Development of Non-Petroleum Based Binders for Use in Flexible Pavements, TR-594, 2010

Most bituminous adhesives or binders that are used for pavement materials are derived primarily from fossil fuels. With petroleum oil reserves becoming depleted and the drive to establish a bio-based economy, there is a push to produce binders from alternative sources, particularly from biorenewable resources. However, until now, no research has studied the applicability of utilizing bio-oils as a bitumen replacement (100% replacement) in the pavement industry. The main objective of this research was to test various properties of bio-oils in order to determine the applicability of using bio-oils as binders in the pavement industry. The overall conclusions about the applicability of using bio-oils as bio-binders in the pavement industry can be summarized as follows: 1. Bio-oils cannot be used as bio-binders/pavement materials without any heat pre-treatment/upgrading procedure. 2. Current testing standards and specifications, especially Superpave procedures, should be modified to comply with the properties of bio-binders. 3. The temperature range of the viscous behavior for bio-oils may be lower than that of bitumen binders by about 30°–40° C. 4. The rheological properties of the unmodified bio-binders vary in comparison to bitumen binders, but the rheological properties of these modified bio-binders change significantly upon adding polymer modifiers. 5. The high-temperature performance grade for the developed bio-binders may not vary significantly from that of the bitumen binders, but the low-temperature performance grade may vary significantly

Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals.

BACKGROUND: We investigated changes in biomarkers of liver disease in HIV-HCV-coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV infection and to HIV-monoinfected individuals. METHODS: Non-invasive biomarkers of liver disease (hyaluronic acid [HYA], aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 [FIB-4] index and cytokeratin-18 [CK-18]) were correlated with liver histology in 49 HIV-HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV-HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on cART. All analyses were conducted before starting HCV treatment. RESULTS: Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR stage (P<0.002 for all comparisons). The mean ±sd area under the receiver operating characteristic (AUROC) curve values for advanced fibrosis (≥F3 METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86 ±0.05, 0.84 ±0.08, 0.80 ±0.09 and 0.81 ±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV-HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, respectively; P=0.1), mainly due to the reversion of HIV-induced thrombocytopaenia, whereas HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed <3% during untreated HIV-infection. Overall, 3 patients died from end-stage liver disease, and 10 from other causes. CONCLUSIONS: Biomarkers of liver disease highly correlated with fibrosis in HIV-HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV-HCV-coinfected individuals, at least during successful cART.

How do Swiss Gastroenterologists assess Activity of Inflammatory Bowel Disease in Daily Practice: by Clinical Indices, Endoscopic Activity, or Biomarkers?

Background a nd A ims: There is a n ongoing d ebate which i sthe most appropriate w ay t o measure inflammatory boweldisease (IBD) activity (be it b y clinical i ndices, e ndoscopy, orbiomarkers). Accumulating evidence associates m ucosalhealing with a reduction in I BD-related s urgery andhospitalizations. We a imed to i nvestigate which outcomeparameters are used in daily practice for IBD monitoring.Methods: A q uestionnaire was sent in J uly 2010 t o all boardcertified gastroenterologists in S witzerland to evaluate t heassessment strategy of IBD activity, t he items on whichtherapeutic decisions w ere based upon, and the kind ofbiomarkers used for monitoring IBD activity.Results: Response rate was 57% (153/270). Mean physician'sage was 5 0±9years, mean duration o f gastroenterologicpractice 1 4±8years, 52% of them were working in p rivatepractice a nd 48% in h ospitals. S eventy-eight percent usedclinical activity i ndices as g old standard for IBD activityassessment, followed by 15% choosing endoscopic activity, and7% favouring biomarkers. Gastroenterologists based theirtherapeutic decisions in 70% on clinical activity indices, 24% onendoscopic activity, a nd 6% o n biomarkers. Most frequentlyused biomarkers were C-reactive protein (94%), complete bloodcount (78%) and fecal calprotectin (74%).Conclusions: I n daily p ractice, most IBD patients a remonitored based u pon t heir clinical a ctivity. B iomarkers a reperceived as l ess important compared to clinical andendoscopic activity. S imilar to activity a ssessment, alsotherapeutic decisions a re mostly made on the basis of clinicalactivity indices. The upcoming scientific evidence on the impactof mucosal h ealing does n ot yet seem to influence the dailypractice of gastroenterologists.

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained.The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

Cerebrospinal fluid soluble amyloid-β protein precursor as a potential novel biomarkers of Alzheimer's disease.

In this report, we confirm our previous findings of increased concentrations of soluble amyloid-β protein precursor (sAβPP) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large cohort of patients (n = 314), not overlapping with those of our previous study, and we extend our observations by including a control group of participants with normal cognition. In addition, we investigate the effects of age, the APOEε4 genotype, and the blood-CSF barrier function on the concentrations of sAβPPα and sAβPPβ. The study participants were categorized according to clinical-neuropsychological criteria, supported by CSF neurochemical dementia diagnostics (NDD) analyses. sAβPPα concentrations in the AD group (132.0 ± 44.8) were significantly higher than in the control group (105.3 ± 37.3, p < 0.0005) but did not differ from the MCI-AD group (138.5 ± 39.5, p = 0.91). The MCI-AD group differed significantly from the MCI-O (97.3 ± 34.3, p < 0.05) group. There was no difference between the control and the MCI-O groups (p = 0.94). Similarly, sAβPPβ concentrations in the AD group (160.2 ± 54.3) were significantly higher than in the control group (129.9 ± 44.6, p < 0.005) but did not differ from the MCI-AD group (184.0 ± 56.4, p = 0.20). The MCI-AD group differed significantly from the MCI-O (127.8 ± 46.2, p < 0.05) group. There was no difference between the control and the MCI-O groups (p > 0.99). We observed highly significant correlation of the two sAβPP forms. Age and the CSF-serum albumin ratio were significant albeit weak predictors of the sAβPPα and sAβPPβ concentrations, while carrying the APOEε4 allele did not influenced the levels of the sAβPP forms. Taken together, the results strongly suggest that CSF sAβPP concentrations may be considered as an extension of already available NDD tools.

Audit report on the Iowa Petroleum Underground Storage Tank Board (UST Board) for the year ended June 30, 2014

Audit report on the Iowa Petroleum Underground Storage Tank Board (UST Board) for the year ended June 30, 2014

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Bimodal size distributions were generally observed (5 μm and <1 μm). Surface characteristics of PM4 varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly (p<0.05) during two consecutive days of exposure for non-smoker workers. On the other hand, no statistically significant differences were observed for serum levels of hexanal, nonanal and 4- hydroxy-nonenal (p>0.05). Biomarkers levels will be compared to exposure variables to gain a better understanding of the relation between the particulate characteristics and the formation of ROS by-products. This project is financed by the Swiss State Secretariat for Education and Research. It is conducted within the framework of the COST Action 633 "Particulate Matter - Properties Related to Health Effects".

Development of Non-Petroleum-Based Binders for Use in Flexible Pavements – Phase II, TR-650, 2015

Bio-binders can be utilized as asphalt modifiers, extenders, and replacements for conventional asphalt in bituminous binders. From the rheology results of Phase I of this project, it was found that the bio-binders tested had good performance, similar to conventional asphalt, except at low temperatures. Phase II of this project addresses this shortcoming and evaluates the Superpave performance of laboratory mixes produced with the enhanced bio-binders. The main objective of this research was to develop a bio-binder capable of replacing conventional asphalt in flexible pavements by incorporating ground tire rubber (GTR) into bio-oil derived from fast pyrolysis of agriculture and forestry residues. The chemical compatibility of the new bio-binder with GTR was assessed, and the low-temperature performance of the bio-binders was enhanced by the use of GTR. The newly developed binder, which consisted of 80 percent conventional binder and 20 percent rubber-modified bio-oil (85 percent bio-oil with 15 percent GTR), was used to produce mixes at two different air void contents, 4 and 7 percent. The laboratory performance test results showed that the performance of the newly developed bio-binder mixes is as good as or better than conventional asphalt mixes for fatigue cracking, rutting resistance, moisture sensitivity, and low-temperature cracking. These results need to be validated in field projects in order to demonstrate adequate performance for this innovative and sustainable technology for flexible pavements.

Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations?

Since 2004, four antiangiogenic drugs have been approved for clinical use in patients with advanced solid cancers, on the basis of their capacity to improve survival in phase III clinical studies. These achievements validated the concept introduced by Judah Folkman that the inhibition of tumor angiogenesis could control tumor growth. It has been suggested that biomarkers of angiogenesis would greatly facilitate the clinical development of antiangiogenic therapies. For these four drugs, the pharmacodynamic effects observed in early clinical studies were important to corroborate activities, but were not essential for the continuation of clinical development and approval. Furthermore, no validated biomarkers of angiogenesis or antiangiogenesis are available for routine clinical use. Thus, the quest for biomarkers of angiogenesis and their successful use in the development of antiangiogenic therapies are challenges in clinical oncology and translational cancer research. We review critical points resulting from the successful clinical trials, review current biomarkers, and discuss their potential impact on improving the clinical use of available antiangiogenic drugs and the development of new ones.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease.

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Biomarkers for the assessment of chlorpyrifos effects on earthworms and on soil functional parameters

The objective of this work was to evaluate the effects of chlorpyrifos on earthworms and on soil functional parameters. An integrated laboratory-field study was performed in a wheat field in Argentina, sprayed with chlorpyrifos at two recommended application rates (240 or 960 g ha-1 style='vertical-align:baseline'> a.i.). Laboratory tests included neutral red retention time, comet assay (single cell gel electrophoresis), and avoidance behavior, each using the earthworm Eisenia andrei exposed in soil collected 1 or 14 days after pesticide application, and the bait-lamina test. Field tests assessed organic matter breakdown using the litterbag and bait-lamina assays. Earthworm populations in the field were assessed using formalin application and hand-sorting. The neutral red retention time and comet assays were sensitive biomarkers to the effects of chlorpyrifos on the earthworm E. andrei; however, the earthworm avoidance test was not sufficiently robust to assess these effects. Feeding activity of soil biota, assessed by the bait lamina test, was significantly inhibited by chlorpyrifos after 97 days, but recovered by the 118th day of the test. Litterbag test showed no significant differences in comparison to controls. Earthworm abundance in the field was too low to adequately test the sensitivity of this assessment endpoint.

Letter health consultation : Olin former petroleum bulk plant, Olin, Jones County, Iowa (2010)

This letter has been prepared as a consultation to evaluate human health impacts from residue contamination left from the operation of a bulk plant located in Olin, Iowa. The Iowa Department of Public Health’s priority is to ensure the Olin community has the best information possible to safeguard its health. That information is included in following paragraphs.

Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.

A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data.