963 resultados para Drunk driving


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The creation of three-dimensional (3D) drawings for proposed designs for construction, re-construction and rehabilitation activities are becoming increasingly common for highway designers, whether by department of transportation (DOT) employees or consulting engineers. However, technical challenges exist that prevent the use of these 3D drawings/models from being used as the basis of interactive simulation. Use of driving simulation to service the needs of the transportation industry in the US lags behind Europe due to several factors, including lack of technical infrastructure at DOTs, cost of maintaining and supporting simulation infrastructure—traditionally done by simulation domain experts—and cost and effort to translate DOT domain data into the simulation domain.

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The creation of three-dimensional (3D) drawings for proposed designs for construction, re-construction and rehabilitation activities are becoming increasingly common for highway designers, whether by department of transportation (DOT) employees or consulting engineers. However, technical challenges exist that prevent the use of these 3D drawings/models from being used as the basis of interactive simulation. Use of driving simulation to service the needs of the transportation industry in the US lags behind Europe due to several factors, including lack of technical infrastructure at DOTs, cost of maintaining and supporting simulation infrastructure—traditionally done by simulation domain experts—and cost and effort to translate DOT domain data into the simulation domain.

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The aim of this paper is to analyse how economic integration in Europe has affected industrial geographical concentration in Spain and explain what the driving forces behind industry location are. Firstly, we construct regional specialisation and geographical concentration indices for Spanish 50 provinces and 30 industrial sectors in 1979, 1986 and 1992. Secondly, we carry out an econometric analysis of the determinants of geographical concentration of industries. Our main conclusion is that there is no evidence of increasing specialisation in Spain between 1979 and 1992 and that the most important determinant of Spain¿s economic geography is scale economies. Furthermore, traditional trade theory has no effects in explaining the pattern of industrial concentration

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Except for the first 2 years since July 29, 1968, Arenal volcano has continuously erupted compositionally monotonous and phenocryst-rich (similar to35%) basaltic andesites composed of plagioclase (plag), orthopyroxene (opx), clinopyroxene (cpx), spinel olivine. Detailed textural and compositional analyses of phenocrysts, mineral inclusions, and microlites reveal comparable complexities in any given sample and identify mineral components that require a minimum of four crystallization environments. We suggest three distinct crystallization environments crystallized low Mg# (<78) silicate phases from andesitic magma but at different physical conditions, such as variable pressure of crystallization and water conditions. The dominant environment, i.e., the one which accounts for the majority of minerals and overprinted all other assemblages near rims of phenocrysts, cocrystallized clinopyroxene (Mg# similar to71-78), orthopyroxene (Mg# similar to71-78), titanomagnetite and plagioclase (An(60) to An(85)). The second environment cocrystallized clinopyroxene (Mg# 71-78), olivine (<Fo(78)), titanomagnetite, and very high An (similar to90) plagioclase, while the third cocrystallized clinopyroxene (Mg# 71-78) with high (>7) Al/Ti and high (>4 wt.%) Al2O3, titanomagnetite with considerable Al2O3 (10-18 wt.%) and possibly olivine but appears to lack plagioclase. A fourth crystallization environment is characterized by clinopyroxene (e.g., Mg#=similar to78-85; Cr2O3=0.15-0.7 wt.%), Al-, Cr-rich spinel olivine (similar toFo(80)), and in some circumstances high-An (>80) plagioclase. This assemblage seems to record mafic inputs into the Arenal system and crystallization at high to low pressures. Single crystals cannot be completely classified as xenocrysts, antecrysts (cognate crystals), or phenocrysts, because they often contain different parts each representing a different crystallization environment and thus belong to different categories. Bulk compositions are mostly too mafic to have crystallized the bulk of ferromagnesian minerals and thus likely do not represent liquid compositions. On the other hand, they are the cumulative products of multiple mixing events assembling melts and minerals from a variety of sources. The driving force for this multistage mixing evolution to generate erupting basaltic andesites is thought to be the ascent of mafic magma from lower crustal levels to subvolcanic depths which at the same time may also go through compositional modification by fractionation and assimilation of country rocks. Thus, mafic magmas become basaltic andesite through mixing, fractionation and assimilation by the time they arrive at subvolcanic depths. We infer new increments of basaltic andesite are supplied nearly continuously to the subvolcanic reservoir concurrently to the current eruption and that these new increments are blended into the residing, subvolcanic magma. Thus, the compositional monotony is mostly the product of repetitious production of very similar basaltic andesite. Furthermore, we propose that this quasi-constant supply of small increments of magma is the fundamental cause for small-scale, decade-long continuous volcanic activity; that is, the current eruption of Arenal is flux-controlled by inputs of mantle magmas. (C) 2004 Elsevier B.V. All rights reserved.

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A better integration of the information conveyed by traces within intelligence-led framework would allow forensic science to participate more intensively to security assessments through forensic intelligence (part I). In this view, the collection of data by examining crime scenes is an entire part of intelligence processes. This conception frames our proposal for a model that promotes to better use knowledge available in the organisation for driving and supporting crime scene examination. The suggested model also clarifies the uncomfortable situation of crime scene examiners who must simultaneously comply with justice needs and expectations, and serve organisations that are mostly driven by broader security objectives. It also opens new perspective for forensic science and crime scene investigation, by the proposal to follow other directions than the traditional path suggested by dominant movements in these fields.

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Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

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Cone photoreceptors mediate visual acuity under daylight conditions, so loss of cone-mediated central vision of course dramatically affects the quality of life of patients suffering from retinal degeneration. Therefore, promoting cone survival has become the goal of many ocular therapies and defining the stage of degeneration that still allows cell rescue is of prime importance. Using the Rpe65(R91W/R91W) mouse, which carries a mutation in the Rpe65 gene leading to progressive photoreceptor degeneration in both patients and mice, we defined stages of retinal degeneration that still allow cone rescue. We evaluated the therapeutic window within which cones can be rescued, using a subretinal injection of a lentiviral vector driving expression of RPE65 in the Rpe65(R91W/R91W) mice. Surprisingly, when applied to adult mice (1 month) this treatment not only stalls or slows cone degeneration but, actually, induces cone-specific protein expression that was previously absent. Before the intervention only part of the cones (40% of the number found in wild-type animals) in the Rpe65(R91W/R91W) mice expressed cone transducin (GNAT2); this fraction increased to 64% after treatment. Correct S-opsin localization is also recovered in the transduced region. In consequence these results represent an extended therapeutic window compared to the Rpe65(-/-) mice, implying that patients suffering from missense mutations might also benefit from a prolonged therapeutic window. Moreover, cones are not only rescued during the course of the degeneration, but can actually recover their initial status, meaning that a proportion of altered cones in chromophore deficiency-related disease can be rehabilitated even though they are severely affected.

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Excessive daytime sleepiness underpins a large number of the reported motor vehicle crashes. Fair and accurate field measures are needed to identify at-risk drivers who have been identified as potentially driving in a sleep deprived state on the basis of erratic driving behavior. The purpose of this research study was to evaluate a set of cognitive tests that can assist Motor Vehicle Enforcement Officers on duty in identifying drivers who may be engaged in sleep impaired driving. Currently no gold standard test exists to judge sleepiness in the field. Previous research has shown that Psychomotor Vigilance Task (PVT) is sensitive to sleep deprivation. The first goal of the current study was to evaluate whether computerized tests of attention and memory, more brief than PVT, would be as sensitive to sleepiness effects. The second goal of the study was to evaluate whether objective and subjective indices of acute and cumulative sleepiness predicted cognitive performance. Findings showed that sleepiness effects were detected in three out of six tasks. Furthermore, PVT was the only task that showed a consistent slowing of both ‘best’, i.e. minimum, and ‘typical’ responses, median RT due to sleepiness. However, PVT failed to show significant associations with objective measures of sleep deprivation (number of hours awake). The findings indicate that sleepiness tests in the field have significant limitations. The findings clearly show that it will not be possible to set absolute performance thresholds to identify sleep-impaired drivers based on cognitive performance on any test. Cooperation with industry to adjust work and rest cycles, and incentives to comply with those regulations will be critical components of a broad policy to prevent sleepy truck drivers from getting on the road.

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Despite a trend of decreasing teen fatalities due to motor vehicle crashes over the past decade, they remain the leading cause of adolescent fatalities in Iowa. The purpose of this study was to create detailed case studies of each fatal motor vehicle crash involving a driver under the age of 20 that occurred in Iowa in 2009, 2010, and 2011. Data for each crash were gathered from media sources, law enforcement agencies, and the Iowa Department of Transportation. The driving records of the teens, which included their licensure history, prior traffic citations, and prior crashes, were also acquired. In addition, data about the charges filed against a teen as a result of being involved in a fatal crash were obtained. A total of 126 crashes involving 131 teen drivers that resulted in 143 fatalities were analyzed. Many findings for fatal crashes involving teen drivers in Iowa are consistent with national trends, including the overrepresentation of male drivers, crash involvement that increases with age, crash involvement per vehicle miles traveled that decreases with age, and prevalence of single-vehicle road departure crashes. Relative to national statistics, teen fatalities from crashes in Iowa are more likely to occur from midnight to 6am and from 9am to noon. Crash type varied by driver age and county population level. Teen drivers contributed to the fatal crashes at a rate of 74%; contribution of the teen driver was unknown for 11% of crashes. Speed was a factor for about 25% of the crashes for which a teen driver was at fault. The same was also true of alcohol/drug impairment. Only 20% of the rear-seat occupants of the teen drivers’ vehicles wore seat belts compared to 60% use for the front-seat occupants. Analysis of the teens’ driving records prior to the fatal crash suggests at-fault crashes and speeding violations are associated with contributing to the fatal crash.

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The overarching goal of this project was to identify and evaluate cognitive and behavioral indices that are sensitive to sleep deprivation and may help identify commercial motor vehicle drivers (CMV) who are at-risk for driving in a sleep deprived state and may prove useful in field tests administered by officers. To that end, we evaluated indices of driver physiognomy (e.g., yawning, droopy eyelids, etc.) and driver behavioral/cognitive state (e.g. distracted driving) and the sensitivity of these indices to objective measures of sleep deprivation. The measures of sleep deprivation were sampled on repeated occasions over a period of 3.5-months in each of 44 drivers diagnosed with Obstructive Sleep Apnea (OSA) and 22 controls (matched for gender, age within 5 years, education within 2 years, and county of residence for rural vs. urban driving). Comprehensive analyses showed that specific dimensions of driver physiognomy associated with sleepiness in previous research and face-valid composite scores of sleepiness did not: 1) distinguish participants with OSA from matched controls; 2) distinguish participants before and after PAP treatment including those who were compliant with their treatment; 3) predict levels of sleep deprivation acquired objectively from actigraphy watches, not even among those chronically sleep deprived. Those findings are consistent with large individual differences in driver physiognomy. In other words, when individuals were sleep deprived as confirmed by actigraphy watch output they did not show consistently reliable behavioral markers of being sleep deprived. This finding held whether each driver was compared to him/herself with adequate and inadequate sleep, and even among chronically sleep deprived drivers. The scientific evidence from this research study does not support the use of driver physiognomy as a valid measure of sleep deprivation or as a basis to judge whether a CMV driver is too fatigued to drive, as on the current Fatigued Driving Evaluation Checklist.. Fair and accurate determinations of CMV driver sleepiness in the field will likely require further research on alternative strategies that make use of a combination of information sources besides driver physiognomy, including work logs, actigraphy, in vehicle data recordings, GPS data on vehicle use, and performance tests.

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Purpose: Current treatments for arthritis flares in gout (gouty arthritis) are not effective in all patients and may be contraindicated in many due to underlying comorbidities. Urate crystals activate the NALP 3 inflammasome which stimulate production of IL-1β, driving inflammatory processes. Targeted IL-1β blockade may be an alternative treatment for gouty arthritis. Canakinumab (ACZ885) is a fully human monoclonal anti- IL-1β antibody with a long half-life (28 days). Method: This was an 8-weeks, dose-ranging, multicenter, blinded, double-dummy, active-controlled trial of patients ≥18 to ≤80 y with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine. Patients were randomized to 1 subcutanous (sc) dose of canakinumab (10, 25, 50, 90, or 150 mg) or 1 intra muscular (im) dose of triamcinolone acetonide (TA) [40 mg]. The primary variable was assessed 72 h post-dose, measured on a 0-100 mm VAS pain scale. Secondary variables included pain intensity 24 and 48 h post dose, time to 50% reduction in pain intensity, and time to recurrence of gout flares up to 8 weeks post dose. Results: 200 patients were enrolled (canakinumab n=143, TA n=57) and 191 completed the study. A statistically significant dose response was observed at 72 h. The 150 mg dose reached superior pain relief compared to TA starting from 24h: estimated mean difference in pain intensity on 0-100 mm VAS was -11.5 at 24 h, -18.2 at 48 h, and -19.2 at 72 h (all p<0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg vs 2 days for the TA group (p=0.0006). The probability of recurrent gout flares was 3.7% with canakinumab 150 mg vs. 45.4% with TA 8 weeks post treatment, a relative risk reduction of 94% (p=0.006). Serious AEs occurred in 2 patients receiving canakinumab (appendicitis and carotid artery stenosis) and 1 receiving TA (cerebrovascular disorder). Investigator's reported these events as not study drug related. There were no discontinuations due to AEs. Conclusion: Canakinumab 150 mg provided faster onset and superior pain relief compared to TA for acute flares in gouty arthritis patients refractory to or contraindicated to standard treatments. The 150 mg dose of canakinumab prevented recurrence of gout flares with a relative risk reduction compared to TA of 94% at 8 weeks post-dose, and was well tolerated.

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This project examines the effects of age, experience, and video-based feedback on the rate and type of safety-relevant events captured on video event recorders in the vehicles of three groups of newly licensed young drivers: 1. 14.5- to 15.5-year-old drivers who hold a minor school license (see Appendix A for the provisions of the Iowa code governing minor school licenses); 2. 16-year-old drivers with an intermediate license who are driving unsupervised for the first time; 3. 16-year-old drivers with an intermediate license who previously drove unsupervised for at least four months with a school license. METHODS: The young drivers’ vehicles were equipped with an event-triggered video recording device for 24 weeks. Half of the participants received feedback regarding their driving, and the other half received no feedback at all and served as a control group. The number of safety-relevant events per 1,000 miles (i.e., “event rate”) was analyzed for 90 participants who completed the study. RESULTS: On average, the young drivers who received the video-based intervention had significantly lower event rates than those in the control group. This finding was true for all three groups. An effect of experience was seen for drivers in the control group; the 16-year-olds with driving experience had significantly lower event rates than the 16-year-olds without experience. When the intervention concluded, an increase in event rate was seen for the school license holders, but not for either group of 16-year-old drivers. There is strong evidence that giving young drivers video-based feedback, regardless of their age or level of driving experience, is effective in reducing the rate of safety-relevant events relative to a control group who do not receive feedback. Specific comparisons with regard to age and experience indicated that the age of the driver did not have an effect on the rate of safety-events, while experience did. Young drivers with six months or more of additional experience behind the wheel had nearly half as many safety-relevant events as those without that experience.

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Browse through this guide and you’ll find the distinct flavor of what is available along each byway. Discover recreational, historic, cultural and scenic attractions using the maps and lists provided in the guide. You’ll find numbered attractions for each byway in or near the town listed. For a comprehensive list of byway features, visit www.iowabyways.org. Friendly local contacts are provided to help you along the way. Iowa Transportation Maps clearly tracking all the Iowa byways with red dotted lines are available at Iowa’s official welcome centers. Traveling Iowa’s byways you will experience small town America, while enjoying diverse landscapes and unique landforms that have been shaped over thousands of years. Iowa’s cultural heritage also plays a major role across all 11 byways, boasting hundreds of historic sites, national landmarks and interpretive centers, each telling Iowa’s stories from the first Native Americans through European immigrants to modern times. Glaciers once covered much of Iowa, shaping the broad flat plains of the prairie. These massive sheets of ice missed the northeast corner of the state, leaving the land along the Driftless Area Byway rugged and hilly with rock outcroppings, springs and cold water trout streams. Rivers coursed their way through the land, carving deep furrows in some places and leaving gently rolling hills in others. In western Iowa, wind has shaped fine sand into the impressive Loess Hills, a rare land form found in only one other place on earth. Iowa’s two national scenic byways and nine state byways offer unique varieties of scenic features, and more for you to see and do. View three states from atop a Mississippi River bluff, stop at a modern art museum and then tour a working farm. Explore a historic mill, visit a national aquarium, take a boat ride in a cave, purchase locally crafted pottery and wares from local artisans or trace the footsteps of Lewis and Clark. Experience the actual wagon ruts of the Mormon Trail, ride your bike 13 stories high, canoe a water trail, star gaze under Iowa’s darkest sky, and marvel at mounds built by prehistoric cultures. Agriculture wraps Iowa’s byways with an abundance of farmland vistas and fills Iowa lands with ever-changing crops and activities for you to “harvest.” You’ll see croplands on the vast flat plains and farmsteads sprinkled across rolling hills reminiscent of a Grant Wood painting. Along the way, you might wander in a corn maze, rest at a bed and breakfast, study farming in museums, discover the Iowa barn quilt collection or visit a working Amish farm. When you are ready to step outside your vehicle, you’ll find much more to do and see. Prairie, forests, rivers and public lands are abundant along Iowa’s byways; providing opportunities for you to stop and play in the outdoors with hiking, biking, kayaking and trout fishing. Classic hometowns with pride for their unique lore and offerings are found all along the byways. They invite you to taste local food, enjoy their architecture, and immerse yourself in the rich history and culture that defines them. Why not plan your next journey off the beaten path? No matter how you choose to make the most of every moment, we know that time spent along Iowa’s byways is sure to grow your love for Iowa’s diverse, beautiful vistas and authentic communities. Happy driving!

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Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC) and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity and alveolar Na(+) absorption through a decrease of ENaC subunit expression at the apical membrane of alveolar epithelial cells (AECs). Here, we investigated the mechanism(s) involved in this process in vivo in the β-Liddle mouse strain mice carrying a truncation of β-ENaC C-terminus abolishing the interaction between β-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the channel for endocytosis and degradation and in vitro in rat AECs. Hypoxia (8% O2 for 24 h) reduced amiloride-sensitive alveolar fluid clearance by 69% in wild-type mice but had no effect in homozygous mutated β-Liddle littermates. In vitro, acute exposure of AECs to hypoxia (0.5-3% O2 for 1-6 h) rapidly decreased transepithelial Na(+) transport as assessed by equivalent short-circuit current Ieq and the amiloride-sensitive component of Na(+) current across the apical membrane, reflecting ENaC activity. Hypoxia induced a decrease of ENaC subunit expression in the apical membrane of AECs with no change in intracellular expression and induced a 2-fold increase in α-ENaC polyubiquitination. Hypoxic inhibition of amiloride-sensitive Ieq was fully prevented by preincubation with the proteasome inhibitors MG132 and lactacystin or with the antioxidant N-acetyl-cysteine. Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport.

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The crucial role of the proinflammatory cytokine interleukin 1β (IL-1β) in driving inflammatory disorders, such as Muckle-Wells syndrome and gout, has been extensively characterised. Owing to its high potency to induce inflammation the activation and secretion of IL-1β is tightly regulated. The sensing of various host 'dangers', including infections and metabolic deregulation, results in the formation of large protein complexes, termed inflammasomes. Formation of the inflammasomes leads to the cleavage and activation of caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1β. Biologically active IL-1β is subsequently secreted by the cell. In contrast to IL-1β, little is known about mechanisms underlying the activation and secretion of its close homologue IL-1α. Moreover, the physiological role of IL-1α is still not well defined. Several studies hypothesise that IL-1α serves as a danger signal, which is passively released from dying cells. However, recent studies suggest a more complex function of this cytokine. Indeed, NLRP3 inflammasome agonists such as uric acid crystal or nigericin induce IL-1α cleavage and secretion, leading to the cosecretion of both IL-1β and IL-1α. Depending on the type of NLRP3 agonist, release of IL-1α is NLRP3-inflammasome/caspase-1 dependent or independent, but in both cases IL-1α processing depends on calpain protease activity. Taken together, these results suggest that the promotion and progression of inflammatory diseases is not solely due to IL-1β but also to its close relative IL-1α. This should be considered when IL-1 blockade is applied as a therapeutic strategy for diseases such as cryopyrin-associated periodic syndromes or gout.