = 1.0) for interpretation with the iPad vs the PACS, respectively. CT interpretation on an iPad enabled accurate identification of pulmonary embolism, equivalent to display on the PACS. This mobile device has the potential to expand radiologists' availability for consultation and expedite emergency patient management. [ABSTRACT FROM AUTHOR]

Avoiding disease, maintaining physical and cognitive function, and continued social engagement in long-lived individuals describe successful aging (SA). Mitochondrial lineages described by patterns of common genetic variants ('haplogroups') have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on SA in an Amish community sample. Cognitively intact volunteers aged ≥80 years ( n = 261) were enrolled in a door-to-door survey of Amish communities in Indiana and Ohio. Individuals scoring in the top third for lower extremity function, needing little assistance with self-care tasks, having no depression symptoms, and expressing high life satisfaction were considered SA ( n = 74). The remainder ( n = 187) were retained as controls. These individuals descend from 51 matrilines in a single 13-generation pedigree. Mitochondrial haplogroups were assigned using the ten mitochondrial single nucleotide polymorphisms (mtSNPs) defining the nine most common European haplogroups. An additional 17 mtSNPs from a genome-wide association panel were also investigated. Associations between haplogroups, mtSNPs, and SA were determined by logistic regression models accounting for sex, age, body mass index, and matriline via generalized estimating equations. SA cases were more likely to carry Haplogroup X (OR = 7.56, p = 0.0015), and less likely to carry Haplogroup J (OR = 0.40, p = 0.0003). Our results represent a novel association of Haplogroup X with SA and suggest that variants in the mitochondrial genome may promote maintenance of both physical and cognitive function in older adults. [ABSTRACT FROM AUTHOR]

Gastric pneumatosis is rare, with causes ranging from benign to lethal. The purpose of this pictorial essay is to present a series of cases of gastric pneumatosis, review the causes, and demonstrate how computed tomography (CT) can help guide management. A range of primary gastric pathology can cause air in the wall of the stomach. However, gastric pneumatosis may reflect intraabdominal pathology arising from other hollow viscera, with indicators of the extragastric etiology on CT. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 × 10−9) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 × 10−8), which replicated in two datasets (meta-analysis P = 1.9 × 10−10). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 × 10−10) and late-onset (P = 2.4 × 10−8) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development. [ABSTRACT FROM AUTHOR]

Controversy remains as to which gene at the chromosome 10q26 locus confers risk for age-related macular degeneration (AMD) and statistical genetic analysis is confounded by the strong linkage disequilibrium (LD) across the region. Functional analysis of related genetic variations could solve this puzzle. Recently, Fritsche et al. reported that AMD is associated with unstable ARMS2 transcripts possibly caused by a complex insertion/deletion (indel; consisting of a 443 bp deletion and an adjacent 54 bp insertion) in its 3′UTR (untranslated region). To validate this indel, we sequenced our samples. We found that this indel is even more complex and is composed of two side-by-side indels separated by 17 bp: (1) 9 bp deletion with 10 bp insertion; (2) 417 bp deletion with 27 bp insertion. The indel is significantly associated with the risk of AMD, but is also in strong LD with the non-synonymous single nucleotide polymorphism rs10490924 (A69S). We also found that ARMS2 is expressed not only in placenta and retina but also in multiple human tissues. Using quantitative PCR, we found no correlation between the indel and ARMS2 mRNA level in human retina and blood samples. The lack of functional effects of the 3′UTR indel, the amino acid substitution of rs10490924 (A69S), and strong LD between them suggest that A69S, not the indel, is the variant that confers risk of AMD. To our knowledge, it is the first time it has been shown that ARMS2 is widely expressed in human tissues. Conclusively, the indel at 3′UTR of ARMS2 actually contains two side-by-side indels. The indels are associated with risk of AMD, but not correlated with ARMS2 mRNA level. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ ( TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (−196 to −174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24–0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51–0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) has substantial mortality worldwide with 5–10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case–control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23–2.77], p = 0.003) and rs7215373 (OR = 1.67, 95% CI [1.17–2.37], p = 0.004), both of which passed a false discovery rate correction for multiple comparisons ( q* = 0.20). The strongest gene–gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 ( p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 ( p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1. [ABSTRACT FROM AUTHOR]