90 research outputs found
cuIBM -- A GPU-accelerated Immersed Boundary Method
A projection-based immersed boundary method is dominated by sparse linear
algebra routines. Using the open-source Cusp library, we observe a speedup
(with respect to a single CPU core) which reflects the constraints of a
bandwidth-dominated problem on the GPU. Nevertheless, GPUs offer the capacity
to solve large problems on commodity hardware. This work includes validation
and a convergence study of the GPU-accelerated IBM, and various optimizations.Comment: Extended paper post-conference, presented at the 23rd International
Conference on Parallel Computational Fluid Dynamics (http://www.parcfd.org),
ParCFD 2011, Barcelona (unpublished
Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections
Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging
Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.
Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype
Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis
Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic
variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary
arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.
Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial
hypertension. These GWAS used data from four international case-control studies across 11744 individuals with
European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and
the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching
genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants
at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and
tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.
Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10–
¹⁵) and a second locus in
HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71],
p=7·65×10–
²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus
had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48],
p=1·69×10–
¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene
regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined
haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The
HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in
patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI
12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity.
Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in
HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more
common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed
to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA
typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.
Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA,
ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and
RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR
Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
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