Combined Carpal Tunnel Release and Palmar Fasciectomy for Dupuytren’s Contracture Does Not Increase the Risk for Complex Regional Pain Syndrome

Background: Hand surgery dogma suggests that simultaneous surgical treatment of carpal tunnel syndrome (CTS) and Dupuytren’s contracture (DC) results in an increased incidence of Complex Regional Pain Syndrome (CRPS). As a result, many surgeons do not perform surgery for the two conditions concurrently. Our goal was to determine the extent of this association. Methods: We identified all patients undergoing surgical treatment for CTS, DC, or both between April 1982 and March 2017 using the Indiana Network for Patient Care (INPC), a large, multi-institutional, statewide information exchange. Demographics, comorbidities, and 1-year post-operative incidence of CRPS were recorded. Results: A total of 51,739 (95.6%) patients underwent carpal tunnel release (CTR) only, 2,103 (3.9%) underwent palmar fasciectomy (PF) only, and 305 (0.6%) underwent concurrent CTR and PF. There was no difference in the likelihood of developing CRPS (p=0.163) between groups. Independent risk factors for developing CRPS were younger age, anxiety, depression, epilepsy, gout, and history of fracture of the radius, ulna, or the carpus. Conclusions: Concurrent CTR and PF is not associated with an increased risk for developing CRPS. Patient demographics, medical comorbidities, and a history of upper extremity trauma are associated with the development of CRPS after surgery and should be discussed preoperatively as potential risk factors

Unbiased Shape Compactness for Segmentation

We propose to constrain segmentation functionals with a dimensionless, unbiased and position-independent shape compactness prior, which we solve efficiently with an alternating direction method of multipliers (ADMM). Involving a squared sum of pairwise potentials, our prior results in a challenging high-order optimization problem, which involves dense (fully connected) graphs. We split the problem into a sequence of easier sub-problems, each performed efficiently at each iteration: (i) a sparse-matrix inversion based on Woodbury identity, (ii) a closed-form solution of a cubic equation and (iii) a graph-cut update of a sub-modular pairwise sub-problem with a sparse graph. We deploy our prior in an energy minimization, in conjunction with a supervised classifier term based on CNNs and standard regularization constraints. We demonstrate the usefulness of our energy in several medical applications. In particular, we report comprehensive evaluations of our fully automated algorithm over 40 subjects, showing a competitive performance for the challenging task of abdominal aorta segmentation in MRI.Comment: Accepted at MICCAI 201

Athena

The Athena simulation software supports an analyst from DoD or other federal agency in making stability and reconstruction projections for operational analyses in areas like Iraq or Afghanistan. It encompasses the use of all elements of national power: diplomatic, information, military, and economic (DIME), and anticipates their effects on political, military, economic, social, information, and infrastructure (PMESII) variables in real-world battle space environments. Athena is a stand-alone model that provides analysts with insights into the effectiveness of complex operations by anticipating second-, third-, and higher-order effects. For example, the first-order effect of executing a curfew may be to reduce insurgent activity, but it may also reduce consumer spending and keep workers home as second-order effects. Reduced spending and reduced labor may reduce the gross domestic product (GDP) as a third-order effect. Damage to the economy will have further consequences. The Athena approach has also been considered for application in studies related to climate change and the smart grid. It can be applied to any project where the impacts on the population and their perceptions are important, and where population perception is important to the success of the project

Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets

GRSDB2 and GRS_UTRdb: databases of quadruplex forming G-rich sequences in pre-mRNAs and mRNAs

G-quadruplex motifs in the RNA play significant roles in key cellular processes and human disease. While sequences capable of forming G-quadruplexes in the pre-mRNA are involved in regulation of polyadenylation and splicing events in mammalian transcripts, the G-quadruplex motifs in the UTRs may help regulate mRNA expression. GRSDB2 is a second-generation database containing information on the composition and distribution of putative Quadruplex-forming G-Rich Sequences (QGRS) mapped in ∼29 000 eukaryotic pre-mRNA sequences, many of which are alternatively processed. The data stored in the GRSDB2 is based on computational analysis of NCBI Entrez Gene entries with the help of an improved version of the QGRS Mapper program. The database allows complex queries with a wide variety of parameters, including Gene Ontology terms. The data is displayed in a variety of formats with several additional computational capabilities. We have also developed a new database, GRS_UTRdb, containing information on the composition and distribution patterns of putative QGRS in the 5′- and 3′-UTRs of eukaryotic mRNA sequences. The goal of these experiments has been to build freely accessible resources for exploring the role of G-quadruplex structure in regulation of gene expression at post-transcriptional level. The databases can be accessed at the G-Quadruplex Resource Site at: http://bioinformatics.ramapo.edu/GQRS/

Aberrant Splicing of the Senataxin Gene in a Patient with Ataxia with Oculomotor Apraxia Type 2

Ataxia with oculomotor apraxia type 2 (AOA2) is caused by a diversity of mutations within the coding region of the senataxin gene. Recently, rare noncoding senataxin mutations affecting RNA processing have been identified in AOA2. Here, we report the case of an 18-year-old woman, with classic clinical features of AOA2, who was found to harbor a mutation within senataxin intron 16. This mutation disrupts the local 5′ splice site architecture via a novel intronic frameshift mechanism, causing skipping of exon 16 with predicted disruption of the conserved DNA/RNA helicase domain. RNA processing mutations expand the growing complexity of pathogenic senataxin mutations

Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2

<p>Abstract</p> <p>Background</p> <p>The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (<it>SETX</it>). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions.</p> <p>Methods</p> <p>To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the <it>SETX </it>gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined.</p> <p>Results</p> <p>Sequence analyses of the <it>SETX </it>gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4.</p> <p>Conclusion</p> <p>Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics.</p

Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10-8, odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10-5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use

A study on missing lines in the synthetic solar spectrum near the Ca triplet

Synthetic stellar spectra are extensively used for many different applications in astronomy, from stellar studies (such as in the determination of atmospheric parameters of observed stellar spectra), to extragalactic studies (e.g. as one of the main ingredients of stellar population models). One of the main ingredients of synthetic spectral libraries are the atomic and molecular line lists, which contain the data required to model all the absorption lines that should appear in these spectra. Although currently available line lists contain millions of lines, a relatively small fraction of these lines have accurate derived or measured transition parameters. As a consequence, many of these lines contain errors in the electronic transition parameters that can reach up to 200%. Furthermore, even for the Sun, our closest and most studied star, state-of-the-art synthetic spectra does not reproduce all the observed lines, indicating transitions that are missing in the line lists of the computed synthetic spectra. Given the importance and wide range of applications of these models, improvement of their quality is urgently necessary. In this work we catalogued missing lines in the atomic and molecular line lists used for the calculation of the synthetic spectra in the region of GAIA, comparing a solar model computed via a recent line list with a high quality solar atlas available in the literature. After that, we attempted the calibration of their atomic parameters with the code ALLiCE; the calibrated line parameters are publicly available for use