Telomere Length, Proviral Load and Neurologic Impairment in HTLV-1 and HTLV-2-Infected Subjects.

Short or damaged telomeres have been implicated in degenerative conditions. We hypothesized that analysis of telomere length (TL) in human T-cell lymphotropic virus (HTLV) infection and HTLV-associated neuropathy might provide clues to the etiology of HTLV-associated disease and viral dynamics. A subset of 45 human T-cell lymphotropic virus type 1 (HTLV-1), 45 human T-cell lymphotropic virus type 2 (HTLV-2), and 45 seronegative subjects was selected from the larger HTLV Outcomes Study (HOST) cohort, matched on age, sex and race/ethnicity. Telomere-to-single-copy gene (T/S) ratio (a measure of TL) and HTLV-1 and HTLV-2 proviral loads were measured in peripheral blood mononuclear cells (PBMCs) using quantitative PCR (qPCR). Vibration sensation measured by tuning fork during neurologic examinations performed as part of the HOST study allowed for an assessment of peripheral neuropathy. TL was compared between groups using t-tests, linear and logistic regression. Mean T/S ratio was 1.02 ± 0.16 in HTLV-1, 1.03 ± 0.17 in HTLV-2 and 0.99 ± 0.18 in HTLV seronegative subjects (p = 0.322). TL was not associated with HTLV-1 or -2 proviral load. Shorter TL was significantly associated with impaired vibration sense in the HTLV-2 positive group only. Overall, we found no evidence that telomere length was affected by chronic HTLV-1 and HTLV-2 infection. That TL was only associated with peripheral neuropathy in the HTLV-2-positive group is intriguing, but should be interpreted cautiously. Studies with larger sample size and telomere length measurement in lymphocyte subsets may clarify the relationship between TL and HTLV-infection

Efficacy of recombinant human granulocyte colony stimulating factor in very-low-birth-weight infants with early neutropenia

Background/PurposeNeutropenia is a risk factor for nosocomial infections (NI) in very-low-birth-weight (VLBW) infants. Although recombinant human granulocyte colony stimulating factor (rhG-CSF) increases the neutrophil counts in neutropenic VLBW infants, its long-term efficacy for early neutropenia (EN) remains unknown.MethodsIn this case-controlled study, charts of VLBW recipients of rhG-CSF for EN (total neutrophil count <1.5 × 109/L during first 7 days) were reviewed and compared to gestational age, total neutrophil count, and birth weight matched infants unexposed to rhG-CSF.ResultsTwenty-seven infants were identified in each group. Mortality and morbidity did not differ between the two groups. Rate of NI (16/27 vs. 4/27, p = 0.002, odds ratio = 8.36) as well as the total number of episodes of NI (22 vs. 4, p = 0.007) were higher in rhG-CSF (+) group than in the rhG-CSF (–) group.ConclusionOur experience does not show benefit in empirical use of rhG-CSF in preventing NI in VLBW infants with EN

Design of optimally smoothing multistage schemes for the euler equations

A recently derived local preconditioning of the Euler equations is shown to be useful in developing multistage schemes suited for multigrid use. The effect of the preconditioning matrix on the spatial Euler operator is to equalize the characteristic speeds. When applied to the discretized Euler equations, the preconditioning has the effect of strongly clustering the operator's eigenvalues in the complex plane. This makes possible the development of explicit marching schemes that effectively damp most high‐frequency Fourier modes, as desired in multigrid applications. The technique is the same as developed earlier for scalar convection schemes: placement of the zeros of the amplification factor of the multistage scheme in locations where eigenvalues corresponding to high‐frequency modes abound.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111971/1/1630081006_ftp.pd

Non-contact 3D acquisition system based on stereo vision and laser triangulation

This paper proposes a novel contact 3D acquisition system based on stereo vision and laser triangulation. The system is composed by several software modules for data acquisition purposes, data calibration, data processing and data reconstruction of 3D scenes. Different 3D image techniques, such as, polynomial determination, cubic spline interpolation and hierarchical space decomposition were used. To validate this method, a simple laboratory prototype machine was built for the purpose of road profile acquisition, road macro and mega texture characterization. In this paper, only the results and discussion of road profile acquisition are presented.Fundação para a Ciência e a Tecnologia (FCT

Modeling Noise Coupling Between Package and PCB Power/Ground Planes with an Efficient 2-D FDTD/Lumped Element Method

An efficient numerical approach based on the 2-D finite-difference time-domain (FDTD) method is proposed to model the power/ground plane noise or simultaneously switching noise (SSN), including the interconnect effect between the package and the print circuit board (PCB). The space between the power and ground planes on the package and PCB are meshed with 2-D cells. The equivalent R-L-C circuits of the via and the solder balls connecting the package and PCB can be incorporated into a 2-D Yee cell based on a novel integral formulation in the time domain. An efficient recursive updating algorithm is proposed to fit the lumped networks into the Yee equations. A test sample of a ball grid array (BGA) package mounted on a PCB was fabricated. The power/ground noise coupling behavior was measured and compared with the simulation. The proposed method significantly reduces the computing time compared with other full-wave numerical approaches

Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 &#x2013; 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 &#x2013; 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 &#x2013; 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Control Charts for Monitoring Burr Type-X Percentiles

[[abstract]]When the sampling distribution of a parameter estimator is unknown, using normality asymptotically, the Shewhart-type chart may provide improper control limits. To monitor Burr type-X percentiles, two parametric bootstrap charts (PBCs) are proposed and compared with the Shewhart-type chart via a Monte Carlo simulation. Simulation results exhibit that the proposed PBCs perform well with a short average run length to signal out-of-control when the process is out-of-control, and have more adequate control limits than the Shewhart-type chart in view of in-control false alarm rate. An example regarding single fiber strength is presented for illustrating the proposed PBCs.[[incitationindex]]SCI[[booktype]]紙

Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer

BACKGROUND: Most women with a clinical presentation consistent with ovarian cancer have benign conditions. Therefore methods to distinguish women with ovarian cancer from those with benign conditions would be beneficial. We describe the development and preliminary evaluation of a serum-based multivariate assay for ovarian cancer. This hypothesis-driven study examined whether an informative pattern could be detected in stage I disease that persists through later stages. METHODOLOGY/PRINCIPAL FINDINGS: Sera, collected under uniform protocols from multiple institutions, representing 176 cases and 187 controls from women presenting for surgery were examined using high-throughput, multiplexed immunoassays. All stages and common subtypes of epithelial ovarian cancer, and the most common benign ovarian conditions were represented. A panel of 104 antigens, 44 autoimmune and 56 infectious disease markers were assayed and informative combinations identified. Using a training set of 91 stage I data sets, representing 61 individual samples, and an equivalent number of controls, an 11-analyte profile, composed of CA-125, CA 19-9, EGF-R, C-reactive protein, myoglobin, apolipoprotein A1, apolipoprotein CIII, MIP-1alpha, IL-6, IL-18 and tenascin C was identified and appears informative for all stages and common subtypes of ovarian cancer. Using a testing set of 245 samples, approximately twice the size of the model building set, the classifier had 91.3% sensitivity and 88.5% specificity. While these preliminary results are promising, further refinement and extensive validation of the classifier in a clinical trial is necessary to determine if the test has clinical value. CONCLUSIONS/SIGNIFICANCE: We describe a blood-based assay using 11 analytes that can distinguish women with ovarian cancer from those with benign conditions. Preliminary evaluation of the classifier suggests it has the potential to offer approximately 90% sensitivity and 90% specificity. While promising, the performance needs to be assessed in a blinded clinical validation study

Comprehensive Serum Profiling for the Discovery of Epithelial Ovarian Cancer Biomarkers

FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC = 0.933) and CA-125 (AUC = 0.907) were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800). To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912). Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the detection of ovarian cancer