Publications by authors named "Jean-Louis Martin"

85 Publications

Estimated number of seriously injured road users admitted to hospital in France between 2010 and 2017, based on medico-administrative data.

BMC Public Health 2021 Mar 8;21(1):469. Epub 2021 Mar 8.

Univ Gustave Eiffel, Univ Lyon, Université Lyon 1, IFSTTAR, UMRESTTE UMR_T 9405, 25 avenue François Mitterrand, Bron, 69675, France.

Background: In France, like in most developed countries, the number of road accident fatalities is estimated from police data. These estimates are considered to be good-quality, unlike estimates of road injuries admitted to hospital, and especially serious injuries.

Methods: The present study aimed to supply such data from French hospital medical information data-bases (PMSI). In the PMSI data-bases, road accident victims are identified by external causes of morbidity and mortality, which should be systematically recorded in case of injury, but are often missing. We therefore modeled presence/absence of external cause from the relevant subset of the medicine-surgery-obstetrics PMSI data-base using a logistic regression, and then weighting the results by inverse estimated probability. As ICD-10 coding does not include injury severity, we used the AAAM10 conversion instrument developed by the American Association for Automotive Medicine, originators of the Abbreviated Injury Scale, so as to conform to the European Commission's definition of serious injury.

Results: The number of road-accident related hospital admissions is estimated to be about 100000 per year; serious injuries increased from about 18000 in 2010 to almost 20000 in 2017, with almost 17000 in 2012 and 2013, with a mean of one fatality per 5 serious injury admissions.

Conclusions: These serious injury estimates are close to those obtained by our team from other data and with a different estimation method. The present method has the advantage of using ICD codes for injured people admitted to hospital. This classification and data source (hospital discharge registry) are also used by most european countries reporting serious injury estimates to the Commission. It allows cost estimation of hospital care, and could be applied to other types of accidental injury.
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http://dx.doi.org/10.1186/s12889-021-10437-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938523PMC
March 2021

Deer slow down litter decomposition by reducing litter quality in a temperate forest.

Ecology 2021 Feb 30;102(2):e03235. Epub 2020 Nov 30.

Centre d'Écologie Fonctionnelle et Évolutive, UMR 5175, CNRS-Université de Montpellier-Université Paul Valéry-EPHE-IRD, 1919 route de Mende, F-34293, Montpellier, France.

Litter decomposition is a key process that allows the recycling of nutrients within ecosystems. In temperate forests, the role of large herbivores in litter decomposition remains a subject of debate. To address this question, we used two litterbag experiments in a quasiexperimental situation resulting from the introduction of Sitka black-tailed deer Odocoileus hemionus sitkensis on forested islands of Haida Gwaii (Canada). We investigated the two main pathways by which deer could modify litter decomposition: change in litter quality and modification of decomposer communities. We found that deer presence significantly reduced litter mass loss after 1 yr, mainly through a reduction in litter quality. This mass loss reflected a 30 and 28% lower loss of carbon (C) and nitrogen (N), respectively. The presence of deer also reduced the ability of decomposers to break down carbon, but not nitrogen. Indeed, litter placed on an island with deer lost 5% less carbon after 1 yr of decomposition than did litter decomposing on an island without deer. This loss in ability to decompose litter in the presence of deer was outweighed by the differences in mass loss associated with the effect of deer on litter quality. Additional effects of feces deposition by deer on the decomposition process were also significant but minor. These results suggest that the effects dramatic continental-scale increases in deer populations may have on broad-scale patterns of C and N cycling deserve closer attention.
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http://dx.doi.org/10.1002/ecy.3235DOI Listing
February 2021

Biodiversity policy beyond economic growth.

Conserv Lett 2020 Jul-Aug;13(4):e12713. Epub 2020 Apr 13.

German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig Leipzig Germany.

Increasing evidence-synthesized in this paper-shows that economic growth contributes to biodiversity loss via greater resource consumption and higher emissions. Nonetheless, a review of international biodiversity and sustainability policies shows that the majority advocate economic growth. Since improvements in resource use efficiency have so far not allowed for absolute global reductions in resource use and pollution, we question the support for economic growth in these policies, where inadequate attention is paid to the question of how growth can be decoupled from biodiversity loss. Drawing on the literature about alternatives to economic growth, we explore this contradiction and suggest ways forward to halt global biodiversity decline. These include policy proposals to move beyond the growth paradigm while enhancing overall prosperity, which can be implemented by combining top-down and bottom-up governance across scales. Finally, we call the attention of researchers and policy makers to two immediate steps: acknowledge the conflict between economic growth and biodiversity conservation in future policies; and explore socioeconomic trajectories beyond economic growth in the next generation of biodiversity scenarios.
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http://dx.doi.org/10.1111/conl.12713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507775PMC
April 2020

Deer, wolves, and people: costs, benefits and challenges of living together.

Biol Rev Camb Philos Soc 2020 06 11;95(3):782-801. Epub 2020 Feb 11.

Department of Botany, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Human-driven species annihilations loom as a major crisis. However the recovery of deer and wolf populations in many parts of the northern hemisphere has resulted in conflicts and controversies rather than in relief. Both species interact in complex ways with their environment, each other, and humans. We review these interactions in the context of the ecological and human costs and benefits associated with these species. We integrate scattered information to widen our perspective on the nature and perception of these costs and benefits and how they link to each other and ongoing controversies regarding how we manage deer and wolf populations. After revisiting the ecological roles deer and wolves play in contemporary ecosystems, we explore how they interact, directly and indirectly, with human groups including farmers, foresters, shepherds, and hunters. Interactions with deer and wolves generate various axes of tension, posing both ecological and sociological challenges. Resolving these tensions and conflicts requires that we address key questions using integrative approaches: what are the ecological consequences of deer and wolf recovery? How do they influence each other? What are the social and socio-ecological consequences of large deer populations and wolf presence? Finally, what key obstacles must be overcome to allow deer, wolves and people to coexist? Reviewing contemporary ecological and sociological results suggests insights and ways to improve our understanding and resolve long-standing challenges to coexistence. We should begin by agreeing to enhance aggregate benefits while minimizing the collective costs we incur by interacting with deer and wolves. We should also view these species, and ourselves, as parts of integrated ecosystems subject to long-term dynamics. If co-existence is our goal, we need deer and wolves to persevere in ways that are compatible with human interests. Our human interests, however, should be inclusive and fairly value all the costs and benefits deer and wolves entail including their intrinsic value. Shifts in human attitudes and cultural learning that are already occurring will reshape our ecological interactions with deer and wolves.
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http://dx.doi.org/10.1111/brv.12587DOI Listing
June 2020

Prediction of responsibility for drivers and riders involved in injury road crashes.

J Safety Res 2019 09 9;70:159-167. Epub 2019 Jul 9.

Univ Lyon, Université Lyon 1, IFSTTAR, UMRESTTE UMR_T 9405, F-69675 Lyon, France. Electronic address:

Introduction: Responsibility analysis allows the evaluation of crash risk factors from crash data only, but requires a reliable responsibility assessment. The aim of the present study is to predict expert responsibility attribution (considered as a gold-standard) from explanatory variables available in crash data routinely recorded by the police, according to a data-driven process with explicit rules.

Method: Driver responsibility was assessed by experts using all information contained in police reports for a sample of about 5000 injury crashes that occurred in France in 2011. Three statistical methods were used to predict expert responsibility attribution: logistic regression with L1 penalty, random forests, and boosting. Potential predictors of expert attribution referred to inappropriate driver actions and to external conditions at the time of the crash. Logistic regression was chosen to construct a score to assess responsibility for drivers and riders in crashes involving one or more motor vehicles, or involving a cyclist or pedestrian.

Results: Cross-validation showed that our tool can predict expert responsibility assessments on new data sets. In addition, responsibility analyses performed using either the expert responsibility or our predicted responsibility return similar odds ratios. Our scoring process can then be used to reliably assess responsibility based on national police report databases, provided that they include the information needed to construct the score.
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http://dx.doi.org/10.1016/j.jsr.2019.07.001DOI Listing
September 2019

Descriptive analysis of the effect of back protector on the prevention of vertebral and thoracolumbar injuries in serious motorcycle accident.

Accid Anal Prev 2020 Feb 18;135:105331. Epub 2019 Nov 18.

iLab-Spine - Laboratoire international en imagerie et biomécanique du Rachis, Marseille, France; Department of Neurosurgery, Trauma centre, Hôpital Nord, Marseille, France.

Context And Objective: Among the different products and protective gear used by riders of two-wheeled motorized vehicles, back protectors that are designed to prevent damage to the spinal column are widely used today compared other protections. However, few studies measure their effectiveness. Can their effectiveness be measured? How do they help decrease or change the nature of thoracolumbar traumas that occur? To address these questions and remedy the lack of objective data regarding these products, an epidemiological, clinical, and biomechanical analysis of motorcycle riders who were admitted to a French trauma center after an accident was performed. So, this study investigates the effectiveness of back protectors, including their ability to prevent specific mechanisms of thoracic and lumbar spinal injuries related to TWMV accidents.

Method: A questionnaire was administered to victims of accidents involving two-wheeled motorized vehicles who were admitted to the trauma room at the Marseille trauma center over the course of 2016. Collect data are related to the victim, the accident scenario, and a detailed description of the observed injuries using AIS (Abbreviated Injury Scale) coding and Magerl classification. Univariate analyses and Fisher tests were performed for victims who were or were not wearing back protectors.

Results: This study collected data from 124 victims. Almost half of the victims were wearing a back protector at the time of the accident (53 victims, thus 43% of riders). Collectively, twenty-nine victims who were wearing back protectors had 57 thoracolumbar injuries, and twenty eight victims who were not wearing back protectors had 75 thoracolumbar lesions. The results from this study show that there is no significant difference in the nature and mechanism of thoracolumbar injuries as a function of back protection. The majority of the thoracolumbar injuries were not severe. They were primarily bone injuries, essentially compression fractures, regardless of whether a back protector was worn.

Conclusion: This study shows that the use of back protection does not decrease the number, type, or mechanism of thoracolumbar injuries associated with accidents involving two-wheeled motorized vehicles. However, it suggests that lumbar vertebral injuries are deflected towards the thoracic vertebrae when back protectors are worn. Finally, it suggests that the design of back protectors should be reconsidered to better protect riders from what are referred to as compression fractures (craniocaudal force), which remain the primary form of fracture regardless of the rider's characteristics, based on the data analyzed.
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http://dx.doi.org/10.1016/j.aap.2019.105331DOI Listing
February 2020

Increasing crop heterogeneity enhances multitrophic diversity across agricultural regions.

Proc Natl Acad Sci U S A 2019 08 29;116(33):16442-16447. Epub 2019 Jul 29.

Geomatics and Landscape Ecology Laboratory, Carleton University, Ottawa, ON K1S 5B6, Canada.

Agricultural landscape homogenization has detrimental effects on biodiversity and key ecosystem services. Increasing agricultural landscape heterogeneity by increasing seminatural cover can help to mitigate biodiversity loss. However, the amount of seminatural cover is generally low and difficult to increase in many intensively managed agricultural landscapes. We hypothesized that increasing the heterogeneity of the crop mosaic itself (hereafter "crop heterogeneity") can also have positive effects on biodiversity. In 8 contrasting regions of Europe and North America, we selected 435 landscapes along independent gradients of crop diversity and mean field size. Within each landscape, we selected 3 sampling sites in 1, 2, or 3 crop types. We sampled 7 taxa (plants, bees, butterflies, hoverflies, carabids, spiders, and birds) and calculated a synthetic index of multitrophic diversity at the landscape level. Increasing crop heterogeneity was more beneficial for multitrophic diversity than increasing seminatural cover. For instance, the effect of decreasing mean field size from 5 to 2.8 ha was as strong as the effect of increasing seminatural cover from 0.5 to 11%. Decreasing mean field size benefited multitrophic diversity even in the absence of seminatural vegetation between fields. Increasing the number of crop types sampled had a positive effect on landscape-level multitrophic diversity. However, the effect of increasing crop diversity in the landscape surrounding fields sampled depended on the amount of seminatural cover. Our study provides large-scale, multitrophic, cross-regional evidence that increasing crop heterogeneity can be an effective way to increase biodiversity in agricultural landscapes without taking land out of agricultural production.
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http://dx.doi.org/10.1073/pnas.1906419116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697893PMC
August 2019

Does a full-face helmet effectively protect against facial injuries?

Inj Epidemiol 2019 1;6:19. Epub 2019 Jun 1.

Univ Lyon, Université Lyon 1, IFSTTAR, UMRESTTE UMR_T 9405, 25 Avenue François Mitterrand, 69675 Bron Cedex, France.

Background: The effectiveness of helmet use in preventing or reducing the severity of head injuries has been largely demonstrated. However, the effectiveness of different types of helmets in reducing facial or non-facial head injuries has received much less attention.

Methods: A postal survey on motorized two-wheeler crashes was conducted in 2016. 7148 riders of motorized two-wheelers (MTW) injured in a crash between 2010 and 2014 and identified in the Rhône Trauma Registry were invited to complete a questionnaire in order to collect detailed information about their accidents. The analysis was based on a population of 405 helmeted riders who declared having received an impact on the head. Facial and non-facial head injury risks were estimated according to helmet type (full face or other) by logistic regression, controlled for type of object hit by the head (and gender for risk of non-facial head injury), and weighted to take nonresponse into account.

Results: Three-quarter of helmeted MTW drivers were wearing a full-face helmet at the time of the accident. Victims wearing a full-face helmet were about three times less likely to have sustained injury to the face, compared to victims wearing another type of helmet (adjusted OR = 0.31; 95% CI: 0.11-0.83). On the other hand, the presence of non-facial head injury did not vary significantly according to whether a full-face or other helmet was worn (adjusted OR = 0.84; 95% CI: 0.33-2.13).

Conclusions: Our study suggests that full-face helmets provide better facial protection for MTW users compared to other types of helmets, whereas there is no evidence of any difference in protection afforded the skull or the brain.
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http://dx.doi.org/10.1186/s40621-019-0197-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544930PMC
June 2019

Analysis of trunk impact conditions in motorcycle road accidents based on epidemiological, accidentological data and multibody simulations.

Accid Anal Prev 2019 Jun 25;127:223-230. Epub 2019 Mar 25.

Aix-Marseille Univ, IFSTTAR, LBA UMR_T24, F-13016, Marseille, France. Electronic address:

Motorcycle accidents lead to a high rate of traffic mortality and morbidity. While helmet development and mandatory wearing have reduced head injuries, little progress has been made regarding trunk protection. Wearable airbag devices represent a promising solution to prevent trunk injuries. Nevertheless, research investigations need to be performed to assess and optimise the efficiency of such devices. This work consisted in the analysis of motorcyclist trunk impact conditions involved in various crash configurations to provide critical information in order to evaluate and improve the performances of airbag devices. First, an epidemiological and an accidentological analysis of data collection related to 252 real accidents, focusing on victims admitted into the shock rooms of two French trauma centres were performed. The data obtained was combined with numerical multibody parametric investigations, allowing the reproduction of 240 accident situations. An original and representative analysis of motorcyclists' impact conditions was provided, weighting the numerical study output data according to the real accident database. The impacted regions of the human body, the impact velocity and the accident chronology obtained in this work made it possible to define critical information for airbag efficiency assessment: the zones and levels of protection, the impacted surfaces as well as the airbag intervention time and the duration of maintained inflation of the airbag.
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http://dx.doi.org/10.1016/j.aap.2019.03.006DOI Listing
June 2019

Effectiveness of protective clothing for motorized 2-wheeler riders.

Traffic Inj Prev 2019 22;20(2):196-203. Epub 2019 Mar 22.

a Univ Lyon, Université Lyon 1, IFSTTAR, UMRESTTE UMR_T 9405 , Lyon , France.

Objective: This study assesses the effectiveness of protective clothing (motorcycle jacket, trousers, gloves, knee-high or ankle boots, back protection) for motorized 2-wheeler (MTW) riders.

Methods: This retrospective observational study used injury data from the Rhône Registry of Road Accident Victims, plus a postal survey conducted in 2016. Seven thousand one hundred forty-eight MTW riders involved in accidents between 2010 and 2014 were identified from the Registry and were invited to complete a questionnaire. Nine hundred seventy-nine individuals returned the questionnaire with relevant information; 951 with complete injury descriptions and clothing information were included in the study. The impact of protective clothing on injury risk was estimated using Poisson regression, with weighting for nonrespondents.

Results: Sixty-seven percent of MTW riders sustained upper limb injuries and 47% sustained lower limb injuries. Gloves were the most frequent gear worn (76%), followed by jackets (59%) and knee-high or ankle boots (37%). Only 23% had back protection and 0.3% had an airbag. Wearing protective clothing was associated with a lower risk of soft tissue injury to upper and lower limbs: For upper limbs, the risk was lower when one of 2 items (a motorcycle jacket or gloves) was worn (relative risk [RR] = 0.36; 95% confidence interval [CI], 0.18-0.75) and was lowest when both were worn (RR = 0.28; 95% CI, 0.12-0.69); for lower limbs, risk was reduced by wearing both motorcycle trousers and boots (RR = 0.60; 95% CI, 0.40-0.91) but was not significantly reduced when only one of these items was worn (RR = 0.90; 95% CI, 0.67-1.21). This protective effect was mainly due to a reduction in abrasions/lacerations rather than contusions. However, protective clothing did not reduce the risk of fracture, dislocation, or sprain, except for knee-high or ankle boots, which were associated with lower risk of ankle or foot fracture (RR = 0.43; 95% CI, 0.24-0.75). No effect of back protectors was shown.

Conclusions: This study confirms the potential for motorcycle clothing to protect users from injury, in particular abrasions and lacerations. However, it did not show any significant protective effect against more serious injuries, such as fracture, dislocation, or sprain, except for knee-high or ankle boots, which reduced foot and ankle fracture risk. Our results argue for more widespread use of protective clothing by MTW users.
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http://dx.doi.org/10.1080/15389588.2018.1545090DOI Listing
June 2019

Landscape configurational heterogeneity by small-scale agriculture, not crop diversity, maintains pollinators and plant reproduction in western Europe.

Proc Biol Sci 2018 02;285(1872)

Agroecology, Department of Crop Science, University of Goettingen, Goettingen, Germany.

Agricultural intensification is one of the main causes for the current biodiversity crisis. While reversing habitat loss on agricultural land is challenging, increasing the farmland configurational heterogeneity (higher field border density) and farmland compositional heterogeneity (higher crop diversity) has been proposed to counteract some habitat loss. Here, we tested whether increased farmland configurational and compositional heterogeneity promote wild pollinators and plant reproduction in 229 landscapes located in four major western European agricultural regions. High-field border density consistently increased wild bee abundance and seed set of radish (), probably through enhanced connectivity. In particular, we demonstrate the importance of crop-crop borders for pollinator movement as an additional experiment showed higher transfer of a pollen analogue along crop-crop borders than across fields or along semi-natural crop borders. By contrast, high crop diversity reduced bee abundance, probably due to an increase of crop types with particularly intensive management. This highlights the importance of crop identity when higher crop diversity is promoted. Our results show that small-scale agricultural systems can boost pollinators and plant reproduction. Agri-environmental policies should therefore aim to halt and reverse the current trend of increasing field sizes and to reduce the amount of crop types with particularly intensive management.
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http://dx.doi.org/10.1098/rspb.2017.2242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829195PMC
February 2018

Burden of injury of serious road injuries in six EU countries.

Accid Anal Prev 2018 Feb 7;111:184-192. Epub 2017 Dec 7.

Loughborough Design School, Loughborough University, LE11 3TU, UK.

Background: Information about the burden of (non-fatal) road traffic injury is very useful to further improve road safety policy. Previous studies calculated the burden of injury in individual countries. This paper estimates and compares the burden of non-fatal serious road traffic injuries in six EU countries/regions: Austria, Belgium, England, The Netherlands, the Rhône region in France and Spain.

Methods: It is a cross-sectional study based on hospital discharge databases.

Population: of study are patients hospitalized with MAIS3+ due to road traffic injuries. The burden of injury (expressed in years lived with disability (YLD)) is calculated applying a method that is developed within the INTEGRIS study. The method assigns estimated disability information to the casualties using the EUROCOST injury classification.

Results: The average burden per MAIS3+ casualty varies between 2.4 YLD and 3.2 YLD per casualty. About 90% of the total burden of injury of MAIS3+ casualties is due to lifelong consequences that are experienced by 19% to 33% of the MAIS3+ casualties. Head injuries, spinal cord injuries and injuries to the lower extremities are responsible for more than 90% of the total burden of MAIS3+ road traffic injuries. Results per transport mode differ between the countries. Differences between countries are mainly due to differences in age distribution and in the distribution over EUROCOST injury groups of the casualties.

Conclusion: The analyses presented in this paper can support further improvement of road safety policy. Countermeasures could for example be focused at reducing skull and brain injuries, spinal cord injuries and injuries to the lower extremities, as these injuries are responsible for more than 90% of the total burden of injury of MAIS3+ casualties.
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http://dx.doi.org/10.1016/j.aap.2017.11.040DOI Listing
February 2018

Risk factors for motorcycle loss-of-control crashes.

Traffic Inj Prev 2018 05 23;19(4):433-439. Epub 2018 Feb 23.

a Univ Lyon , Université Lyon 1 , IFSTTAR, UMRESTTE UMR_T 9405, Lyon , France.

Objective: The present article identifies and assesses the effect of critical factors on the risk of motorcycle loss-of-control (LOC) crashes.

Method: Data come from a French project on road crashes, which include all fatal road crashes and a random sample of 1/20th of nonfatal crashes in France in 2011, based on police reports. A case-control study was carried out on a sample of 903 crashes for 444 LOC motorcycle riders (case) and 470 non-LOC and nonresponsible motorcycle riders (control). The sample was weighted due to the randomization of nonfatal crashes. Missing values were imputed using multiple imputation.

Results: Road alignment and surface conditions, human factors, and motorcycle type played important roles in motorcycle LOC crashes. Riding in a curve was associated with a 3-fold greater risk of losing control of motorcycle than riding in a straight line. Poor road adhesion significantly increased the risk of losing control; the risk increased more than 20-fold when deteriorated road adhesion was encountered unexpectedly, due to loose gravel, ice, oil, bumps, road marking, metal plates, etc. For motorcyclists, riding with a positive blood alcohol concentration (over or equal to the legal limit of 0.5 g/L) was very dangerous, often resulting in losing control. The risk of LOC crash varied for different types of motorcycle: Riders of roadsters and sports bikes were more likely to have an LOC crash greater than that of riders of basic or touring motorcycles. In addition, LOC risk increased with speed; a model using the square of the traveling speed showed better fit than one using speed itself.

Conclusion: The LOC crash factors related to riders, vehicles, and road infrastructure identified here were expected but were rarely identified and taken simultaneously into account in previous studies. They could be targeted by countermeasures to improve motorcyclist safety.
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http://dx.doi.org/10.1080/15389588.2017.1410145DOI Listing
May 2018

Cannabis, alcohol and fatal road accidents.

PLoS One 2017 8;12(11):e0187320. Epub 2017 Nov 8.

Univ Lyon, Université Claude Bernard Lyon 1, Ifsttar, UMRESTTE, UMR_T 9405, Bron, France.

Introduction: This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003.

Methodology: Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general.

Results: The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1-26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed.

Conclusion: Almost a decade separates the present study from a similar one previously conducted in France, and there have been numerous developments in the intervening years. Even so, the prevalence of drivers responsible for causing fatal accidents under the influence of alcohol or narcotics has stayed remarkably stable, as have the proportion of fatal accidents which could in theory be prevented if no drivers ever exceeded the legal limits. The overall number of deaths from traffic accidents has dropped sharply during this period, and the number of victims attributable to alcohol and/or cannabis declined proportionally. Alcohol remains the main problem in France. It is just as important to note that one in two drivers considered to be under the influence of cannabis was also under the influence of alcohol. With risks cumulating between the two, it is particularly important to point out the danger of consuming them together.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187320PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678710PMC
November 2017

Structural changes and picosecond to second dynamics of cytochrome c in interaction with nitric oxide in ferrous and ferric redox states.

Phys Chem Chem Phys 2017 Aug;19(32):21317-21334

Laboratoire Jean Perrin, Sorbonne Universités, UPMC Univ. Paris 06, CNRS, 75005 Paris, France.

Apart from its role in electron transfer, mitochondrial cytochrome c also plays a role in apoptosis and is subject to nitrosylation. The cleavage of the Fe-Met80 bond plays a role in several processes including the release of Cyt c from mitochondria or increase of its peroxidase activity. Nitrosylation of Cyt c precludes the reformation of the disrupted Fe-Met80 bond and was shown to occur during apoptosis. These physiological properties are associated with a conformational change of the heme center of Cyt c. Here, we demonstrate that NO binding induces pronounced heme conformational changes in the six-coordinate Cyt c-NO complex. Equilibrium and time-resolved Raman data reveal that the heme structural conformation depends both on the nature of the distal iron ligand (NO or Met80) and on the Fe or Fe heme redox state. Upon nitrosylation, the heme ruffling distortion is greatly enhanced for ferrous Cyt c. Contrastingly, the initial strong heme distortion in native ferric Cyt c almost disappears after NO binding. We measured the heme coordination dynamics in the picosecond to second time range and identified Met80 and NO rebinding phases using time-resolved Raman and absorption spectroscopies. Dissociation of NO instantly produces 5-coordinate heme with a domed structure which continues to rearrange within 15 ps, while the initial ruffling distortion disappears. The rates of Cyt c-NO complex formation measured by transient absorption are k = 1.81 × 10 M s for ferric Cyt c and 83 M s for ferrous Cyt c. After NO dissociation and exit from the heme pocket, the rebinding of Met80 to the heme iron takes place 6 orders of magnitude more slowly (3-5 μs) than Met80 rebinding in the absence of NO (5 ps). Altogether, these data reveal the structural and dynamic properties of Cyt c in interaction with nitric oxide relevant for the molecular mechanism of apoptosis.
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http://dx.doi.org/10.1039/c7cp02634jDOI Listing
August 2017

Pedestrian fatality and impact speed squared: Cloglog modeling from French national data.

Traffic Inj Prev 2018 01 30;19(1):94-101. Epub 2017 May 30.

a Univ Lyon, Université Lyon 1, IFSTTAR, UMRESTTE UMR_T 9405 , Lyon , France.

Objective: The present study estimates pedestrians' risk of death according to impact speed when hit by a passenger car in a frontal collision.

Methods: Data were coded for all fatal crashes in France in 2011 and for a random sample of 1/20th of all road injuries for the same year and weighted to take into account police underreporting of mild injury. A cloglog model was used to optimize risk adjustment for high collision speeds. The fit of the model on the data was also improved by using the square of the impact speed, which best matches the energy dissipated in the collision.

Results: Modeling clearly demonstrated that the risk of death was very close to 1 when impact speeds exceeded 80 km/h. For speeds less than 40 km/h, because data representative of all crashes resulting in injury were used, the estimated risk of death was fairly low. However, although the curve seemed deceptively flat below 50 km/h, the risk of death in fact rose 2-fold between 30 and 40 km/h and 6-fold between 30 and 50 km/h. For any given speed, the risk of death was much higher for more elderly subjects, especially those over 75 years of age. These results concern frontal crashes involving a passenger car. Collisions involving trucks are far less frequent, but half result in the pedestrian being run over, incurring greater mortality.

Conclusions: For impact speeds below 60 km/h, the shape of the curve relating probability of death to impact speed was very similar to those reported in recent rigorous studies. For higher impact speeds, the present model allows the curve to rise ever more steeply, giving a much better fit to observed data. The present results confirm that, when a pedestrian is struck by a car, impact speed is a major risk factor, thus providing a supplementary argument for strict speed limits in areas where pedestrians are highly exposed.
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http://dx.doi.org/10.1080/15389588.2017.1332408DOI Listing
January 2018

The need to respect nature and its limits challenges society and conservation science.

Proc Natl Acad Sci U S A 2016 May 16;113(22):6105-12. Epub 2016 May 16.

Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN 37996

Increasing human population interacts with local and global environments to deplete biodiversity and resources humans depend on, thus challenging societal values centered on growth and relying on technology to mitigate environmental stress. Although the need to address the environmental crisis, central to conservation science, generated greener versions of the growth paradigm, we need fundamental shifts in values that ensure transition from a growth-centered society to one acknowledging biophysical limits and centered on human well-being and biodiversity conservation. We discuss the role conservation science can play in this transformation, which poses ethical challenges and obstacles. We analyze how conservation and economics can achieve better consonance, the extent to which technology should be part of the solution, and difficulties the "new conservation science" has generated. An expanded ambition for conservation science should reconcile day-to-day action within the current context with uncompromising, explicit advocacy for radical transitions in core attitudes and processes that govern our interactions with the biosphere. A widening of its focus to understand better the interconnectedness between human well-being and acknowledgment of the limits of an ecologically functional and diverse planet will need to integrate ecological and social sciences better. Although ecology can highlight limits to growth and consequences of ignoring them, social sciences are necessary to diagnose societal mechanisms at work, how to correct them, and potential drivers of social change.
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http://dx.doi.org/10.1073/pnas.1525003113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896672PMC
May 2016

Motion of proximal histidine and structural allosteric transition in soluble guanylate cyclase.

Proc Natl Acad Sci U S A 2015 Apr 23;112(14):E1697-704. Epub 2015 Mar 23.

Laboratoire d'Optique et Biosciences, INSERM U1182, Ecole Polytechnique, 91128 Palaiseau Cedex, France; and

We investigated the changes of heme coordination in purified soluble guanylate cyclase (sGC) by time-resolved spectroscopy in a time range encompassing 11 orders of magnitude (from 1 ps to 0.2 s). After dissociation, NO either recombines geminately to the 4-coordinate (4c) heme (τG1 = 7.5 ps; 97 ± 1% of the population) or exits the heme pocket (3 ± 1%). The proximal His rebinds to the 4c heme with a 70-ps time constant. Then, NO is distributed in two approximately equal populations (1.5%). One geminately rebinds to the 5c heme (τG2 = 6.5 ns), whereas the other diffuses out to the solution, from where it rebinds bimolecularly (τ = 50 μs with [NO] = 200 μM) forming a 6c heme with a diffusion-limited rate constant of 2 × 10(8) M(-1)⋅s(-1). In both cases, the rebinding of NO induces the cleavage of the Fe-His bond that can be observed as an individual reaction step. Saliently, the time constant of bond cleavage differs depending on whether NO binds geminately or from solution (τ5C1 = 0.66 μs and τ5C2 = 10 ms, respectively). Because the same event occurs with rates separated by four orders of magnitude, this measurement implies that sGC is in different structural states in both cases, having different strain exerted on the Fe-His bond. We show here that this structural allosteric transition takes place in the range 1-50 μs. In this context, the detection of NO binding to the proximal side of sGC heme is discussed.
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http://dx.doi.org/10.1073/pnas.1423098112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394285PMC
April 2015

Prognosis of outcome in adult survivors of road accidents in France: one-year follow-Up in the ESPARR cohort.

Traffic Inj Prev 2014 ;15(2):138-47

a IFSTTAR, UMRESTTE, Université de Lyon , Lyon , France.

Objective: The consequences of road crashes are various, and few studies have dealt with the multidimensionality of outcomes. The aim of the present study was to assess the multidimensional nature of outcomes one year after a crash and to determine predictive factors that could help in adapting medical and social care to prevent such consequences to improve road crash victims' prognosis.

Methods: The study population was the 886 respondents to the one-year follow-up from the ESPARR (Etude et Suivi d'une Population d'Accidentés de la Route du Rhône) cohort, aged ≥ 16 years; the analysis was carried out only on the 616 subjects who fully completed a self-report questionnaire on health, social, emotional, and financial status one year after a crash. Multiple correspondence analysis and hierarchical clustering was implemented to produce homogeneous groups according to differences in outcome. Groups were compared using the World Health Organization Quality of Life Assessment (WHOQOL-BREF, a standard instrument of quality of life, assessing physical health, psychological health, social relationships, and environment) and the Injury Impairment Scale (IIS), a tool to predict road crash sequelae. Baseline predictive factors for group attribution were analyzed by weighted multinomial logistic regression models.

Results: Three hundred seventeen of the 616 subjects (60.1%) were men. Mean age was 36.9 years (SD = 16.5). Five victim groups were identified in terms of consequences at one year: one group (206 subjects, 33.4%) with few problems, one with essentially physical sequelae, one with problems that were essentially both physical and social, and 2 groups with a wider range of problems (one including psychological problems but fewer environmental problems; the last one reported negative physical, psychological, social, and environmental impact; notably, all had post-concussion syndrome [PCS]). There were significant differences between groups in terms of family status, injury severity, and certain types of injury (thorax, spine, lower limbs). Comparison on the WHOQOL-BREF confirmed that groups reporting more adverse outcomes had a lower quality of life. Description of the 5 groups by IIS indicators showed that IIS underestimated physical consequences one year after the crash. In addition to the known prognostic factors such as age, initial injury severity, and injury type, socioeconomic fragility and having a relative involved in the accident emerged as predictive of poor outcome at one year.

Conclusions: One year after the crash, victims may still be experiencing multiple problems in terms of not only physical health but also of mental health, social life, and environment. Poor outcome may be predicted from both accident-related factors and socioeconomic fragility. Our results are useful in catching the attention of both clinicians and the public administration regarding victims at risk of suffering from important consequences after an accident. If those suffering head injuries are recognized, it would be very important to better consider and treat posttraumatic stress disorder (PTSD) or PCS. Furthermore, subjects from lower socioeconomic backgrounds, with or without lower limb injuries, have numerous difficulties after an accident, notably for returning to work. An objective would be to provide them with more specific support. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.
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http://dx.doi.org/10.1080/15389588.2013.804180DOI Listing
February 2014

Innate threat-sensitive foraging: black-tailed deer remain more fearful of wolf than of the less dangerous black bear even after 100 years of wolf absence.

Oecologia 2014 Apr 28;174(4):1151-8. Epub 2013 Nov 28.

Centre d'Ecologie Fonctionnelle et Evolutive, CNRS, UMR 5175, 1919 Route de Mende, 34293, Montpellier Cedex 5, France,

Anti-predator behaviors often entail foraging costs, and thus prey response to predator cues should be adjusted to the level of risk (threat-sensitive foraging). Simultaneously dangerous predators (with high hunting success) should engender the evolution of innate predator recognition and appropriate anti-predator behaviors that are effective even upon the first encounter with the predator. The above leads to the prediction that prey might respond more strongly to cues of dangerous predators that are absent, than to cues of less dangerous predators that are actually present. In an applied context this would predict an immediate and stronger response of ungulates to the return of top predators such as wolves (Canis lupus) in many parts of Europe and North America than to current, less threatening, mesopredators. We investigated the existence of innate threat-sensitive foraging in black-tailed deer. We took advantage of a quasi-experimental situation where deer had not experienced wolf predation for ca. 100 years, and were only potentially exposed to black bears (Ursus americanus). We tested the response of deer to the urine of wolf (dangerous) and black bear (less dangerous). Our results support the hypothesis of innate threat-sensitive foraging with clear increased passive avoidance and olfactory investigation of cues from wolf, and surprisingly none to black bear. Prey which have previously evolved under high risk of predation by wolves may react strongly to the return of wolf cues in their environments thanks to innate responses retained during the period of predator absence, and this could be the source of far stronger non-consumptive effects of the predator guild than currently observed.
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http://dx.doi.org/10.1007/s00442-013-2843-0DOI Listing
April 2014

Reactivity and dynamics of H2S, NO, and O2 interacting with hemoglobins from Lucina pectinata.

Biochemistry 2013 Oct 27;52(40):7007-21. Epub 2013 Sep 27.

Department of Chemistry, University of Puerto Rico , Mayagüez Campus, Mayagüez 00680, Puerto Rico.

Hemoglobin HbI from the clam Lucina pectinata is involved in H2S transport, whereas homologous heme protein HbII/III is involved in O2 metabolism. Despite similar tertiary structures, HbI and HbII/III exhibit very different reactivity toward heme ligands H2S, O2, and NO. To investigate this reactivity at the heme level, we measured the dynamics of ligand interaction by time-resolved absorption spectroscopy in the picosecond to nanosecond time range. We demonstrated that H2S can be photodissociated from both ferric and ferrous HbI. H2S geminately rebinds to ferric and ferrous out-of-plane iron with time constants (τgem) of 12 and 165 ps, respectively, with very different proportions of photodissociated H2S exiting the protein (24% in ferric and 80% in ferrous HbI). The Gln(E7)His mutation considerably changes H2S dynamics in ferric HbI, indicating the role of Gln(E7) in controling H2S reactivity. In ferric HbI, the rate of diffusion of H2S from the solvent into the heme pocket (kentry) is 0.30 μM(-1) s(-1). For the HbII/III-O2 complex, we observed mainly a six-coordinate vibrationally excited heme-O2 complex with O2 still bound to the iron. This explains the low yield of O2 photodissociation and low koff from HbII/III, compared with those of HbI and Mb. Both isoforms behave very differently with regard to NO and O2 dynamics. Whereas the amplitude of geminate rebinding of O2 to HbI (38.5%) is similar to that of myoglobin (34.5%) in spite of different distal heme sites, it appears to be much larger for HbII/III (77%). The distal Tyr(B10) side chain present in HbII/III increases the energy barrier for ligand escape and participates in the stabilization of bound O2 and NO.
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http://dx.doi.org/10.1021/bi400745aDOI Listing
October 2013

Long-term analysis of the impact of longitudinal barriers on motorway safety.

Accid Anal Prev 2013 Oct 2;59:443-51. Epub 2013 Jul 2.

Université de Lyon, F-69622 Lyon, France; IFSTTAR UMRESTTE UMR_T 9406, Université Lyon 1, France. Electronic address:

The objective of this study was to assess the influence of longitudinal barriers located on the median strips and hard shoulders of toll motorways on crash severity in vehicles running off the roadway. The study was based on crashes involving injury and property damage only, recorded from 1996 to 2010 on a French toll motorway network of about 2000 km. In run-off from the roadway onto the hard shoulder, injury risk was halved by a longitudinal barrier. A specific one-sided W-beam guardrail ("GS4") appeared to be the best solution for cars, and even for LUVs and trucks. This does not affect the advisability of specific guardrails for bridges or of concrete barriers, when narrow working widths are required. In run-off onto median strips, a specific guardrail ("GS2") appeared to be the most efficient, followed by the three other metal guardrails currently installed. Concrete barriers, however, are much more effective in preventing complete crossing of the median, which is uncommon and mainly involves trucks, but often with very serious consequences. Longitudinal barriers make an important contribution to highway-user safety, providing a "forgiving" infrastructure in the event of a vehicle going off the road, provided that there are very few motorized two-wheel vehicles using the roadway.
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http://dx.doi.org/10.1016/j.aap.2013.06.024DOI Listing
October 2013

Picosecond binding of the His ligand to four-coordinate heme in cytochrome c': a one-way gate for releasing proximal NO.

J Am Chem Soc 2013 Feb 14;135(8):3248-54. Epub 2013 Feb 14.

Laboratoire d'Optique et Biosciences, INSERM, Ecole Polytechnique, 91128 Palaiseau Cedex, France.

We provide a direct demonstration of a "kinetic trap" mechanism in the proximal 5-coordinate heme-nitrosyl complex (5c-NO) of cytochrome c' from Alcaligenes xylosoxidans (AXCP) in which picosecond rebinding of the endogenous His ligand following heme-NO dissociation acts as a one-way gate for the release of proximal NO into solution. This demonstration is based upon picosecond transient absorption changes following NO photodissociation of the proximal 5c-NO AXCP complex. We have determined the absolute transient absorption spectrum of 4-coordinate ferrous heme to which NO rebinds with a time constant τ(NO) = 7 ps (k(NO) = 1.4 × 10(11) s(-1)) and shown that rebinding of the proximal histidine to the 4-coordinate heme takes place with a time constant τ(His) = 100 ± 10 ps (k(His) = 10(10) s(-1)) after the release of NO from the proximal heme pocket. This rapid His reattachment acts as a one-way gate for releasing proximal NO by precluding direct proximal NO rebinding once it has left the proximal heme pocket and requiring NO rebinding from solution to proceed via the distal heme face.
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http://dx.doi.org/10.1021/ja312140fDOI Listing
February 2013

Risk factors for injury accidents among moped and motorcycle riders.

Accid Anal Prev 2012 Nov 2;49:5-11. Epub 2010 Oct 2.

UMRESTTE, UMR T9405, INRETS, Université de Lyon, 25 Avenue François Mitterrand, 69675 Bron Cedex, F-69003, France.

Objective: To study and quantify the effect of factors related to the riders of powered two-wheelers on the risk of injury accident involvement.

Methodology: Based on national data held by the police from 1996 to 2005, we conducted a case-control study with responsibility for the accident as the event of interest. We estimated the odds ratios for accident responsibility. Making the hypothesis that the non-responsible riders in the study are representative of all the riders on the road, we thus identified risk factors for being responsible for injury accidents. The studied factors are age, gender, helmet wearing, alcohol consumption, validity of the subject's driving licence and for how long it has been held, the trip purpose and the presence of a passenger on the vehicle. Moped and motorcycle riders are analyzed separately, adjusting for the main characteristics of the accident.

Results: For both moped and motorcycle riders, being male, not wearing a helmet, exceeding the legal limit for alcohol and travelling for leisure purposes increased the risk of accident involvement. The youngest and oldest users had a greater risk of accident involvement. The largest risk factor was alcohol, and we identified a dose-effect relationship between alcohol consumption and accident risk, with an estimated odds ratio of over 10 for motorcycle and moped riders with a BAC of 2 g/l or over. Among motorcycle users, riders without a licence had twice the risk of being involved in an accident than those holding a valid licence. However, the number of years the rider had held a licence reduced the risk of accident involvement. One difference between moped and motorcycle riders involved the presence of a passenger on the vehicle: while carrying a passenger increased the risk of being responsible for the accident among moped riders, it protected against this risk among motorcycle riders.

Conclusion: This analysis of responsibility has identified the major factors contributing to excess risk of injury accidents, some of which could be targeted by prevention programmes.
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http://dx.doi.org/10.1016/j.aap.2010.08.021DOI Listing
November 2012

Picosecond to second dynamics reveals a structural transition in Clostridium botulinum NO-sensor triggered by the activator BAY-41-2272.

ACS Chem Biol 2012 Dec 2;7(12):2046-54. Epub 2012 Oct 2.

Laboratoire d'Optique et Biosciences, INSERM U696, CNRS UMR 7645, Ecole Polytechnique, 91128 Palaiseau Cedex, France.

Soluble guanylate cyclase (sGC) is the mammalian endogenous nitric oxide (NO) receptor that synthesizes cGMP upon NO activation. In synergy with the artificial allosteric effector BAY 41-2272 (a lead compound for drug design in cardiovascular treatment), sGC can also be activated by carbon monoxide (CO), but the structural basis for this synergistic effect are unknown. We recorded in the unusually broad time range from 1 ps to 1 s the dynamics of the interaction of CO binding to full length sGC, to the isolated sGC heme domain β(1)(200) and to the homologous bacterial NO-sensor from Clostridium botulinum. By identifying all phases of CO binding in this full time range and characterizing how these phases are modified by BAY 41-2272, we show that this activator induces the same structural changes in both proteins. This result demonstrates that the BAY 41-2272 binding site resides in the β(1)(200) sGC heme domain and is the same in sGC and in the NO-sensor from Clostridium botulinum.
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http://dx.doi.org/10.1021/cb3003539DOI Listing
December 2012

The motorcyclist impact against a light vehicle: epidemiological, accidentological and biomechanic analysis.

Accid Anal Prev 2012 Nov 30;49:223-8. Epub 2012 Aug 30.

Laboratoire de Biomécanique Appliquée UMRT24 IFSTTAR, Université de la Méditerranée Faculté de Médecine Nord, Bd Pierre Dramard 13916, Marseille Cedex 20, France.

This paper summarizes the results obtained within the framework of the French PROMOTO Project (PROtection of the MOTOrcyclist). The aim of this project was to analyze the impact between a motorcycle and a light vehicle from an epidemiological, accidentological and biomechanical point of view. The results have made it possible to outline the most frequent accident configurations such as the "turn on the left" and the most common injuries sustained by motorized two-wheelers (head and trunk). The biomechanic analysis has enabled a better understanding of the kinematics involved in an impact between a motorized two-wheeler and a light vehicle in various accident configurations (chronology and speed impact). While it is well known that motorcyclists frequently receive life threatening injuries to the head, spine and torso, this paper has been able to observe specific injury mechanisms such as pelvis impacts against the vehicle fuel tank and hyper-extension of the neck due to head impact on passenger cars.
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http://dx.doi.org/10.1016/j.aap.2012.08.013DOI Listing
November 2012

Impacts of biological invasions: what's what and the way forward.

Trends Ecol Evol 2013 Jan 10;28(1):58-66. Epub 2012 Aug 10.

Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN 37996, USA.

Study of the impacts of biological invasions, a pervasive component of global change, has generated remarkable understanding of the mechanisms and consequences of the spread of introduced populations. The growing field of invasion science, poised at a crossroads where ecology, social sciences, resource management, and public perception meet, is increasingly exposed to critical scrutiny from several perspectives. Although the rate of biological invasions, elucidation of their consequences, and knowledge about mitigation are growing rapidly, the very need for invasion science is disputed. Here, we highlight recent progress in understanding invasion impacts and management, and discuss the challenges that the discipline faces in its science and interactions with society.
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http://dx.doi.org/10.1016/j.tree.2012.07.013DOI Listing
January 2013

Absorption band III kinetics probe the picosecond heme iron motion triggered by nitric oxide binding to hemoglobin and myoglobin.

J Phys Chem B 2012 Apr 19;116(13):4106-14. Epub 2012 Mar 19.

Laboratoire d'Optique et Biosciences, INSERM, Ecole Polytechnique, 91128 Palaiseau, France.

To study the ultrafast movement of the heme iron induced by nitric oxide (NO) binding to hemoglobin (Hb) and myoglobin (Mb), we probed the picosecond spectral evolution of absorption band III (∼760 nm) and vibrational modes (iron-histidine stretching, ν(4) and ν(7) in-plane modes) in time-resolved resonance Raman spectra. The time constants of band III intensity kinetics induced by NO rebinding (25 ps for hemoglobin and 40 ps for myoglobin) are larger than in Soret bands and Q-bands. Band III intensity kinetics is retarded with respect to NO rebinding to Hb and to Mb. Similarly, the ν((Fe-His)) stretching intensity kinetics are retarded with respect to the ν(4) and ν(7) heme modes and to Soret absorption. In contrast, band III spectral shift kinetics do not coincide with band III intensity kinetics but follows Soret kinetics. We concluded that, namely, the band III intensity depends on the heme iron out-of-plane position, as theoretically predicted ( Stavrov , S. S. Biopolymers 2004 , 74 , 37 - 40 ).
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http://dx.doi.org/10.1021/jp300849yDOI Listing
April 2012

Quaternary structure controls ligand dynamics in soluble guanylate cyclase.

J Biol Chem 2012 Feb 4;287(9):6851-9. Epub 2012 Jan 4.

Laboratoire d'Optique et Biosciences, INSERM U696, CNRS UMR 7645 Ecole Polytechnique, 91128 Palaiseau, France.

Soluble guanylate cyclase (sGC) is the mammalian endogenous nitric oxide (NO) receptor. The mechanisms of activation and deactivation of this heterodimeric enzyme are unknown. For deciphering them, functional domains can be overexpressed. We have probed the dynamics of the diatomic ligands NO and CO within the isolated heme domain β(1)(190) of human sGC by piconanosecond absorption spectroscopy. After photo-excitation of nitrosylated sGC, only NO geminate rebinding occurs in 7.5 ps. In β(1)(190), both photo-dissociation of 5c-NO and photo-oxidation occur, contrary to sGC, followed by NO rebinding (7 ps) and back-reduction (230 ps and 2 ns). In full-length sGC, CO geminate rebinding to the heme does not occur. In contrast, CO geminately rebinds to β(1)(190) with fast multiphasic process (35, 171, and 18 ns). We measured the bimolecular association rates k(on) = 0.075 ± 0.01 × 10(6) M(-1) · S(-1) for sGC and 0.83 ± 0.1 × 10(6) M(-1) · S(-1) for β(1)(190). These different dynamics reflect conformational changes and less proximal constraints in the isolated heme domain with respect to the dimeric native sGC. We concluded that the α-subunit and the β(1)(191-619) domain exert structural strains on the heme domain. These strains are likely involved in the transmission of the energy and relaxation toward the activated state after Fe(2+)-His bond breaking. This also reveals the heme domain plasticity modulated by the associated domains and subunit.
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http://dx.doi.org/10.1074/jbc.M111.299297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307277PMC
February 2012