Determination of no-observed effect level (NOEL)-biomarker equivalents to interpret biomonitoring data for organophosphorus pesticides in children

<p>Abstract</p> <p>Background</p> <p>Environmental exposure to organophosphorus pesticides has been characterized in various populations, but interpretation of these data from a health risk perspective remains an issue. The current paper proposes biological reference values to help interpret biomonitoring data related to an exposure to organophosphorus pesticides in children for which measurements of alkylphosphate metabolites are available.</p> <p>Methods</p> <p>Published models describing the kinetics of malathion and chlorpyrifos in humans were used to determine no-observed effect level – biomarker equivalents for methylphosphates and ethylphosphates, respectively. These were expressed in the form of cumulative urinary amounts of alkylphosphates over specified time periods corresponding to an absorbed no-observed effect level dose (derived from a published human exposure dose) and assuming various plausible exposure scenarios. Cumulative amounts of methylphosphate and ethylphosphate metabolites measured in the urine of a group of Quebec children were then compared to the proposed biological reference values.</p> <p>Results</p> <p>From a published no-observed effect level dose for malathion and chlorpyrifos, the model predicts corresponding oral biological reference values for methylphosphate and ethylphosphate derivatives of 106 and 52 nmol/kg of body weight, respectively, in 12-h nighttime urine collections, and dermal biological reference values of 40 and 32 nmol/kg of body weight. Out of the 442 available urine samples, only one presented a methylphosphate excretion exceeding the biological reference value established on the basis of a dermal exposure scenario and none of the methylphosphate and ethylphosphate excretion values were above the obtained oral biological reference values, which reflect the main exposure route in children.</p> <p>Conclusion</p> <p>This study is a first step towards the development of biological guidelines for organophophorus pesticides using a toxicokinetic modeling approach, which can be used to provide a health-based interpretation of biomonitoring data in the general population.</p

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Trend and status of air quality at three different monitoring stations in the Klang Valley, Malaysia

Over the last decades, the development of the Klang Valley (Malaysia), as an urban commercial and industrial area, has elevated the risk of atmospheric pollutions. There are several significant sources of air pollutants which vary depending on the background of the location they originate from. The aim of this study is to determine the trend and status of air quality and their correlation with the meteorological factors at different air quality monitoring stations in the Klang Valley. The data of five major air pollutants (PM10, CO, SO2, O3, NO2) were recorded at the Alam Sekitar Sdn Bhd (ASMA) monitoring stations in the Klang Valley, namely Petaling Jaya (S1), Shah Alam (S2) and Gombak (S3). The data from these three stations were compared with the data recorded at Jerantut, Pahang (B), a background station established by the Malaysian Department of Environment. Results show that the concentrations of CO, NO2 and SO2 are higher at Petaling Jaya (S1) which is due to influence of heavy traffic. The concentrations of PM10 and O3, however, are predominantly related to regional tropical factors, such as the influence of biomass burning and of ultra violet radiation from sunlight. They can, though, also be influenced by local sources. There are relatively stronger inter-pollutant correlations at the stations of Gombak and Shah Alam, and the results also suggest that heavy traffic flow induces high concentrations of PM10, CO, NO2 and SO2 at the three sampling stations. Additionally, meteorological factors, particularly the ambient temperature and wind speed, may influence the concentration of PM10 in the atmosphere

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment

No role for quality scores in systematic reviews of diagnostic accuracy studies

BACKGROUND: There is a lack of consensus regarding the use of quality scores in diagnostic systematic reviews. The objective of this study was to use different methods of weighting items included in a quality assessment tool for diagnostic accuracy studies (QUADAS) to produce an overall quality score, and to examine the effects of incorporating these into a systematic review. METHODS: We developed five schemes for weighting QUADAS to produce quality scores. We used three methods to investigate the effects of quality scores on test performance. We used a set of 28 studies that assessed the accuracy of ultrasound for the diagnosis of vesico-ureteral reflux in children. RESULTS: The different methods of weighting individual items from the same quality assessment tool produced different quality scores. The different scoring schemes ranked different studies in different orders; this was especially evident for the intermediate quality studies. Comparing the results of studies stratified as "high" and "low" quality based on quality scores resulted in different conclusions regarding the effects of quality on estimates of diagnostic accuracy depending on the method used to produce the quality score. A similar effect was observed when quality scores were included in meta-regression analysis as continuous variables, although the differences were less apparent. CONCLUSION: Quality scores should not be incorporated into diagnostic systematic reviews. Incorporation of the results of the quality assessment into the systematic review should involve investigation of the association of individual quality items with estimates of diagnostic accuracy, rather than using a combined quality score

Global Intraurban Intake Fractions for Primary Air Pollutants from Vehicles and Other Distributed Sources

We model intraurban intake fraction (iF) values for distributed ground-level emissions in all 3646 global cities with more than 100,000 inhabitants, encompassing a total population of 2.0 billion. For conserved primary pollutants, population-weighted median, mean, and interquartile range iF values are 26, 39, and 14-52 ppm, respectively, where 1 ppm signifies 1 g inhaled/t emitted. The global mean urban iF reported here is roughly twice as large as previous estimates for cities in the United States and Europe. Intake fractions vary among cities owing to differences in population size, population density, and meteorology. Sorting by size, population-weighted mean iF values are 65, 35, and 15 ppm, respectively, for cities with populations larger than 3, 0.6-3, and 0.1-0.6 million. The 20 worldwide megacities (each &gt;10 million people) have a population-weighted mean iF of 83 ppm. Mean intraurban iF values are greatest in Asia and lowest in land-rich high-income regions. Country-average iF values vary by a factor of 3 among the 10 nations with the largest urban populations

Identification of a new European rabbit IgA with a serine-rich hinge region

<div><p>In mammals, the most striking IgA system belongs to Lagomorpha. Indeed, 14 IgA subclasses have been identified in European rabbits, 11 of which are expressed. In contrast, most other mammals have only one IgA, or in the case of hominoids, two IgA subclasses. Characteristic features of the mammalian IgA subclasses are the length and amino acid sequence of their hinge regions, which are often rich in Pro, Ser and Thr residues and may also carry Cys residues. Here, we describe a new IgA that was expressed in New Zealand White domestic rabbits of <i>IGHV</i>a1 allotype. This IgA has an extended hinge region containing an intriguing stretch of nine consecutive Ser residues and no Pro or Thr residues, a motif exclusive to this new rabbit IgA. Considering the amino acid properties, this hinge motif may present some advantage over the common IgA hinge by affording novel functional capabilities. We also sequenced for the first time the IgA14 CH2 and CH3 domains and showed that IgA14 and IgA3 are expressed.</p></div