Measuring aortic pulse wave velocity using high-field cardiovascular magnetic resonance: comparison of techniques

<p>Abstract</p> <p>Background</p> <p>The assessment of arterial stiffness is increasingly used for evaluating patients with different cardiovascular diseases as the mechanical properties of major arteries are often altered. Aortic stiffness can be noninvasively estimated by measuring pulse wave velocity (PWV). Several methods have been proposed for measuring PWV using velocity-encoded cardiovascular magnetic resonance (CMR), including transit-time (TT), flow-area (QA), and cross-correlation (XC) methods. However, assessment and comparison of these techniques at high field strength has not yet been performed. In this work, the TT, QA, and XC techniques were clinically tested at 3 Tesla and compared to each other.</p> <p>Methods</p> <p>Fifty cardiovascular patients and six volunteers were scanned to acquire the necessary images. The six volunteer scans were performed twice to test inter-scan reproducibility. Patient images were analyzed using the TT, XC, and QA methods to determine PWV. Two observers analyzed the images to determine inter-observer and intra-observer variabilities. The PWV measurements by the three methods were compared to each other to test inter-method variability. To illustrate the importance of PWV using CMR, the degree of aortic stiffness was assessed using PWV and related to LV dysfunction in five patients with diastolic heart failure patients and five matched volunteers.</p> <p>Results</p> <p>The inter-observer and intra-observer variability results showed no bias between the different techniques. The TT and XC results were more reproducible than the QA; the mean (SD) inter-observer/intra-observer PWV differences were -0.12(1.3)/-0.04(0.4) for TT, 0.2(1.3)/0.09(0.9) for XC, and 0.6(1.6)/0.2(1.4) m/s for QA methods, respectively. The correlation coefficients (r) for the inter-observer/intra-observer comparisons were 0.94/0.99, 0.88/0.94, and 0.83/0.92 for the TT, XC, and QA methods, respectively. The inter-scan reproducibility results showed low variability between the repeated scans (mean (SD) PWV difference = -0.02(0.4) m/s and r = 0.96). The inter-method variability results showed strong correlation between the TT and XC measurements, but less correlation with QA: r = 0.95, 0.87, and 0.89, and mean (SD) PWV differences = -0.12(1.0), 0.8(1.7), and 0.65(1.6) m/s for TT-XC, TT-QA, and XC-QA, respectively. Finally, in the group of diastolic heart failure patient, PWV was significantly higher (6.3 ± 1.9 m/s) than in volunteers (3.5 ± 1.4 m/s), and the degree of LV diastolic dysfunction showed good correlation with aortic PWV.</p> <p>Conclusions</p> <p>In conclusion, while each of the studied methods has its own advantages and disadvantages, at high field strength, the TT and XC methods result in closer and more reproducible aortic PWV measurements, and the associated image processing requires less user interaction, than in the QA method. The choice of the analysis technique depends on the vessel segment geometry and available image quality.</p

Measuring Changes in Brain Metabolite Levels Using Live-animal Magnetic Resonance Spectroscopy and Offline LC-MS Metabolomics in a Binge-ethanol Murine Model

Alcoholism and acute alcohol binge are significant public health concerns. Liquid chromatography-mass spectrometry (LC-MS) based metabolomics is a robust and sensitive technique for determining and quantifying transient or permanent biochemical changes within the central nervous system (CNS). However, access to human tissue and CNS biofluid for such analyses is limited in a clinical context. In-vivo magnetic resonance spectroscopy (MRS) is an attractive alternative for clinical measurement but currently the technique is limited to a small to a number of well-characterized, highly abundant analytes. We therefore seek to correlate LC-MS and MRS measurements to better understand and leverage the strengths of each. Following live animal MRS measurement, metabolites in hippocampal brain punch homogenates were quantified by LC-MS, and a Spearman’s correlation coefficient was calculated. We found that the measurements for glutamine and glutamate,, were significantly correlated. Other established neurochemicals, including NAA and aspartate, showed non-significant correlations. NAAG showed little correlation between the two measurements. Additional experiments are ongoing to resolve these discrepancies, and determine how to achieve better agreement between the two methods. In addition,, we used Elements (Proteome Software) to determine differentially expressed metabolites between ethanol exposed and control mice.. An initial pass shows more than 1000 peak-picked features identified in the two conditions, with approximately 200 analytes identified in the metabolite database (human) based on accurate mass. Differentially expressed candidates can be validated further using tandem mass spectrometry and, where possible, the use of authentic standards. Metabolites that change after binge ethanol exposure are reported along with an overview of comparing MRS with LC-MS datasets

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135043/1/mp8118.pd

Improving Outcomes in Infants of HIV-Infected Women in a Developing Country Setting

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant

How society’s negative view of videogames can discourage brands from sponsoring eSports

The purpose of this research was to identify the main motives that contribute to society’s negative view of videogames and that present a risk to the eSports sponsors’ image. To achieve this, an exploratory, qualitative, and integrative literature review was conducted. According to the theoretical data, there are four main reasons why society has a negative perception of videogames. It is commonly believed that: (1) gaming is an unproductive activity, (2) violent videogames incite aggressive behaviors, (3) videogames lead to gaming-addiction, and (4) eSports lead to eSports-related gambling addiction. However, while the literature presents convincing evidence that gaming can create addiction and that eSports can promote gambling addiction, there is no conclusive evidence to assume that violent videogames lead to aggressiveness and there is evidence showing that playing videogames can be a productive activity. Nevertheless, these four beliefs are a threat to the eSports sponsors’ image and may lead them to cancel their existing sponsorships or lead other brands to not want to sponsor eSports to prevent being associated with these negative notions. This research will help expand the minor literature on eSports sponsorships and advance the knowledge of why some eSports sponsorships are terminated and why some brands may be reluctant to sponsor eSports.info:eu-repo/semantics/publishedVersio

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10−12). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development

Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS)