Ranking of HMA Moisture Sensitivity Tests in Iowa, RB00-012, 2012

Several agencies specify AASHTO T283 as the primary test for field acceptance of moisture susceptibility in hot mix asphalt. When used in this application, logistical difficulties challenge its practicality, while repeatability is routinely scrutinized by contractors. An alternative test is needed which can effectively demonstrate the ability to screen mixtures based on expected performance. The ideal replacement can be validated with field performance, is repeatable, and allows for prompt reporting of results. Dynamic modulus, flow number, AASHTO T283, Hamburg wheel tracking device (HWTD), and the moisture induced sensitivity test (MIST) were performed on plant produced surface mixes in Iowa. Follow-up distress surveys were used to rank the mixes by their performance. The rankings indicate both the quantity of swelling from MIST conditioning and submersed flow number matched the performance ranking of all but one mixture. Hamburg testing parameters also appear effective, namely the stripping inflection point and the ratio between stripping slope and the creep slope. Dynamic modulus testing was ineffective, followed by AASHTO T283 and ratios produced from flow number results of conditioned samples.

Multiple Kernel Learning of Environmental Data. Case study: Analysis and Mapping of Wind Fields

The paper presents the Multiple Kernel Learning (MKL) approach as a modelling and data exploratory tool and applies it to the problem of wind speed mapping. Support Vector Regression (SVR) is used to predict spatial variations of the mean wind speed from terrain features (slopes, terrain curvature, directional derivatives) generated at different spatial scales. Multiple Kernel Learning is applied to learn kernels for individual features and thematic feature subsets, both in the context of feature selection and optimal parameters determination. An empirical study on real-life data confirms the usefulness of MKL as a tool that enhances the interpretability of data-driven models.

Development of Elispot and CFSE flow cytometric assays for detecting beryllium sensitivity

Background: Beryllium sensitization (BeS) is caused by exposure to beryllium in the workplace and may progress to chronic beryllium disease (CBD). This granulomatous lung disorder mimicks sarcoidosis clinically, but is characterized by beryllium specific CD4+ T-cells immune response. BeS is classically detected by beryllium lymphocyte proliferation test (BeLPT), but this assay requires radioactivity and is not very sensitive. In the context of a study aiming to evaluate if CBD patients are misdiagnosed as sarcoidosis patients in Switzerland, we developed EliSpot and CFSE beryllium flow cytometric test. Methods: 23 patients considered as having sarcoidosis (n = 21), CBD (n = 1) and possible CBD (n = 1) were enrolled. Elispot was performed using plate covered with gamma-IFN mAb. Cells were added to wells and incubated overnight at 37 °C with medium (neg ctrl), SEB (pos ctrl) or BeSO4 at 1, 10 and 100 microM. Anti-IFN-gamma biotinylated mAb were added and spots were visualized using streptavidinhorseradish peroxidase and AEC substrate reagent. Results were reported as spot forming unit (SFU). For Beryllium specific CFSE flow cytometry analysis, CFSE labelled cells were cultured in the presence of SEB and 1, 10 or 100 microM BeSO4. Unstimulated CFSE labeled cells were defined as controls. The cells were incubated for 6 days at 37 °C and 5% CO2. Surface labelling of T-lymphocytes and vivid as control of cells viability was performed at the time of harvest. Results: Using EliSpot technology, we were able to detect a BeS in 1/23 enrolled patients with a mean of 780 SFU (cut off value at 50 SFU). This positive result was confirmed using different concentration of BeSO4. Among the 23 patients tested, 22 showed negative results with EliSpot. Using CFSE flow cytometry, 1/7 tested patients showed a positive result with a beryllium specific CD4+ count around 30% versus 45% for SEB stimulation as positif control and 0.6 % for negative control. This patient was the one with a positive EliSpot assay. Conclusions: The preliminary data demonstrated the feasibility of Elispot and CFSE flow cytometry to detect BeS. The patient with a beryllium specific positive EliSpot and CFSE flow cytometry result had been exposed to beryllium at her workplace 20 years ago and is still regularly controlled for her pulmonary status. A positive BeLPT had already been described in 2001 in France for this patient. Further validation of these techniques are in progress.

Relation between high-sensitivity C-reactive protein and cardiovascular and renal markers in a middle-income country in the African region.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is associated with several cardiovascular risk factors (CVRF) and with renal function markers. However, these associations have not been examined in populations in the African region. We analyzed the distribution of hs-CRP and the relationship with a broad set of CVRF, renal markers and carotid intima-media thickness (IMT), in the Seychelles (African region). METHODS: We conducted a survey in the population aged 25-64years (n=1255, participation rate: 80.2%). Analyses were restricted to persons of predominantly African descent (n=1011). RESULTS: Mean and median hs-CRP serum concentrations (mg/l) were 3.1 (SD 7.6) and 1.4 (IQR 0.7-2.9) in men and 4.5 (SD 6.7) and 2.2 (IQR 1.0-5.4) in women (p<0.001 for difference between men and women). hs-CRP was significantly associated with several conventional CVRF, and particularly strongly with markers of adiposity. With regards to renal markers, hs-CRP was strongly associated with cystatin C and with microalbuminuria but not with creatinine. hs-CRP was not associated with IMT. CONCLUSIONS: Serum concentration of hs-CRP was significantly associated with sex, several CVRF and selected renal function markers, which extends similar findings in Europe and in North America to a population in the African region. These findings can contribute to guide recommendations for the use of hs-CRP in clinical practice in the region.

Factor structure of early smoking experiences and associations with smoking behavior: valence or sensitivity model?

The Early Smoking Experience (ESE) questionnaire is the most widely used questionnaire to assess initial subjective experiences of cigarette smoking. However, its factor structure is not clearly defined and can be perceived from two main standpoints: valence, or positive and negative experiences, and sensitivity to nicotine. This article explores the ESE's factor structure and determines which standpoint was more relevant. It compares two groups of young Swiss men (German- and French-speaking). We examined baseline data on 3,368 tobacco users from a representative sample in the ongoing Cohort Study on Substance Use Risk Factors (C-SURF). ESE, continued tobacco use, weekly smoking and nicotine dependence were assessed. Exploratory structural equation modeling (ESEM) and structural equation modeling (SEM) were performed. ESEM clearly distinguished positive experiences from negative experiences, but negative experiences were divided in experiences related to dizziness and experiences related to irritations. SEM underlined the reinforcing effects of positive experiences, but also of experiences related to dizziness on nicotine dependence and weekly smoking. The best ESE structure for predictive accuracy of experiences on smoking behavior was a compromise between the valence and sensitivity standpoints, which showed clinical relevance.

Antigen binding to secretory immunoglobulin A results in decreased sensitivity to intestinal proteases and increased binding to cellular Fc receptors.

In intestinal secretions, secretory IgA (SIgA) plays an important sentinel and protective role in the recognition and clearance of enteric pathogens. In addition to serving as a first line of defense, SIgA and SIgA x antigen immune complexes are selectively transported across Peyer's patches to underlying dendritic cells in the mucosa-associated lymphoid tissue, contributing to immune surveillance and immunomodulation. To explain the unexpected transport of immune complexes in face of the large excess of free SIgA in secretions, we postulated that SIgA experiences structural modifications upon antigen binding. To address this issue, we associated specific polymeric IgA and SIgA with antigens of various sizes and complexity (protein toxin, virus, bacterium). Compared with free antibody, we found modified sensitivity of the three antigens assayed after exposure to proteases from intestinal washes. Antigen binding further impacted on the immunoreactivity toward polyclonal antisera specific for the heavy and light chains of the antibody, as a function of the antigen size. These conformational changes promoted binding of the SIgA-based immune complex compared with the free antibody to cellular receptors (Fc alphaRI and polymeric immunoglobulin receptor) expressed on the surface of premyelocytic and epithelial cell lines. These data reveal that antigen recognition by SIgA triggers structural changes that confer to the antibody enhanced receptor binding properties. This identifies immune complexes as particular structural entities integrating the presence of bound antigens and adds to the known function of immune exclusion and mucus anchoring by SIgA.

The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression.

The 24-item Brief Psychiatric Rating Scale (BPRS, version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Colorectal cancer metastasis: the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation.

PURPOSE: To assess the usefulness of combining hyperthermia with a DNA repair inhibitor (double-strand break bait [Dbait]) and its potential application to radiofrequency ablation (RFA) in a preclinical model of human colorectal cancer. MATERIALS AND METHODS: The local ethics committee of animal experimentation approved all investigations. First, the relevance was assessed by studying the survival of four human colorectal adenocarcinoma cell cultures after 1 hour of hyperthermia at 41°C or 43°C with or without Dbait. Human colon adenocarcinoma cells (HT-29) were grafted subcutaneously into nude mice (n = 111). When tumors reached approximately 500 mm(3), mice were treated with Dbait alone (n = 20), sublethal RFA (n = 21), three different Dbait schemes and sublethal RFA (n = 52), or a sham treatment (n = 18). RFA was performed to ablate the tumor center alone. To elucidate antitumor mechanisms, 39 mice were sacrificed for blinded pathologic analysis, including assessment of DNA damage, cell proliferation, and tumor necrosis. Others were monitored for tumor growth and survival. Analyses of variance and log-rank tests were used to evaluate differences. RESULTS: When associated with mild hyperthermia, Dbait induced cytotoxicity in all tested colon cancer cell lines. Sublethal RFA or Dbait treatment alone moderately improved survival (median, 40 days vs 28 days for control; P = .0005) but combination treatment significantly improved survival (median, 84 days vs 40 days for RFA alone, P = .0004), with approximately half of the animals showing complete tumor responses. Pathologic studies showed that the Dbait and RFA combination strongly enhances DNA damage and coagulation areas in tumors. CONCLUSION: Combining Dbait with RFA sensitizes the tumor periphery to mild hyperthermia and increases RFA antitumor efficacy.

Sensitivity to Change of the Ultrasound synovitis SONAR Score in RA Patients: Results of the Scqm Cohort

Background/Purpose: Since the end of 2009, an ultrasound scoring call SONAR has been implemented for RA patients as a routine tool in the SCQM registry (Swiss Clinical Quality Management registry for rheumatic diseases). A cross-sectional evaluation of patients with active disease and clinical remission according to the DAS28ESR and the novel ACR/EULAR remission criteria from 2010 clearly indicated a good correlational external validity of synovial pathologies with clinical disease activity in RA (2012 EULAR meeting. Objective: of this study was to evaluate the sensitivity to change of B-mode and Power-Doppler scores in a longitudinal perspective along with the changes in DAS28ESR in two consecutive visits among the patients included in the SCQM registry Methods: All patients who had at least two SONAR scores and simultaneous DAS28ESR evaluations between December 2009 and June 2012 were included in this study. The data came from 20 different operators working mostly in hospitals but also in private practices, who had received a previous teaching over 3 days in a reference center. The SONAR score includes a semi-quantitative B mode and Power-Doppler evaluation of 22 joints from 0 to 3, maximum 66 points for each score. The selection of these 22 joints was done in analogy to a 28 joint count and further restricted to joint regions with published standard ultrasound images. Both elbows and wrist joints were dynamically scanned from the dorsal and the knee joints from a longitudinal suprapatellar view in flexion and in joint extension. The bilateral evaluation of the second to fifth metacarpophalangeal and proximal interphalangeal joints was done from a palmar view in full extension, and the Power-Doppler scoring from a dorsal view with hand and finger position in best relaxation. Results: From the 657 RA patients with at least one score performed, 128 RA patients with 2 or more consultations of DAS28ESR, and a complete SONAR data set could be included. The mean (SD) time between the two evaluations was 9.6 months (54). The mean (SD) DAS28ESR was: 3.5 (1.3) at the first visit and was significantly lower (mean 3.0, SD.2.0, p:_0.0001) at the second visit. The mean (SD) of the total B mode was 12 (9.5) at baseline and 9.6 (7.6) at follow-up (p_0.0004). The Power-Doppler score at entry was 2.9 (5.7) and 1.9 (3.6), at the second visit, p _0.0001. The Pearson r correlation between change in DAS28ESR and the B mode was 0.44 (95% CI: 0.29, 0.57, p_ 0.0001),and 0.35 (95% CI: 0.16, 0.50, p _ 0.0002) for the Power-Doppler score,. Clinical relevant change in DAS (_1.1) was associated with a change of total B mode score _3 in 23/32 patients and a change a Doppler score _0.5 in 19/26. Conclusion: This study confirms that the SONAR score is sensitive to change and provides a complementary method of assessing RA disease activity to the DAS that could be very useful in daily practice.

Kernel-based Mapping of Meteorological Fields in Complex Orography

Due to the advances in sensor networks and remote sensing technologies, the acquisition and storage rates of meteorological and climatological data increases every day and ask for novel and efficient processing algorithms. A fundamental problem of data analysis and modeling is the spatial prediction of meteorological variables in complex orography, which serves among others to extended climatological analyses, for the assimilation of data into numerical weather prediction models, for preparing inputs to hydrological models and for real time monitoring and short-term forecasting of weather.In this thesis, a new framework for spatial estimation is proposed by taking advantage of a class of algorithms emerging from the statistical learning theory. Nonparametric kernel-based methods for nonlinear data classification, regression and target detection, known as support vector machines (SVM), are adapted for mapping of meteorological variables in complex orography.With the advent of high resolution digital elevation models, the field of spatial prediction met new horizons. In fact, by exploiting image processing tools along with physical heuristics, an incredible number of terrain features which account for the topographic conditions at multiple spatial scales can be extracted. Such features are highly relevant for the mapping of meteorological variables because they control a considerable part of the spatial variability of meteorological fields in the complex Alpine orography. For instance, patterns of orographic rainfall, wind speed and cold air pools are known to be correlated with particular terrain forms, e.g. convex/concave surfaces and upwind sides of mountain slopes.Kernel-based methods are employed to learn the nonlinear statistical dependence which links the multidimensional space of geographical and topographic explanatory variables to the variable of interest, that is the wind speed as measured at the weather stations or the occurrence of orographic rainfall patterns as extracted from sequences of radar images. Compared to low dimensional models integrating only the geographical coordinates, the proposed framework opens a way to regionalize meteorological variables which are multidimensional in nature and rarely show spatial auto-correlation in the original space making the use of classical geostatistics tangled.The challenges which are explored during the thesis are manifolds. First, the complexity of models is optimized to impose appropriate smoothness properties and reduce the impact of noisy measurements. Secondly, a multiple kernel extension of SVM is considered to select the multiscale features which explain most of the spatial variability of wind speed. Then, SVM target detection methods are implemented to describe the orographic conditions which cause persistent and stationary rainfall patterns. Finally, the optimal splitting of the data is studied to estimate realistic performances and confidence intervals characterizing the uncertainty of predictions.The resulting maps of average wind speeds find applications within renewable resources assessment and opens a route to decrease the temporal scale of analysis to meet hydrological requirements. Furthermore, the maps depicting the susceptibility to orographic rainfall enhancement can be used to improve current radar-based quantitative precipitation estimation and forecasting systems and to generate stochastic ensembles of precipitation fields conditioned upon the orography.

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans.

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.

Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants.

In a multicenter study a new, fully automated Roche Diagnostics Elecsys HBsAg II screening assay with improved sensitivity to HBsAg mutant detection was compared to well-established HBsAg tests: AxSYM HBsAg V2 (Abbott), Architect HBsAg (Abbott), Advia Centaur HBsAg (Bayer) Enzygnost HBsAg 5.0 (Dade-Behring), and Vitros Eci HBsAg (Ortho). A total of 16 seroconversion panels, samples of 60 HBsAg native mutants, and 31 HBsAg recombinant mutants, dilution series of NIBSC and PEI standards, 156 HBV positive samples comprising genotypes A to G, 686 preselected HBsAg positive samples from different stages of infection, 3,593 samples from daily routine, and 6,360 unselected blood donations were tested to evaluate the analytical and clinical sensitivity, the detection of mutants, and the specificity of the new assay. Elecsys HBsAg II showed a statistically significant better sensitivity in seroconversion panels to the compared tests. Fifty-seven out of 60 native mutants and all recombinant mutants were found positive. Among 156 HBV samples with different genotypes and 696 preselected HBsAg positive samples Elecsys HBsAg II achieved a sensitivity of 100%. The lower detection limit for NIBSC standard was calculated to be 0.025 IU/ml and for the PEI standards ad and ay it was <0.001 and <0.005 U/ml, respectively. Within 2,724 daily routine specimens and 6.360 unselected blood donations Elecsys HBsAg II showed a specificity of 99.97 and 99.88%, respectively. In conclusion the new Elecsys HBsAg II shows a high sensitivity for the detection of all stages of HBV infection and HBsAg mutants paired together with a high specificity in blood donors, daily routine samples, and potentially interfering sera.