Development of gene expression-based biomarkers of exposure to metals and pesticides in the freshwater amphipod Hyalella azteca

Ecological risk assessment (ERA) is a framework for monitoring risks of exposure and adverse effects of environmental stressors to populations or communities of interest. One tool of ERA is the biomarker, which is a characteristic of an organism that reliably indicates exposure to or effects of a stressor like chemical pollution. Traditional biomarkers which rely on characteristics at the tissue level and higher often detect only acute exposures to stressors. Sensitive molecular biomarkers may detect lower stressor levels than traditional biomarkers, which helps inform risk mitigation and restoration efforts before populations and communities are irreversibly affected. In this study I developed gene expression-based molecular biomarkers of exposure to metals and insecticides in the model toxicological freshwater amphipod Hyalella azteca. My goals were to not only create sensitive molecular biomarkers for these chemicals, but also to show the utility and versatility of H. azteca in molecular studies for toxicology and risk assessment. I sequenced and assembled the H. azteca transcriptome to identify reference and stress-response gene transcripts suitable for expression monitoring. I exposed H. azteca to sub-lethal concentrations of metals (cadmium and copper) and insecticides (DDT, permethrin, and imidacloprid). Reference genes used to create normalization factors were determined for each exposure using the programs BestKeeper, GeNorm, and NormFinder. Both metals increased expression of a nuclear transcription factor (Cnc), an ABC transporter (Mrp4), and a heat shock protein (Hsp90), giving evidence of general metal exposure signature. Cadmium uniquely increased expression of a DNA repair protein (Rad51) and increased Mrp4 expression more than copper (7-fold increase compared to 2-fold increase). Together these may be unique biomarkers distinguishing cadmium and copper exposures. DDT increased expression of Hsp90, Mrp4, and the immune response gene Lgbp. Permethrin increased expression of a cytochrome P450 (Cyp2j2) and decreased expression of the immune response gene Lectin-1. Imidacloprid did not affect gene expression. Unique biomarkers were seen for DDT and permethrin, but the genes studied were not sensitive enough to detect imidacloprid at the levels used here. I demonstrated that gene expression in H. azteca detects specific chemical exposures at sub-lethal concentrations, making expression monitoring using this amphipod a useful and sensitive biomarker for risk assessment of chemical exposure.

Task-based approach used on surfaces sampling strategy definition: the case of antineoplastic occupational exposure

Task-based approach implicates identifying all the tasks developed in each workplace aiming to refine the exposure characterization. The starting point of this approach is the recognition that only through a more detailed and comprehensive understanding of tasks is possible to understand, in more detail, the exposure scenario. In addition allows also the most suitable risk management measures identification. This approach can be also used when there is a need of identifying the workplace surfaces for sampling chemicals that have the dermal exposure route as the most important. In this case is possible to identify, through detail observation of tasks performance, the surfaces that involves higher contact (frequency) by the workers and can be contaminated. Identify the surfaces to sample when performing occupational exposure assessment to antineoplasic agents. Surfaces selection done based on the task-based approach.

Twenty years of Hendra virus: laboratory submission trends and risk factors for infection in horses

Hendra virus (HeV) was first described in 1994 in an outbreak of acute and highly lethal disease in horses and humans in Australia. Equine cases continue to be diagnosed periodically, yet the predisposing factors for infection remain unclear. We undertook an analysis of equine submissions tested for HeV by the Queensland government veterinary reference laboratory over a 20-year period to identify and investigate any patterns. We found a marked increase in testing from July 2008, primarily reflecting a broadening of the HeV clinical case definition. Peaks in submissions for testing, and visitations to the Government HeV website, were associated with reported equine incidents. Significantly differing between-year HeV detection rates in north and south Queensland suggest a fundamental difference in risk exposure between the two regions. The statistical association between HeV detection and stockhorse type may suggest that husbandry is a more important risk determinant than breed per se. The detection of HeV in horses with neither neurological nor respiratory signs poses a risk management challenge for attending veterinarians and laboratory staff, reinforcing animal health authority recommendations that appropriate risk management strategies be employed for all sick horses, and by anyone handling sick horses or associated biological samples.

EXPOSURE TO EXTREME HEAT EVENTS AND CHRONIC RESPIRATORY DISEASES AMONG A NATIONALLY REPRESENTATIVE SAMPLE OF THE UNITED STATES POPULATION

Previous studies have shown that extreme weather events are on the rise in response to our changing climate. Such events are projected to become more frequent, more intense, and longer lasting. A consistent exposure metric for measuring these extreme events as well as information regarding how these events lead to ill health are needed to inform meaningful adaptation strategies that are specific to the needs of local communities. Using federal meteorological data corresponding to 17 years (1997-2013) of the National Health Interview Survey, this research: 1) developed a location-specific exposure metric that captures individuals’ “exposure” at a spatial scale that is consistent with publicly available county-level health outcome data; 2) characterized the United States’ population in counties that have experienced higher numbers of extreme heat events and thus identified population groups likely to experience future events; and 3) developed an empirical model describing the association between exposure to extreme heat events and hay fever. This research confirmed that the natural modes of forcing (e.g., El Niño-Southern Oscillation), seasonality, urban-rural classification, and division of country have an impact on the number extreme heat events recorded. Also, many of the areas affected by extreme heat events are shown to have a variety of vulnerable populations including women of childbearing age, people who are poor, and older adults. Lastly, this research showed that adults in the highest quartile of exposure to extreme heat events had a 7% increased odds of hay fever compared to those in the lowest quartile, suggesting that exposure to extreme heat events increases risk of hay fever among US adults.

Contribute of the MYCOMIX project and future perspectives for Human Biomonitoring and health risk assessment in Portugal

There is a growing concern within public health about mycotoxin involvement in human diseases, namely those related to children. The MycoMix project (2012-2015), funded by the Portuguese Foundation for Science and Technology, gathered a multidisciplinary team aiming at answering several questions: 1) Are Portuguese children exposed daily to one or several mycotoxins through food? 2) Can this co-exposure affect children´s health? and 3) Are there interaction effect between mycotoxins? Mycomix results revealed that Portuguese children (< 3 years old, n=103) are exposed to multiple mycotoxins through food consumption. Cumulative risk assessment results revealed a potential health concern for the high percentiles of intake, specially for aflatoxins which are carcinogenic compounds. This fact assumes particular importance considering the interactive effects found in in vitro bioassays. These results highlight the need for a more accurate approach to assess the human exposure to mycotoxins6. Within the Mycomix project the assessment of mycotoxin exposure was based on calculations combining mycotoxin data in food with population data on food consumption. This approach does not consider some aspects as the inter-individual metabolism variation, the exposure through sources other than food and the heterogeneous distribution of mycotoxins in food. Exposure assessment of mycotoxins in Portuguese population through biomarkers is still missing and further studies are urgent to be developed. The European Human Biomonitoring Initiative (EHBMI), a proposal within the European Joint Programme, aims to advance the understanding of the extent of exposure to environmental chemicals across Europe and the impact on human health, by gathering national expertise in human biomonitoring domain. At national level Mycomix project uncovered the potential health risk of exposure of Portuguese children to multiple mycotoxins. The risk assessment expertise acquired within Mycomix, namely in analysis and toxicology of chemical mixtures, will be brought together as a contribute to EHBMI objectives.

Is there a health risk concerning the children´s consumption of cereal-based products? A cumulative mycotoxin risk assessment approach

Historically, the health risk of mycotoxins had been evaluated on the basis of single-chemical and single-exposure pathway scenarios. However, the co-contamination of foodstuffs with these compounds is being reported at an increasing rate and a multiple-exposure scenario for humans and vulnerable population groups as children is urgently needed. Cereals are among the first solid foods eaten by child and thus constitute an important food group of their diet. Few data are available relatively to early stages child´s exposure to mycotoxins through consumption of cereal-based foods. The present study aims to perform the cumulative risk assessment of mycotoxins present in a set of cereal-based foods including breakfast cereals (BC), processed cereal-based foods (PCBF) and biscuits (BT), consumed by children (1 to 3 years old, n=75) from Lisbon region, Portugal. Children food consumption and occurrence of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) in cereal-based foods were combined to estimate the mycotoxin daily intake, using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) and aflatoxin daily exposure. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (HQ, ratio between exposure and a reference dose). The concentration addition (CA) concept was used for the cumulative risk assessment of multiple mycotoxins. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. Main results revealed a significant health concern related to aflatoxins and especially aflatoxin M1 exposure according to the MoET and MoE values (below 10000), respectively. HQ and HI values for the remaining mycotoxins were below 1, revealing a low concern from a public health point of view. These are the first results on cumulative risk assessment of multiple mycotoxins present in cereal-based foods consumed by children. Considering the present results, more research studies are needed to provide the governmental regulatory bodies with data to develop an approach that contemplate the human exposure and, particularly, children, to multiple mycotoxins in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health.

Twenty years of Hendra virus: laboratory submission trends and risk factors for infection in horses

SUMMARY Hendra virus (HeV) was first described in 1994 in an outbreak of acute and highly lethal disease in horses and humans in Australia. Equine cases continue to be diagnosed periodically, yet the predisposing factors for infection remain unclear. We undertook an analysis of equine submissions tested for HeV by the Queensland government veterinary reference laboratory over a 20-year period to identify and investigate any patterns. We found a marked increase in testing from July 2008, primarily reflecting a broadening of the HeV clinical case definition. Peaks in submissions for testing, and visitations to the Government HeV website, were associated with reported equine incidents. Significantly differing between-year HeV detection rates in north and south Queensland suggest a fundamental difference in risk exposure between the two regions. The statistical association between HeV detection and stockhorse type may suggest that husbandry is a more important risk determinant than breed per se. The detection of HeV in horses with neither neurological nor respiratory signs poses a risk management challenge for attending veterinarians and laboratory staff, reinforcing animal health authority recommendations that appropriate risk management strategies be employed for all sick horses, and by anyone handling sick horses or associated biological samples.

Children exposure to indoor ultrafine particles in urban and rural school environments

Extended exposure to ultrafine particles (UFPs) may lead to consequences in children due to their increased susceptibility when compared to older individuals. Since children spend in average 8 h/day in primary schools, assessing the number concentrations of UFPs in these institutions is important in order to evaluate the health risk for children in primary schools caused by indoor air pollution. Thus, the purpose of this study was to assess and determine the sources of indoor UFP number concentrations in urban and rural Portuguese primary schools. Indoor and outdoor ultrafine particle (UFP) number concentrations were measured in six urban schools (US) and two rural schools (RS) located in the north of Portugal, during the heating season. The mean number concentrations of indoor UFPs were significantly higher in urban schools than in rural ones (10.4 × 10(3) and 5.7 × 10(3) pt/cm(3), respectively). Higher UFP levels were associated with higher squared meters per student, floor levels closer to the ground, chalk boards, furniture or floor covering materials made of wood and windows with double-glazing. Indoor number concentrations of ultrafine-particles were inversely correlated with indoor CO2 levels. In the present work, indoor and outdoor concentrations of UFPs in public primary schools located in urban and rural areas were assessed, and the main sources were identified for each environment. The results not only showed that UFP pollution is present in augmented concentrations in US when compared to RS but also revealed some classroom/school characteristics that influence the concentrations of UFPs in primary schools.

Psychosocial and occupational risk perception among health care workers: a Moroccan multicenter study.

International audience

Establishing continental sovereignty in Africa: risk and opportunity in financial integration - lessons for Africa from a legal perspective

This thesis identifies and defines the new African sovereignty. It establishes a modern sovereignty in Africa hatched from the changing nature of sovereignty in which countries come together at various levels or grades of partial surrender of national sovereignty in order to work closer together for their mutual advantage and benefit. To this end, the narrative zooms in on the central issues within the realms of money matters whereby a new model of monetary sovereignty and monetary solutions is designed in an attempt to ease the recurring tensions and challenges of modern national sovereignty in the continent of Africa. As such, this discussion will offer a historical journey through the constitution of sovereignty, to the birth of the nation state and international public law. It develops the theory of the changing nature of sovereignty within the modern state and opens new lines of inquiry for Africa. In this regard, it draws from juxtaposing and mixing elements of regional and global financial integration as well as retaining national financial sovereignty features to form this new design which I dub continental sovereignty. At its core, the thesis will deal with the legal aspects that stem from the co-mingling of legal systems of nation states and communities at the regional and global levels within the context of financial integration. The argument is that the rule of law remains sacrosanct in monetary management. Effective financial integration is the result of properly structured and managed legal frameworks with robust laws and institutions whether at a national, regional or global level. However, the thesis reveals that in order to avoid undermining the progress of Africa’s financial integration project, any solution for Africa must be immersed within a broader global solution where development issues are addressed and resolved and Africa can form a more central part in all relevant international discussion fora. The work will expound these issues by applying them within a regional and global context, with the state of affairs in Africa forming the nucleus. This application consequently presents the six key themes of the thesis which will be considered therein. They are: a.) regional advantage: which exploits the possibilities of deeper and further financial integration between smaller communal arrangements; b.) regional risk and exposure: the extent to which this deeper form of financial integration can spiral out of control if effected too quickly and too ambitiously; c.) global advantage: which considers the merits of global financial integration and the influence exerted by financial laws on the global financial architecture; d.) global risk and exposure: which considers the challenges of global financial integration especially within the background of the Global Financial Crisis 2007-2008; e.) African challenge: which considers the extent to which this analysis impacts the African economic and financial integration agenda; and f.) development challenge: which examines the extent to which global development issues impact the African solution (continental sovereignty) and the need for any solution for the continent to be roped into a broader global solution within which Africa can form an important part. Even though the thesis requests an optimistic undertone on the progress made so far, it unearths the African problem of multiple national sovereignty and multiple overlapping regional sovereignty constituted as the ‘spaghetti bowl’ dilemma. As such, the unique contribution to knowledge on financial integration in Africa can be echoed in these words: Africa‘s financial integration agenda has had little success in authenticating a systematic and dependable legal framework for monetary management. Efforts made have been incomplete, substandard, and not carefully followed through particularly reflected in the impuissant nature of the judicial enforcement mechanisms. Thus, the thesis argues that, any meaningful answer to the problems dogging the continent is inter alia deeply entrenched within a new form of cooperative monetary sovereignty. In other words, the thesis does not prescribe the creation of new laws; rather it advocates the effective enforcement of existing laws.

Incidence of Chronic and Other Knee Pain in Relation to Occupational Risk Factors in a Large Working Population.

International audience

Lateral epicondylitis and physical exposure at work? A review of prospective studies and meta-analysis

International audience

Wellbeing and occupational risk perception among health care workers: a multicenter study in Morocco and France

International audience

Evaluation of ergonomic physical risk factors in a truck manufacturing plant: case study in SCANIA Production Angers

International audience

Prevalence, severity and risk factors of allergic disorders among people in south India.

Background: Allergic disorders are not usually life-threatening conditions but they impair the person’s ability to function. It thus adversely affects the psychological wellbeing and quality of life. These implications of allergic disorders can be minimized if strategies are planned for its early identification followed by appropriate interventions. Objectives: To find out the prevalence and risk factors of allergic disorders. Methods: Data was collected by house to house survey among participants aged 18 years and above using a standardized allergy assessment questionnaire. Results: Mean age of the 400 participants was 42.8±14.7 years. Majority 105(26.2%) were in the age group 36 to 45 years. Majority were females 287(71.7%) and were house wives 217(54.2%). Majority of participants were of upper socio economic class 98(44.7%) out of 219 and majority were from urban areas 326(81.5%). The prevalence of allergy among participants was found to be 115(28.7%). Out of these 115, 37(32.2%) had possibility of allergy, 60(52.2%) had probability of allergy and the rest 18(15.6%) had very high likelihood for allergy. People residing in semi urban areas had increased risk of allergy (p=0.024) than those from urban areas. The prevalence of asthma was 30(7.5%) and skin allergy was 23(5.8%). Most common precipitating factors for allergy were dust exposure 103(25.8%) followed by seasonal changes 71(17.8%). Family history of allergy was associated with allergy among participants (p<0.001). Usage of firewood was associated with symptoms of respiratory allergy among participants (p=0.01). Conclusion: The study revealed some important determinants of allergic disorders which have important implications to frame appropriate prevention and health educational strategies.