Absence Of Exposure Research Articles

Current Mathematical Models for Analyzing Anti-Malarial Antibody Data with an Eye to Malaria Elimination and Eradication

The last decade has witnessed a steady reduction of the malaria burden worldwide. With various countries targeting disease elimination in the near future, the popular parasite infection or entomological inoculation rates are becoming less and less informative of the underlying malaria burden due to a reduced number of infected individuals or mosquitoes at the time of sampling. To overcome such problem, alternative measures based on antibodies against specific malaria antigens have gained recent interest in malaria epidemiology due to the possibility of estimating past disease exposure in absence of infected individuals. This paper aims then to review current mathematical models and corresponding statistical approaches used in antibody data analysis. The application of these models is illustrated with three data sets from Equatorial Guinea, Brazilian Amazonia region, and western Kenyan highlands. A brief discussion is also carried out on the future challenges of using these models in the context of malaria elimination.

Chronic actinic dermatitis: A case report

Chronic actinic dermatitis (CAD) is a chronic eczematoid photodermatosis expressed more frequently in middle aged or older males. A variety of etiologies such as photoallergic, phototoxic, immunologic and metabolic factors have been postulated in CAD. It is initiated and clinically triggered with exposure to sunlight and artificial radiation. At the present time, photosensitive eczema (mild form), photosensitive dermatitis, persistent light reaction and actinic reticuloid (severe form) have been collected under the title of CAD. The basic components of this disease are a persistent, chronic, eczematous eruption in the absence of exposure to known photosensitizers; photosensitivity to UVA, and/or UVB, and/or visible light; and histology consistent with a chronic dermatitis with or without features of lymphoma. In this report, we presented a case with CAD due to its rarity.

Early Neonatal Bilirubin, Hematocrit, and Glucose-6-Phosphate Dehydrogenase Status

To document the patterns of bilirubin and hematocrit values among glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD-normal Nigerian neonates in the first week of life, in the absence of exposure to known icterogenic agents. The G6PD status of consecutive term and near-term neonates was determined, and their bilirubin levels and hematocrits were monitored during the first week of life. Infants were stratified into G6PD deficient, intermediate, and normal on the basis of the modified Beutler's fluorescent spot test. Means of total serum bilirubin (TSB) and hematocrits of the 3 groups of infants were compared. The 644 neonates studied comprised 353 (54.8%) boys and 291 (45.2%) girls and 540 (83.9%) term and 104 (16.1%) near-term infants. They consisted of 129 (20.0%) G6PD-deficient, 69 (10.7%) G6PD-intermediate, and 446 (69.3%) G6PD-normal neonates. The G6PD-deficient and G6PD-intermediate infants had higher mean TSB than their G6PD-normal counterparts at birth and throughout the first week of life (P < .001). Mean peak TSB levels were 14.1 (9.48), 10.2 (3.8), and 6.9 (3.3) mg/dL for G6PD-deficient, G6PD-intermediate, and G6PD-normal neonates, respectively. Peak TSB was attained on approximately day 4 in all 3 groups, and trends in TSB were similar. Mean hematocrits at birth were similar in the 3 G6PD groups. However, G6PD-deficient and -intermediate infants had higher declines in hematocrit, bilirubin levels, and need for phototherapy than G6PD-normal infants (P < .001). The G6PD-deficient and G6PD-intermediate neonates had a higher risk of neonatal hyperbilirubinemia and would therefore need greater monitoring in the first week of life, even without exposure to known icterogenic agents.

Efficacy of olive mill wastewater for protecting Bacillus thuringiensis formulation from UV radiations

The effectiveness of 10 low-cost UV-absorbers in protecting Bacillus thuringiensis subsp. kurstaki BLB1 toxins against inactivation by UV-A and UV-B irradiation was evaluated in this study. Among them, two by-products, molasses and olive mill wastewater (OMW) were selected for further studies. They were tested at different concentrations of 0.05, 0.1, 0.15 and 0.2% using the para-aminobenzoic acid (PABA) as a common UV protectant. Interestingly, addition of PABA and OMW to BLB1 formulations was found to be most effective in protecting BLB1 spores at 90.8 and 76.4% respectively and in preserving delta-endotoxin concentration at a level of 81.7 and 72.2%, respectively when used at a concentration of 0.2%. The lowest preserved spores (46.3%) and delta-endotoxin level (12.4%) was found using molasses. In contrast, spore count and delta-endotoxin concentration were completely reduced after an exposure of unprotected Bt strain BLB1 to UV radiations up to 96h. SDS-PAGE analysis of protected and unprotected samples revealed that delta-endotoxin bands (130, 65–70kDa) were conserved until 96h of UV exposure in presence of PABA or OMW compared with their disappearance in presence of molasses after 72h of exposure and their dramatically decline from 8h of exposure in unprotected mixture. A complete loss of larvicidal toxicity against Ephestia kuehniella was found after 24h of exposure in absence of any UV-absorber. Addition of OMW or PABA offered the highest levels of insecticidal activity with 63.2 and 74.7% of residual toxicity, respectively. Whereas, molasses addition, as UV protectant retained only 26.3% of residual activity after 96h of exposure. Therefore, addition of OMW by-product to Bt formulation may be a suitable alternative to others synthetic chemical compounds. OMW may also provided added value, be environmentally friendly and less hazardous, when used at low concentration.

Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

Individuals naturally exposed to Plasmodium falciparum lose clinical immunity after a prolonged lack of exposure. P. falciparum antigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity of P. falciparum antigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinical P. falciparum malaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document that P. falciparum antigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence of P. falciparum exposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack of P. falciparum exposure.

Acclimation and adaptation to common marine pollutants in the copepod Tigriopus californicus

Establishing water quality criteria using bioassays is complicated by variation in chemical tolerance between populations. Two major contributors to this variation are acclimation and adaptation, which are both linked to exposure history, but differ in how long their effects are maintained. Our study examines how tolerance changes over multiple generations of exposure to two common marine pollutants, copper (Cu) and tributyltin oxide (TBTO), in a sexually reproducing marine copepod, Tigriopus californicus. Lines of T. californicus were chronically exposed to sub-lethal levels of Cu and TBTO for 12 generations followed by a recovery period of 3 generations in seawater control conditions. At each generation, the average number of offspring produced and survived to 28d was determined and used as the metric of tolerance. Lines exposed to Cu and TBTO showed an overall increase in tolerance over time. Increased Cu tolerance arose by generation 3 in the chronically exposed lines and was lost after 3 generations in seawater control conditions. Increased TBTO tolerance was detected at generation 7 and was maintained even after 3 generations in seawater control conditions. It was concluded from this study that tolerance to Cu is consistent with acclimation, a quick gain and loss of tolerance. In contrast, TBTO tolerance is consistent with adaptation, in which onset of tolerance was delayed relative to an acclimation response and maintained in the absence of exposure. These findings illustrate that consideration of exposure history is necessary when using bioassays to measure chemical tolerance.

A unification of mediation and interaction: a 4-way decomposition.

The overall effect of an exposure on an outcome, in the presence of a mediator with which the exposure may interact, can be decomposed into 4 components: (1) the effect of the exposure in the absence of the mediator, (2) the interactive effect when the mediator is left to what it would be in the absence of exposure, (3) a mediated interaction, and (4) a pure mediated effect. These 4 components, respectively, correspond to the portion of the effect that is due to neither mediation nor interaction, to just interaction (but not mediation), to both mediation and interaction, and to just mediation (but not interaction). This 4-way decomposition unites methods that attribute effects to interactions and methods that assess mediation. Certain combinations of these 4 components correspond to measures for mediation, whereas other combinations correspond to measures of interaction previously proposed in the literature. Prior decompositions in the literature are in essence special cases of this 4-way decomposition. The 4-way decomposition can be carried out using standard statistical models, and software is provided to estimate each of the 4 components. The 4-way decomposition provides maximum insight into how much of an effect is mediated, how much is due to interaction, how much is due to both mediation and interaction together, and how much is due to neither.

Ovarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstrual Cycles and in the Absence of Exposure to Alkylating Agents

Journal of Women's HealthVol. 22, No. 12 EditorialOvarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstrual Cycles and in the Absence of Exposure to Alkylating AgentsSandra Gofinet PasotoSandra Gofinet PasotoSearch for more papers by this authorPublished Online:27 Nov 2013https://doi.org/10.1089/jwh.2013.4642AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Ovarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstrual Cycles and in the Absence of Exposure to Alkylating Agents." , 22(12), pp. 1003–1004FiguresReferencesRelatedDetails Volume 22Issue 12Dec 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Sandra Gofinet Pasoto.Ovarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstrual Cycles and in the Absence of Exposure to Alkylating Agents.Journal of Women's Health.Dec 2013.1003-1004.http://doi.org/10.1089/jwh.2013.4642Published in Volume: 22 Issue 12: November 27, 2013PDF download

Etxadi–Gangoiti scale: a proposal to evaluate the family contexts of two-year-old children†

This paper makes a proposal for the comprehensive assessment of the family context of children aged two years. It offers an updated resource based on recent research into the assessment of family contexts and their influence on children's psychological development. The proposal explores the following areas: Presence of learning materials; Potential for play; Stimulation of cognitive development; Stimulation of language development; Emotional expressiveness; Setting of limits and optimal frustration; Enhancement of self-esteem and autonomy; Observation of mother–child interactions; Father's involvement; Quality of non-parental care; Relations with the extended family and social support network; Stability of the child's social relationships; Relations with the school; Diversity of experiences; Absence of exposure to conflict; Absence of parental stress; and Quality of the physical context. The areas explored are grouped into three blocks: Stimulation of cognitive and linguistic development; Stimulation of socio-emotional development; and Organisation of the social context and physical environment.

The Relationship Between a Specific IgE Level and Asthma Outcomes: Results from the 2005-2006 National Health and Nutrition Examination Survey

Allergen exposure is associated with increased specific IgE (sIgE), and allergen exposure plus sensitization is predictive of asthma outcomes. However, it is not known if sIgE is predictive of asthma outcomes in the absence of exposure data. To investigate whether IgE to indoor allergens is predictive of and has a dose-response relationship with asthma emergency department (ED) visits and wheeze. In the 2005-2006 National Health and Nutrition Examination Survey, 351 children and 390 adults reported current asthma. Continuous sIgE to 9 indoor allergens were considered. Asthma morbidity in the past year was measured by wheezing. Health care utilization was defined as any asthma ED visits in the past year. Analyses were adjusted for race, age, education, poverty index ratio and (in adults) tobacco use. In children, ED visits were associated with cockroach (odds ratio [OR] 1.5 [95% CI, 1.1-2 .1), rat (OR 1.9 [95% CI, 1.2-2.8]), and Aspergillus (OR 1.6 [95% CI, 1.001-2.60]). Continuous Aspergillus (OR 1.5 [95% CI, 1.04-2.1), Alternaria (OR 1.4 [95% CI, 1.1-1.6]), and total IgE (OR 1.2 [95% CI, 1.1-1.4]) were associated with wheeze in children. Adult ED visits were associated with sIgE for dust mites (Dermatophagoides pteronyssinus OR 1.6 [95% CI, 1.3-2.1]; Dermatophagoides farinae OR 1.6 [95% CI, 1.3-1.9]), total IgE (OR 1.4 [95% CI, 1.04- 1.9]), and the sum of sIgEs (OR 1.6 [95% CI, 1.2-2.2]). Sensitization to particular indoor environmental allergens was found to be a risk factor for wheeze and asthma ED visits. These outcomes increased as the concentration of sIgE to these allergens increased.

Is it possible to do without the study of myocardial perfusion in 2013?

The analysis of myocardial perfusion is a key step in the cardiac MRI examination. In routine work, this exploration carried out at rest is based on the qualitative first pass study of gadolinium with an ECG-triggered saturation recovery bFFE sequence. In view of recent knowledge, the analysis of the myocardial perfusion under vasodilator stress may be carried out by scintigraphy or MRI, the latter benefiting from the absence of exposure to ionizing rays and a lower cost. Besides coronary disease, the perfusion sequence provides a rich semiology to compare with the clinics and the data from other sequences. Arterial Spin Labeling (ASL) is an alternative technique used in the animal to quantify myocardial perfusion.

Tolerant beekeepers display venom-specific functional IgG4 antibodies in the absence of specific IgE

Tolerant beekeepers display venom-specific functional IgG4 antibodies in the absence of specific IgE

Aggregation of Exposure Level and Probability into a Single Metric in Job-Exposure Matrices Creates Bias

Job-exposure matrices (JEMs) are often used in occupational epidemiological studies to provide an exposure estimate for a typical person in a 'job' during a particular time period. A JEM can produce exposure estimates on a variety of scales, such as (but not limited to) binary assessments of presence or absence of exposure, ordinal ranking of exposure level and frequency, and quantitative exposure estimates of exposure intensity and frequency. Specifically, one popular approach to construct a JEM, engendered in a Finnish job exposure matrix (FINJEM), provides a probability that a worker within an occupational group is exposed and an estimate of intensity of exposure among the exposed workers within this occupation. Often the product of the probability and intensity (aka level) is used to obtain the estimate of exposure for the epidemiological analyses. This procedure aggregates exposure across exposed and non-exposed individuals and the effect of this particular procedure on epidemiological analyses has never been studied. We developed a theoretical framework for understanding how these aggregate exposure estimates relate to true exposure (either unexposed or log-normally distributed for 'exposed'), assuming that there is no uncertainty about estimates of level and probability of exposure. Theoretical derivations show that multiplying occupation-specific exposure level and probability of non-zero exposure results in both systematic and differential measurement errors. Simulations demonstrated that under certain conditions bias in odds ratios in a cohort study away from the null are possible and that this bias is smaller when (a) arithmetic rather than geometric mean is used to assess exposure level and (b) exposure level and prevalence are positively correlated. We illustrate the potential impact of using the specified JEM in a simulation based on a case-control study of non-Hodgkin lymphoma and exposure to ionizing and non-ionizing radiation. Inflation of standard errors in the log-odds was observed as well as bias away from null for two out of three specific exposures/data structures. Overall, it is clear that influence of the phenomenon we studied on epidemiological results is complex and difficult to predict, being influenced a great deal by the structure of data. We recommend exploring the influence of JEMs that use the product of exposure level and probability in epidemiological analyses through simulations during planning of such studies to assess both the expected extent of the potential bias in risk estimates and impact on power. The SAS and R code required to implement such simulations are provided. All our calculations are either theoretical or based on simulated data.

Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke

Embryonic stem cells (ESCs) provide a valuable in vitro model for testing toxicity of chemicals and environmental contaminants including cigarette smoke. Mouse ESCs were acutely or chronically exposed to smoke components, cigarette smoke condensate (CSC), or cadmium, an abundant component of CSC, and then evaluated for their self-renewal, apoptosis, DNA damage and telomere function. Acute exposure of ESCs to high dose of CSC or cadmium increased DNA damage and apoptosis. Yet, ESCs exhibited a remarkable capacity to recover following absence of exposure. Chronic exposure of ESCs to low dose of CSC or cadmium resulted in shorter telomeres and DNA damage. Together, acute exposure of ESCs to CSC or cadmium causes immediate cell death and reduces pluripotency, while chronic exposure of ESCs to CSC or cadmium leads to DNA damage and telomere shortening. Notably, a sub-proportion of ESCs during passages is selected to resist to smoke-induced oxidative damage to telomeres.

Distribution of &lt;I&gt;Bemisia tabaci&lt;/I&gt; (Hemiptera: Aleyrodidae) Biotypes in North America After the Q Invasion

After the 2004 discovery of the Bemisia tabaci (Gennadius) (Hemiptera Aleyrodidae) Q biotype in the United States, there was a vital need to determine the geographical and host distribution as well as its interaction with the resident B biotype because of its innate ability to rapidly develop high-level insecticide resistance that persists in the absence of exposure. As part of a coordinated country-wide effort, an extensive survey of B. tabaci biotypes was conducted in North America, with the cooperation of growers, industry, local, state, and federal agencies, to monitor the introduction and distribution of the Q biotype. The biotype status of submitted B. tabaci samples was determined either by polymerase chain reaction amplification and sequencing of a mitochondrial cytochrome oxidase I small subunit gene fragment and characterization of two biotype discriminating nuclear microsatellite markers or esterase zymogram analysis. Two hundred and eighty collections were sampled from the United States, Bermuda, Canada, and Mexico during January 2005 through December 2011. Host plants were split between ornamental plant and culinary herb (67%) and vegetable and field crop (33%) commodities. The New World biotype was detected on field-grown tomatoes (Solanum lycopersicum L.) in Mexico (two) and in commercial greenhouses in Texas (three) and represented 100% of these five collections. To our knowledge, the latter identification represents the first report of the New World biotype in the United States since its rapid displacement in the late 1980s after the introduction of biotype B. Seventy-one percent of all collections contained at least one biotype B individual, and 53% of all collections contained only biotype B whiteflies. Biotype Q was detected in 23 states in the United States, Canada (British Columbia and Ontario territories), Bermuda, and Mexico. Forty-five percent of all collections were found to contain biotype Q in samples from ornamentals, herbs and a single collection from tomato transplants located in protected commercial horticultural greenhouses, but there were no Q detections in outdoor agriculture (vegetable or field crops). Ten of the 15 collections (67%) from Canada and a single collection from Bermuda contained biotype Q, representing the first reports of biotype Q for both countries. Three distinct mitochondrial haplotypes of B. tabaci biotype Q whiteflies were detected in North America Our data are consistent with the inference of independent invasions from at least three different locations. Of the 4,641 individuals analyzed from 517 collections that include data from our previous work, only 16 individuals contained genetic or zymogram evidence of possible hybridization of the Q and B biotypes, and there was no evidence that rare hybrid B-Q marker co-occurrences persisted in any populations.

Early Intervention with Oral Immunotherapy is a Promising Strategy for the Treatment of Peanut Allergy

RationalePeanut oral immunotherapy (OIT) causes desensitization, but long-term tolerance induction has not been shown and safety and adherence remain important concerns. We designed a clinical trial to test the hypothesis that early intervention (EI) improves the efficacy of peanut OIT without adversely affecting safety or adherence.MethodsForty peanut-sensitized children aged 9-36 months were enrolled within six months of their initial reaction, or if the peanut-specific IgE (psIgE) exceeded 5 kUA/L in the absence of exposure. All subjects underwent baseline oral peanut challenge and were randomized to receive low- or high-dose OIT. Peanut-specific immune responses were serially analyzed. We utilized our research database to compare demographic, safety, adherence, and immunologic data between the EI cohort and an ongoing, previously reported trial of OIT in older children (PMIT).ResultsCompared to the PMIT group, at enrollment subjects receiving EI had lower median age (30 mo vs. 58 mo) and psIgE levels (15 kUA/L vs. 87 kUA/L) [both p<0.0001]. EI subjects were approximately half as likely as PMIT subjects to have an allergic side effect (ASE) deemed “likely” or “possibly” related to OIT [RR 0.56 (95%CI 0.50-0.62), p<0.0001]. Study termination due to ASE occurred in 3/26 (11.5%) PMIT compared to 1/40 (2.5%) EI [p=0.29]. After one year, peanut skin test size decreased similarly in both groups, and psIgE levels remained stable.ConclusionsEarly intervention with OIT may enhance safety and targets young peanut-allergic children for treatment while their psIgE levels are low. This may lead to improved long term outcomes. RationalePeanut oral immunotherapy (OIT) causes desensitization, but long-term tolerance induction has not been shown and safety and adherence remain important concerns. We designed a clinical trial to test the hypothesis that early intervention (EI) improves the efficacy of peanut OIT without adversely affecting safety or adherence. Peanut oral immunotherapy (OIT) causes desensitization, but long-term tolerance induction has not been shown and safety and adherence remain important concerns. We designed a clinical trial to test the hypothesis that early intervention (EI) improves the efficacy of peanut OIT without adversely affecting safety or adherence. MethodsForty peanut-sensitized children aged 9-36 months were enrolled within six months of their initial reaction, or if the peanut-specific IgE (psIgE) exceeded 5 kUA/L in the absence of exposure. All subjects underwent baseline oral peanut challenge and were randomized to receive low- or high-dose OIT. Peanut-specific immune responses were serially analyzed. We utilized our research database to compare demographic, safety, adherence, and immunologic data between the EI cohort and an ongoing, previously reported trial of OIT in older children (PMIT). Forty peanut-sensitized children aged 9-36 months were enrolled within six months of their initial reaction, or if the peanut-specific IgE (psIgE) exceeded 5 kUA/L in the absence of exposure. All subjects underwent baseline oral peanut challenge and were randomized to receive low- or high-dose OIT. Peanut-specific immune responses were serially analyzed. We utilized our research database to compare demographic, safety, adherence, and immunologic data between the EI cohort and an ongoing, previously reported trial of OIT in older children (PMIT). ResultsCompared to the PMIT group, at enrollment subjects receiving EI had lower median age (30 mo vs. 58 mo) and psIgE levels (15 kUA/L vs. 87 kUA/L) [both p<0.0001]. EI subjects were approximately half as likely as PMIT subjects to have an allergic side effect (ASE) deemed “likely” or “possibly” related to OIT [RR 0.56 (95%CI 0.50-0.62), p<0.0001]. Study termination due to ASE occurred in 3/26 (11.5%) PMIT compared to 1/40 (2.5%) EI [p=0.29]. After one year, peanut skin test size decreased similarly in both groups, and psIgE levels remained stable. Compared to the PMIT group, at enrollment subjects receiving EI had lower median age (30 mo vs. 58 mo) and psIgE levels (15 kUA/L vs. 87 kUA/L) [both p<0.0001]. EI subjects were approximately half as likely as PMIT subjects to have an allergic side effect (ASE) deemed “likely” or “possibly” related to OIT [RR 0.56 (95%CI 0.50-0.62), p<0.0001]. Study termination due to ASE occurred in 3/26 (11.5%) PMIT compared to 1/40 (2.5%) EI [p=0.29]. After one year, peanut skin test size decreased similarly in both groups, and psIgE levels remained stable. ConclusionsEarly intervention with OIT may enhance safety and targets young peanut-allergic children for treatment while their psIgE levels are low. This may lead to improved long term outcomes. Early intervention with OIT may enhance safety and targets young peanut-allergic children for treatment while their psIgE levels are low. This may lead to improved long term outcomes.

Estimation of particulate mass and Mn exposure levels among welders

ObjectivesHistorical exposure estimates for welding-exposed workers are needed for studies evaluating the relationship between welding and neurologic or other health outcomes. The objective of this study was to develop and...

Absence of Exposure to Varicella Does Not Increase the Risk of Zoster

Absence of Exposure to Varicella Does Not Increase the Risk of Zoster

Integrated Testing Strategies for Toxicity Employing New and Existing Technologies

We have developed individual, integrated testing strategies (ITS) for predicting the toxicity of general chemicals, cosmetics, pharmaceuticals, inhaled chemicals, and nanoparticles. These ITS are based on published schemes developed previously for the risk assessment of chemicals to fulfil the requirements of REACH, which have been updated to take account of the latest developments in advanced in chemico modelling and in vitro technologies. In addition, we propose an ITS for neurotoxicity, based on the same principles, for incorporation in the other ITS. The technologies are deployed in a step-wise manner, as a basis for decision-tree approaches, incorporating weight-of-evidence stages. This means that testing can be stopped at the point where a risk assessment and/or classification can be performed, with labelling in accordance with the requirements of the regulatory authority concerned, rather than following a checklist approach to hazard identification. In addition, the strategies are intelligent, in that they are based on the fundamental premise that there is no hazard in the absence of exposure - which is why pharmacokinetic modelling plays a key role in each ITS. The new technologies include the use of complex, three-dimensional human cell tissue culture systems with in vivo-like structural, physiological and biochemical features, as well as dosing conditions. In this way, problems of inter-species extrapolation and in vitro/in vivo extrapolation are minimised. This is reflected in the ITS placing more emphasis on the use of volunteers at the whole organism testing stage, rather than on existing animal testing, which is the current situation.

The Ige-Binding Self-Antigens Tubulin-Α and HLA-DR-Α are Overexpressed in Lesional Skin of Atopic Eczema Patients

Background: Atopic eczema is the most common chronic, relapsing, inflammatory skin disorder with an atopic background. Previous studies have shown that IgE-mediated reactivity to self-antigens plays a role in the pathogenesis of the disease. However, the expression of self-antigens associated with atopic eczema in the lesional skin is poorly investigated.Aim of the study: This study was aimed to show that IgE-binding self antigens are over-expressed in atopic eczema lesions. Methods: Tubulin-α and HLA-DR-α, two recently described self-antigens, were stained by immunohistochemistry in skin specimens from chronic and acute atopic eczema lesions, unaffected skin from the same patients or skin from healthy controls.Results: The expression of tubulin-α and HLA-DR-α is up-regulated in atopic eczema lesions compared to nonlesional or healthy skin and correlates with the number of infiltrating immune cells and the degree of inflammation.Conclusion: Upregulation of IgE-binding self-antigens in lesional skin of atopic eczema patients might further promote the existing inflammation and induce exacerbations of the disease in the absence of exposure to environmental allergens.