1,038 research outputs found
Complete Ulcer Healing as a Primary Endpoint in Studies on Critical Limb Ischemia (Hoffman et al)
Thoracoabdominal Aortic Surgery With Special Reference to Spinal Cord Protection and Perfusion Techniques
The capacitance of the circular parallel plate capacitor obtained by solving the Love integral equation using an analytic expansion of the kernel
The capacitance of the circular parallel plate capacitor is calculated by
expanding the solution to the Love integral equation into a Fourier cosine
series. Previously, this kind of expansion has been carried out numerically,
resulting in accuracy problems at small plate separations. We show that this
bottleneck can be alleviated, by calculating all expansion integrals
analytically in terms of the Sine and Cosine integrals. Hence, we can, in the
approximation of the kernel, use considerably larger matrices, resulting in
improved numerical accuracy for the capacitance. In order to improve the
accuracy at the smallest separations, we develop a heuristic extrapolation
scheme that takes into account the convergence properties of the algorithm. Our
results are compared with other numerical results from the literature and with
the Kirchhoff result. Error estimates are presented, from which we conclude
that our results is a substantial improvement compared with earlier numerical
results.Comment: 15 pages, 3 figure
Reticuloendothelial System Function Following Acute Liver Failure Induced by 90% Hepatectomy in the Rat
Sepsis and bacterial infections are frequent complications of acute liver failure and following major liver resection. The mechanisms underlying this phenomenon are unclear. In this study, RES function and blood clearance of radiolabelled E. coli was immediately impaired following 90% hepatectomy, although the reduction in liver volume resulted in an increase in splenic (temporary) and pulmonary (persisting) uptake. A significant correlation between liver function and host RES function was observed. The uptake capacity of the RES in the liver remnant and spleen did not correlate with subserosal blood flow. The uptake in the brain gradually increased with time, paralleling an increased leakage across the blood-brain barrier. Thus, a significantly impaired RES function resulted from experimental 90% hepatectomy-induced acute liver failure, which might explain the high incidence of septic events in the clinical situation
Insights on the Role of Diabetes and Geographic Variation in Patients with Criticial Limb Ischaemia
AbstractBackgroundPatients with critical limb ischaemia (CLI) unsuitable for revascularisation have a high rate of amputation and mortality (30% and 25% at 1 year, respectively). Localised gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pecaplasmid) has showed an increased amputation-free survival in a phase II trial. This article provides the rationale, design and baseline characteristics of CLI patients enrolled in the pivotal phase III trial (EFC6145/TAMARIS).MethodsAn international, double-blind, placebo-controlled, randomised study composed of 525 CLI patients recruited from 170 sites worldwide who were unsuitable for revascularisation and had non-healing skin lesions was carried out to evaluate the potential benefit of repeated intramuscular administration of NV1FGF. Randomisation was stratified by country and by diabetic status.ResultsThe mean age of the study cohort was 70 ± 10 years, and included 70% males and 53% diabetic patients. Fifty-four percent of the patients had previous lower-extremity revascularisation and 22% had previous minor amputation of the index leg. In 94% of the patients, the index leg had distal occlusive disease affecting arteries below the knee. Statins were prescribed for 54% of the patients, and anti-platelet drugs for 80%. Variation in region of origin resulted in only minor demographic imbalance. Similarly, while diabetic status was associated with a frequent history of coronary artery disease, it had little impact on limb haemodynamics and vascular lesions.ConclusionsClinical characteristics and vascular anatomy of CLI patients with ischaemic skin lesions who were unsuitable for revascularisation therapy show little variations by region of origin and diabetic status. The findings from this large CLI cohort will contribute to our understanding of this disease process.This study is registered with ClinicalTrials.gov, number NCT00566657
Single Nucleotide Polymorphisms (SNPs) Distinguish Indian-Origin and Chinese-Origin Rhesus Macaques (Macaca Mulatta)
BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3\u27 end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis.
RESULTS: We surveyed the 3\u27 end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific.
CONCLUSION: This study demonstrates that the 3\u27 end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations
Single nucleotide polymorphisms (SNPs) distinguish Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta)
BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations
Environmental chemicals change extracellular lipidome of mature human white adipocytes
Funding This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement GOLIATH grant No. 825489 and Swedish Research Council for Sustainable Development (FORMAS) grant No. 2019-00375.Peer reviewedPublisher PD
Leveraging human genomic information to identify nonhuman primate sequences for expression array development
BACKGROUND: Nonhuman primates (NHPs) are essential for biomedical research due to their similarities to humans. The utility of NHPs will be greatly increased by the application of genomics-based approaches such as gene expression profiling. Sequence information from the 3' end of genes is the key resource needed to create oligonucleotide expression arrays. RESULTS: We have developed the algorithms and procedures necessary to quickly acquire sequence information from the 3' end of nonhuman primate orthologs of human genes. To accomplish this, we identified terminal exons of over 15,000 human genes by aligning mRNA sequences with genomic sequence. We found the mean length of complete last exons to be approximately 1,400 bp, significantly longer than previous estimates. We designed primers to amplify genomic DNA, which included at least 300 bp of the terminal exon. We cloned and sequenced the PCR products representing over 5,500 Macaca mulatta (rhesus monkey) orthologs of human genes. This sequence information has been used to select probes for rhesus gene expression profiling. We have also tested 10 sets of primers with genomic DNA from Macaca fascicularis (Cynomolgus monkey), Papio hamadryas (Baboon), and Chlorocebus aethiops (African green monkey, vervet). The results indicate that the primers developed for this study will be useful for acquiring sequence from the 3' end of genes for other nonhuman primate species. CONCLUSION: This study demonstrates that human genomic DNA sequence can be leveraged to obtain sequence from the 3' end of NHP orthologs and that this sequence can then be used to generate NHP oligonucleotide microarrays. Affymetrix and Agilent used sequences obtained with this approach in the design of their rhesus macaque oligonucleotide microarrays
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