Time resolved three-dimensional (3D) echocardiography generates four-dimensional (3D+time) data sets that bring new possibilities in clinical practice. Image quality of four-dimensional (4D) ...echocardiography is however regarded as poorer compared to conventional echocardiography where time-resolved 2D imaging is used. Advanced image processing filtering methods can be used to achieve image improvements but to the cost of heavy data processing. The recent development of graphics processing unit (GPUs) enables highly parallel general purpose computations, that considerably reduces the computational time of advanced image filtering methods. In this study multidimensional adaptive filtering of 4D echocardiography was performed using GPUs. Filtering was done using multiple kernels implemented in OpenCL (open computing language) working on multiple subsets of the data. Our results show a substantial speed increase of up to 74 times, resulting in a total filtering time less than 30 s on a common desktop. This implies that advanced adaptive image processing can be accomplished in conjunction with a clinical examination. Since the presented GPU processor method scales linearly with the number of processing elements, we expect it to continue scaling with the expected future increases in number of processing elements. This should be contrasted with the increases in data set sizes in the near future following the further improvements in ultrasound probes and measuring devices. It is concluded that GPUs facilitate the use of demanding adaptive image filtering techniques that in turn enhance 4D echocardiographic data sets. The presented general methodology of implementing parallelism using GPUs is also applicable for other medical modalities that generate multidimensional data.
Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on ...causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 x 10.sup.-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) greater than or equal to 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
To investigate crack initiation and propagation in reinforced, self-compacting, steel–fibre-reinforced concrete (SCSFRC) members, tie elements were tested in tension. Strain and surface crack ...formation were monitored with an optical strain measurement system based on digital image correlation. In addition, to capture the softening behaviour (
σ
–
w
) of the material, uni-axial tension testing was performed on SCSFRC cylinders. The results show that, with the optical strain measurement system, it was possible to detect different cracking modes and to follow the crack growth. It was especially of interest to recognize that high fibre amounts tend to change a sudden opening of a crack (as in non-fibrous concrete) into a more stable procedure. It was found that, for a given crack width, the SCSFRC specimens exhibited a noticeably higher tension stiffening than the specimens without fibres. Moreover, at a given load, the crack widths decreased by as much as 65% for the SCSFRC specimens with a nominal fibre content of 1%. For the uni-axial tension tests the results showed that with higher fibre content, for this type of fibre and concrete, both the peak stress and the residual tensile stress were increased. Additionally, it was noted for both specimen types that the scatter in fibre distribution decreased with increasing fibre content.
This study examined the effects of weight loss and nutritional status on the cognitive performance of patients with anorexia nervosa. The intellectual, memory, attentional, verbal fluency and ...visuospatial abilities of 34 females with anorexia were compared to that of 31 normal weight-for-height females. Group differences in anxiety and depression were found but neither variable was related to the cognitive performance of patients with anorexia. Moreover, nutritional status and weight loss bore little relationship to the cognitive scores of the patient group. Overall, patients with anorexia were found to be deficient in their ability to recall meaningful prose and visuospatial information. The failure to find many cognitive deficits in this sample may reflect the fact that few patients with anorexia exhibited frank nutritional deficiencies.
Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective ...studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.
Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, ...selective, competitive PAR-1 antagonist. We designed TRA•CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non–ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA•CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least 1 year. The TRA•CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA•CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole ...genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.
Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and ...replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.
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