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".

ALK inhibitors in the treatment of advanced NSCLC.

Pharmacologic agents that target protein products of oncogenes in tumors are playing an increasing clinical role in the treatment of cancer. Currently, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent the standard of care for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. Subsequently other genetic abnormalities with "driver" characteristics - implying transforming and tumor maintenance capabilities have been extensively reported in several small distinct subsets of NSCLC. Among these rare genetic changes, anaplastic lymphoma kinase (ALK) gene rearrangements, most often consisting in a chromosome 2 inversion leading to a fusion with the echinoderm microtubule-associated protein like 4 (EML4) gene, results in the abnormal expression and activation of this tyrosine kinase in the cytoplasm of cancer cells. This rearrangement occurs in 2-5% of NSCLC, predominantly in young (50 years or younger), never- or former-smokers with adenocarcinoma. This aberration most commonly occurs a independently of EGFR and KRAS gene mutations. A fluorescent in situ hybridization assay was approved by the US Food and Drug Administration (FDA) as the standard method for the detection of ALK gene rearrangement in clinical practice and is considered the gold standard. Crizotinib, a first-in-class dual ALK and c-MET inhibitor, has been shown to be particularly effective against ALK positive NSCLC, showing dramatic and prolonged responses with low toxicity, predominantly restricted to the gastro-intestinal and visual systems, and generally self-limiting or easily managed. However, resistance to crizotinib inevitably emerges. The molecular mechanisms of resistance are currently under investigation, as are therapeutic approaches including crizotinib-based combination therapy and novel agents such as Hsp90 inhibitors. This review aims to present the current knowledge on this fusion gene, the clinic-pathological profile of ALK rearranged NSCLC, and to review the existing literature on ALK inhibitors, focusing on their role in the treatment of NSCLC.

Remote Sensing (LIDAR) for Management of Highway Assets for Safety, 2003

The main objective of this study was to utilize light detection and ranging (LIDAR) technology to obtain highway safety-related information. The safety needs of older drivers in terms of prolonged reaction times were taken into consideration. The tasks undertaken in this study were (1) identification of crashes that older drivers are more likely to be involved in, (2) identification of highway geometric features that are important in such crashes, (3) utilization of LIDAR data for obtaining information on the identified highway geometric features, and (4) assessment of the feasibility of using LIDAR data for such applications. A review of previous research indicated that older drivers have difficulty negotiating intersections, and it was recognized that intersection sight triangles were critical to safe intersection negotiation. LIDAR data were utilized to obtain information on potential sight distance obstructions at six selected intersections located on the Iowa Highway 1 corridor by conducting in-office line-of-sight analysis. Crash frequency, older driver involvement, and data availability were considerations in the selection of the six intersections. Results of the in-office analysis were then validated by visiting the intersections in the field. Sixty-six potential sight distance obstructions were identified by the line-of-sight analysis, out of which 62 (89.8%) were confirmed while four (5.8%) were not confirmed by the video. At least three (4.4%) potential sight distance obstructions were discovered in the video that were not detected by the line-of-sight analysis. The intersection with the highest crash frequency involving older drivers was correctly found to have obstructions located within the intersection sight triangles. Based on research results, it is concluded that LIDAR data can be utilized for identifying potential sight distance obstructions at intersections. The safety of older drivers can be enhanced by locating and rectifying intersections with obstructions in sight triangles.

Road Safety Audit Report for US 61 from the ECL of Muscatine to the WCL of, 2008

U.S. Highway 61 between Muscatine and Davenport, Iowa, is a four-lane divided section of road approximately 21 miles in length. This section was found to be among the top 5% of Iowa roadways for single-vehicle run-off-road, impaired driver, unbelted driver, and speed-related crashes for the period of 2001 through 2005. A road safety audit of this corridor was deemed appropriate by the Iowa Department of Transportation’s Office of Traffic and Safety. Staff and officials from the Iowa Department of Transportation (Iowa DOT), Iowa State Patrol, Governor’s Traffic Safety Bureau, Federal Highway Administration, Center for Transportation Research and Education, and several local law enforcement and transportation agencies met to review crash data and discuss potential safety improvements to US 61. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this US 61 corridor and explains several selected mitigation strategies.

Evolució i anàlisi del metabolisme ambiental del polígon industrial. El cas de Maó (Menorca)

El polígon industrial de Maó, POIMA, és un dels principals motors econòmics de l’illa de Menorca. La Universitat Autònoma de Barcelona (UAB) en col·laboració amb l’Observatori Socioambiental de Menorca (OBSAM), ha fet un projecte d’anàlisi de l’evolució històrica i del metabolisme actual del polígon. L’estudi es centra en 5 vectors; usos del sòl, energètic, hídric, materials i mobilitat dels quals les dades han estat obtingudes a partir d’enquestes, entrevistes a les empreses i observacions directes semi-quantitatives. Com a resultat es presenten diverses propostes de millora per augmentar l’eficiència de POIMA, analitzant el potencial d’autosuficiència energètic i hídric, reduint l’impacte ambiental i reutilitzant els residus com a recursos entre empreses, sinèrgies.

Synthesis of Traffic Calming Techniques in Work Zones, 2009

Nationwide, over 1,000 fatalities and 40,000 injuries occur annually in work zones, which include both construction zones and areas where maintenance is performed. The majority (85%) of work zone accidents result from unsafe driver behavior, and vehicle speed is often a factor in work zone crashes. In order to address speed and driver behavior near work zones, roadway agencies have developed different traffic calming measures. The objective of this research is to summarize the effectiveness of different traffic calming treatments for reducing speeds in work zones. This project 1. identified work zone traffic calming treatments for which information has not been well summarized, 2. identified state of the art and new technologies for work zone traffic calming, and 3. synthesized research related to items 1 and 2

Disentangling water usage in the European Union: A decomposition analysis

The Water Framework Directive (WFD) defines common objectives for water resources throughout the European Union (EU). Given this general approach to water preservation and water policy, the objective of this paper is to analyse whether common patterns of water consumption exist within Europe. In particular, our study uses two methods to reveal the reasons behind sectoral water use in all EU countries. The first method is based on an accounting indicator that calculates the water intensity of an economy as the sum of sectoral water intensities. The second method is a subsystem input‐output model that divides total water use into different income channels within the production system. The application uses data for the years 2005 and 2009 on water consumption in the production system of the 27 countries of the EU. From our analysis it emerges that EU countries are characterized by very different patterns of water consumption. In particular water consumption by the agriculture sector is extremely high in Central/Eastern Europe, relative to the rest of Europe. In most countries, the water used by the fuel, power and water sector is consumed to satisfy domestic final demand. However, our analysis shows that for some countries exports from this sector are an important driver of water consumption. Focusing on the agricultural sector, the decomposition analysis suggests that water usage in Mediterranean countries is mainly driven by final demand for, and exports of, agricultural products. In Central/Eastern Europe domestic final demand is the main driver of water consumption, but in this region the proportion of water use driven by demand for exports is increasing over time. Given these heterogeneous water consumption patterns, our analysis suggests that Mediterranean and Central/Eastern European countries should adopt specific water policies in order to achieve efficient levels of water consumption in the European Union. JEL codes: N5; C67 Keywords: Water use, Subsystem input–output model; Water intensity, European Union.

Assessment of Channelizing Device Effectiveness on High Speed/High Volume Roadways, 2007

Part 6 of the Manual on Uniform Traffic Control Devices (MUTCD) describes several types of channelizing devices that can be used to warn road users and guide them through work zones; these devices include cones, tubular markers, vertical panels, drums, barricades, and temporary raised islands. On higher speed/volume roadways, drums and/or vertical panels have been popular choices in many states, due to their formidable appearance and the enhanced visibility they provide when compared to standard cones. However, due to their larger size, drums also require more effort and storage space to transport, deploy and retrieve. Recent editions of the MUTCD have introduced new devices for channelizing; specifically of interest for this study is a taller (>36 inches) but thinner cone. While this new device does not offer a comparable target value to that of drums, the new devices are significantly larger than standard cones and they offer improved stability as well. In addition, these devices are more easily deployed and stored than drums and they cost less. Further, for applications previously using both drums and tall cones, the use of tall cones only provides the ability for delivery and setup by a single vehicle. An investigation of the effectiveness of the new channelizing devices provides a reference for states to use in selecting appropriate traffic control for high speed, high volume applications, especially for short term or limited duration exposures. This study includes a synthesis of common practices by state DOTs, as well as daytime and nighttime field observations of driver reactions using video detection equipment. The results of this study are promising for the day and night performance of the new tall cones, comparing favorably to the performance of drums when used for channelizing in tapers. The evaluation showed no statistical difference in merge distance and location, shy distance, or operating speed in either daytime or nighttime conditions. The study should provide a valuable resource for state DOTs to utilize in selecting the most effective channelizing device for use on high speed/high volume roadways where timely merging by drivers is critical to safety and mobility.

The Effect of the No-Passing Zone Sign on "Passing" Accidents, 1963

The No Passing Zone sign (Wl0-4) was designed in 1958 for the purpose of informing the driver contemplating a passing maneuver of hazardous sight conditions ahead. This warning sign, of pennent shape design, was placed on the left side of the road so as to be more conspicuous to the intended driver. During the two year period 1959-1960, the Wl0-4 signs were erected throughout the Iowa Primary Road System.

Iowa Study of No Passing Zone Signing, 1962

This report is compiled from data gathered by interviewing motorists to sample their opinion of Iowa's method of supplementing the yellow barrier line pavement marking of no passing zones on primary highways with yellow pennant shaped "No Passing Zone" signs mounted on the left shoulder of the highway. The effective designation of no passing zones is one form of control that can contribute to a reduction in the number of fatal high-speed head-on collisions resulting from passing in areas which do not afford sufficient sight distance of approaching traffic. It is the purpose of this report to present an evaluation of the Iowa "No Passing Zone" sign by individuals from all states who have traveled on Iowa's primary highways and who must obey the no passing zone restrictions and be warned by this sign of the presence of the zones. The "No Passing Zone" sign was formulated and approved by the Governor's Safety Committee a short time prior to the experimental erection of the signs. The Governor's Safety Committee adopted this sign as they felt that such a sign should be distinctive (not similar to any other type of sign) and easily visible to a driver attempting a passing maneuver.

Work Zone Simulation Model, 1999

To support the analysis of driver behavior at rural freeway work zone lane closure merge points, Center for Transportation Research and Education staff collected traffic data at merge areas using video image processing technology. The collection of data and the calculation of the capacity of lane closures are reported in a companion report, "Traffic Management Strategies for Merge Areas in Rural Interstate Work Zones". These data are used in the work reported in this document and are used to calibrate a microscopic simulation model of a typical, Iowa rural freeway lane closure. The model developed is a high fidelity computer simulation with an animation interface. It simulates traffic operations at a work zone lane closure. This model enables traffic engineers to visually demonstrate the forecasted delay that is likely to result when freeway reconstruction makes it necessary to close freeway lanes. Further, the model is also sensitive to variations in driver behavior and is used to test the impact of slow moving vehicles and other driver behaviors. This report consists of two parts. The first part describes the development of the work zone simulation model. The simulation analysis is calibrated and verified through data collected at a work zone in Interstate Highway 80 in Scott County, Iowa. The second part is a user's manual for the simulation model, which is provided to assist users with its set up and operation. No prior computer programming skills are required to use the simulation model.

Traffic Management Strategies for Merge Area in Rural Interstate Work Zones, CTRE 97-12, 1999

The Iowa Department of Transportation, like many other state transportation agencies, is experiencing growing congestion and traffic delays in work zones on rural interstate highways. The congestion results in unproductive and wasteful delays for both motorists and commercial vehicles. It also results in hazardous conditions where vehicle stopped in queues on rural interstate highways are being approached by vehicles upstream at very high speeds. The delays also result in driver frustration, making some drivers willing to take unsafe risks in an effort to bypass delays. To reduce the safety hazards and unproductive delays of congested rural interstate work zones, the Iowa Department of Transportation would like to improve its traffic management strategies at these locations. Applying better management practices requires knowledge of the traffic flow properties and driver behavior in and around work zones, and knowledge of possible management strategies. The project reported here and in a companion report documents research which seeks to better understand traffic flow behavior at rural interstate highway work zones and to estimate the traffic carrying capacity of work zone lane closures. In addition, this document also reports on technology available to better manage traffic in and around work zones.

Intercity Passenger Carrier Improvement Study, Final Report, 1977

The goal of this research was to recommend specific changes relating to service by intercity buses and third level air carriers to propose an appropriate state role in the implementation of changes. Changes contemplated in this research were to be directed to the increased use of intercity buses and third level air carriers in such manner as to exert a benefit to user as well as the general public. Specific objectives of the project included: (1) to analyze the potential for a system of express intercity bus routes in Iowa; (2) to estimate the demand for third level air carrier services in cities having populations under 50,000; (3) to forecast the relationship between economic costs and benefits from an intercity bus system emphasizing express routes between major population centers and supporting a subsystem of local and intraregional public transportation; (4) to estimate the economic feasibility of expanded third level air carrier service with emphasis upon those routes proposed as worth of further evaluation; and (5) to provide guidance for establishing the need for state and local subsidies to institute a system of express intercity buses and to expand third level air carrier services. In addition to passenger movements, enhancing package freight shipments was also to be considered in the evaluation of proposed improvements.

Transit Assistance Program for Iowa, 1975

This inventory of transit services in Iowa covers urban transit, intercity passenger bus carriers and charter operators, taxicab operations, rural transit services and special services, and includes the results of questionnaire and interview surveys, and the resulting recommendations. The recommendations urge a centralized source of data and expertise, a public information program, the utilization of federal aid, the continuance of existing transit services with no dimunition of service level, the establishment of new services in communities of over 20,000 population, the sponsorship of demonstrations in communities with populations of 10,000 to 20,000, and the development and improvement of rural transit service. Based on state and local community experience, recommendations are made concerning revenue sources to support transit in Iowa, and four alternative state transit assistance programs are presented.

Trends in dietary intake in Switzerland, 1999 to 2009.

OBJECTIVE: To assess nutrition trends of the Geneva population for the period 1999-2009. DESIGN: Bus Santé Geneva study, which conducts annual health surveys in random samples of the Geneva population. Dietary intake was assessed using a validated FFQ and trends were assessed by linear regression. SETTING: Population-based survey. SUBJECTS: Data from 9283 participants (50% women, mean age 51·5 (sd 10·8) years) were analysed. RESULTS: In both genders total energy intake decreased from 1999 to 2009, by 2·9% in men and by 6·3% in women (both trends P < 0·005). Vegetable protein and total carbohydrate intakes, expressed as a percentage of total energy intake, increased in women. MUFA intake increased while SFA, PUFA and alcohol intakes decreased in both genders. Intakes of Ca, Fe and carotene decreased in both genders. No changes in fibre, vitamin D and vitamin A intakes were found. Similar findings were obtained after excluding participants with extreme dietary intakes, except that the decreases in SFA, vegetable protein and carbohydrate were no longer significant in women. CONCLUSIONS: Between 1999 and 2009, a small decrease in total energy intake was noted in the Geneva population. Although the decrease in alcohol and SFA intakes is of interest, the decrease in Ca and Fe intakes may have adverse health effects in the future.